Honours Projects School of Science and Health 3610 Bachelor of Medical Science (Honours) 3611 Bachelor of Science (Honours) 4657 Bachelor of Health Science (Honours) 2015 Congratulations on your great success so far in your undergraduate studies! You have been selected to receive this information amongst only a few students who may qualify to continue their studies by undertaking an Honours project in Science, Medical Science, or Health Science. This booklet will list available projects for the intake at the beginning of 2015 in the School of Science and Health. Please note that the projects listed may be on Campbelltown, Hawkesbury, Penrith, Parramatta campus or at external facilities. Further, some of the project areas listed will allow more than one Honours project. After you have browsed through the booklet and if you are interested in starting Honours, here is what you need to do next: 1. Attend one of the Honours information sessions. At this session you will receive more information about the Honours program and the application process. The sessions will be a great opportunity to meet supercvisors and current Honours students. 2. Please contact the supervisors listed in the booklet where you might be interested to undertake your Honours studies in (note that it is a good idea to keep your options open and have at least 3-4 choices as depending on demand not every student may get their first choice of projects); make and appointment with those supervisors and ask them all you need to know about the project. st 3. Fill in the application on line by 31 January 2015 at the following link: https://applyonline.uws.edu.au/connect/webconnect. Entry Requirements: You will need to have completed a Bachelors degree or be about to complete it. You will need to have achieved a threshold Admission Average Mark (AAM) equal to or above the minimum of 65. You must have organised a supervisory panel and an outline of the proposed research topic. To ensure your applications are processed well before the commencement of Autumn session, students are encouraged to submit their applications as early as possible. Late applications will not be accepted. If you would like to know more about the Honours program itself please check out the website: http://future.uws.edu.au/future_students_home/honours and our school website: http://www.uws.edu.au/ssh/school_of_science_and_health/honours If there are any further questions you need answered, please do not hesitate to contact [email protected] or 02 9685-9934 Kind Regards, Sabine Piller Academic Course Advisor Honours (Science; Medical Science) Kylie Steel Academic Course Advisor Honours (Health Science) Graham Jones Director of Academic Program (Science; Medical Science; Health Science) 2 Directory Physical Sciences - Condensed Matter Physics - Other Physical Sciences Chemical Sciences - Analytical Chemistry - Inorganic Chemistry - Macromolecular & Materials Chemistry - Medicinal & Biomolecular Chemistry - Physical Chemistry (incl Structural) Environmental Sciences - Environmental Science & Management Biological Sciences - Biochemistry & Cell Biology - Ecology - Evolutionary Biology - Genetics - Microbiology - Physiology - Plant Biology - Zoology Agricultural and Veterinary Sciences - Crop & Pasture Production Engineering - Food Science - Materials Engineering Technology - Medical Biotechnology Medical and Health Sciences - Medical Biochemistry & Metabolomics - Clinical Sciences - Complementary & Alternative Medicine - Human Movement and Sports Science - Immunology - Medical Microbiology - Neurosciences - Oncology & Carcinogensis - Paediatrics & Reproductive Medicine - Medical Physiology - Public Health & Health Services - Other Medical & Health Sciences Education - Curriculum & Pedagogy Page 4 Page 5 Page 19 Page 27 Page 28 Page 43 Page 55 Page 80 Page 94 Page 115 Page 116 Page 122 Page 123 Page 147 Page 162 Page 165 Page 171 Page 186 Page190 Page 193 Page 203 Page 204 Page 206 Page 207 Page 209 Page 217 Page 218 Page 220 Page 221 Page 226 Page 240 Page 262 Page 290 Page 292 Page 294 Page 311 Page 314 Page 317 Page 319 Page 339 Page 341 Page 342 3 Physical Sciences Including: Condensed Matter Physics Other Physical Sciences 4 Condensed Matter Physics 5 Field of Research: Title of Project: 0204 0299 0306 Advanced Water Signal Suppression in in vivo NMR Spectroscopy Supervisor: Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Co-supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Campus project is offered and conducted: Campbelltown Background (max 500 words) In mammalian tissue, the common metabolites (e.g., tCr and NAA) used in NMR based disease diagnosis are present in concentrations several orders of magnitude smaller than water. Consequently, in vivo proton NMR spectra are overwhelmed by the extremely strong water signal, thereby preventing accurate detection of metabolites and thus the diagnostic value is unreliable. In this study, advanced water signal suppression techniques will be developed for better detection of metabolites and thus more accurate NMR based disease diagnoses. (Would suit students interested in Biology/Chemistry/Medical Physics/MRI/NMR) Aim of Study: To build advanced water signal suppression techniques for in vivo NMR spectroscopy Methods: Nuclear Magnetic Resonance Spectroscopy Ethics Application Requirements: Not Applicable Key References: 1. S.W. Provencher, Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnetic Resonance in Medicine, 1993. 30(6): p. 672-679. 2. G. Zheng and W. S. Price. Solvent Signal Suppression in NMR. Prog.NMR Spectrosc. 56 (3): 267-288, 2010. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 6 Field of Research: Title of Project: 0204 0299 0304 Consequences of chronic neuroinflammation on the brain: implications on Alzheimer's disease Supervisor: Prof Gerald Muench Email: [email protected] Telephone: 4620 3216 Co-supervisor: Dr Erika Gyengesi Email: [email protected] Telephone: 4620 3723 Dr Tim-Stait-Gardner [email protected] 4620 3216 Prof William S Price [email protected] 4620 3336 Campus project is offered and conducted: Campbelltown Background (max 500 words) Epidemiological evidence shows that plant-derived foods with anti-inflammatory and anti-oxidant potential protect against Alzheimer’s disease (AD), but it is not clear which compounds are responsible for this positive effect. Activated, cytokine-overexpressing microglia are near-universal components of Aβ plaques at early and mid-stages during the progression of AD, and only decline in end-stage, dense core plaques. Activated microglia show close associations with tangle-bearing cholinergic neurons in AD. However, transgenic animal models of AD, which overexpressing mutant forms of presenilin, tau and amyloid precursor protein do not show the same variety of pro-inflammatory markers as human AD patients and develop a much weaker neuroinflammatory phenotype. To establish an animal model in which specific food compounds can be tested, we will use transgenic mice, which show chronic brain inflammation and develop progressive neurological deficits. We will monitor changes in their behavior, including a decline in cognitive functions. We will also investigate the underlying pathological changes, e.g. how chronic inflammation destroys nerve cells and their connections by using anatomical methods and MRI scans. Finally, we will investigate to what degree curcumin, a natural anti-oxidant and anti-inflammatory compound, can attenuate inflammation, prevent brain damage, and the loss of memory functions in our mice. We expect that our model will assist in the selection of potent candidate drugs, which can then be validated in clinical trials with Alzheimer patients. Aim of Study: The specific aims of this study are: 1. To study the effects of chronic neuroinflammation on the deterioration of memory and cognition in the GFAP-IL-6 overexpressing mice during their lifespan. The changes of the brain structure will be also examined by high resolution Magnetic Resonance Imaging (MRI). 2. To study the effects of neuroinflammation on the morphological structure of the basal forebrain cholinergic system and the interconnected areas using immunohistochemistry. 3. To investigate the effects of a high bioavailable preparation of the anti-inflammatory compound curcumin on brain inflammation, neurodegeneration and cognitive decline. Methods: Specific aim 1. To study the effects of chronic neuroinflammation on the deterioration of memory and cognition in the IL-6 overexpressing mice during their lifespan. Specific aim 2. To study the effects of neuroinflammation on the morphological structure of the basal forebrain cholinergic system and its interconnected areas. Specific aim 3. To investigate the effects of anti-inflammatory compound curcumin on brain inflammation, neurodegeneration and synaptic decline. Ethics Application Requirements: Animal Research Authority application has been approved by the UWS Animal Ethics committee to conduct animal research, as documented in Animal Research and Teaching Proposal Number: A10057; Title: Anatomical and behavioural studies of the rodent brain during neuroinflammation in IL6-GFAP mice; at the following site: Animal holdings - C Building 30 SoM animal holdings 7 Key References: 1. Ikegami, S. Behavioral impairment in radial-arm maze learning and acetylcholine content of the hippocampus and cerebral cortex in aged mice. Behav Brain Res 65, 103-111 (1994). 2. Heyser, C. J., Masliah, E., Samimi, A., Campbell, I. L. & Gold, L. H. Progressive decline in avoidance learning paralleled by inflammatory neurodegeneration in transgenic mice expressing interleukin 6 in the brain. Proc Natl Acad Sci U S A 94, 1500-1505 (1997). 3. Campbell, I. L. et al. Transgenic models to assess the pathogenic actions of cytokines in the central nervous system. Mol Psychiatry 2, 125-129 (1997). 4. Campbell, I. L. & Powell, H. C. Role of Cytokines in Demyelinating Disease Studied in Transgenic Mice. Methods 10, 462-477 (1996). 5. Campbell, I. L., Kay, T. W., Oxbrow, L. & Harrison, L. C. Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. J Clin Invest 87, 739-742, doi:10.1172/JCI115055 (1991). 6. Campbell, I. L., Eddleston, M., Kemper, P., Oldstone, M. B. & Hobbs, M. V. Activation of cerebral cytokine gene expression and its correlation with onset of reactive astrocyte and acute-phase response gene expression in scrapie. J Virol 68, 2383-2387 (1994). 7. Campbell, I. L. & Chiang, C. S. Cytokine involvement in central nervous system disease. Implications from transgenic mice. Ann N Y Acad Sci 771, 301-312 (1995). 8. Campbell, I. L. et al. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci U S A 90, 10061-10065 (1993). 9. Campbell, I. L. Structural and functional impact of the transgenic expression of cytokines in the CNS. Ann N Y Acad Sci 840, 83-96 (1998). 10. Fuller, S., Munch, G. & Steele, M. Activated astrocytes: a therapeutic target in Alzheimer's disease? Expert Rev Neurother 9, 1585-1594, doi:10.1586/ern.09.111 (2009). 11. Maczurek, A., Shanmugam, K. & Munch, G. Inflammation and the redox-sensitive AGE-RAGE pathway as a therapeutic target in Alzheimer's disease. Ann N Y Acad Sci 1126, 147-151, doi:10.1196/annals.1433.026 (2008). 12. Steele, M., Stuchbury, G. & Munch, G. The molecular basis of the prevention of Alzheimer's disease through healthy nutrition. Exp Gerontol 42, 28-36, doi:10.1016/j.exger.2006.06.002 (2007). 13. Huber, A., Stuchbury, G., Burkle, A., Burnell, J. & Munch, G. Neuroprotective therapies for Alzheimer's disease. Curr Pharm Des 12, 705-717 (2006). 14. Stuchbury, G. & Munch, G. Alzheimer's associated inflammation, potential drug targets and future therapies. J Neural Transm 112, 429-453, doi:10.1007/s00702-004-0188-x (2005). 15. Munch, G. et al. Microglial activation induces cell death, inhibits neurite outgrowth and causes neurite retraction of differentiated neuroblastoma cells. Exp Brain Res 150, 1-8, doi:10.1007/s00221-003-1389-5 (2003). 8 Field of Research: Title of Project: 0204 0303 0306 Supervisor: Decode Nature’s Way of Detoxification – NMR Studies on Dissolved Organic Matter in Australian Aquatic Systems Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Co-supervisor: Prof William S Price Campus project is offered and conducted: Email: [email protected] Telephone: 4620 3336 Campbelltown Background (max 500 words) Like ourselves, mother nature has many methods for detoxification. Dissolved organic matter (DOM) plays a major role in natural detoxification in aquatic systems. In fresh water, many harmful versions of heavy metals (e.g., methylmercury) latch onto DOM then are more likely broken down into harmless compounds by sunlight. In sea water, however, these nasty metal complexes tend to latch onto salt (i.e., sodium chloride) instead of DOM and therefore are far more likely accumulated through the food chain, according to studies by a US researcher. In this study, the key chemical components of the various DOM in Australian aquatic systems will be identified, their roles in the natural detoxification will be revealed, and environmental factors (e.g., salt) affecting the detoxification process will be identified. (Would suit students interested in Biology/Chemistry/NMR/Physics) Aim of Study: To unveil the role of each key chemical component of DOM in natural aquatic detoxification. Methods: Nuclear Magnetic Resonance Spectroscopy, Fluorescence Spectroscopy, Size Exclusion Chromatography Ethics Application Requirements: Not Applicable Nuclear Magnetic Resonance Spectroscopy, Fluorescence Spectroscopy, Size Exclusion Chromatography Key References: 1. G. Zheng and W.S. Price, Direct hydrodynamic radius measurement on dissolved organic matter in natural waters using diffusion NMR. Environ. Sci. Tech., 2012. 46(3): p. 1675-1680. 2. G. Zheng, T. Stait-Gardner, P.G. Anil Kumar, A.M. Torres, and W.S. Price, PGSTE-WATERGATE: An STE-based PGSE NMR sequence with excellent solvent suppression. J. Magn. Reson., 2008. 191: 159-163. 3. G. Zheng and W.S. Price, Solvent signal suppression in NMR. Prog. Nucl. Magn. Reson. Spec., 2010. 56: 267-288. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 9 Field of Research: Title of Project: 0204 0303 0304 0306 Expanding the Boundaries and Applications of Diffusion NMR Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Allan Torres Email: [email protected] Telephone: 4620 3459 Campus project is offered and conducted: Campbelltown Background (max 500 words) Diffusion NMR is routinely used to study various molecular properties, and interactions occurring in solution. This technique is also valuable in MRI as it can be used to probe microscopic structures in biological tissues. Recently, longlived singlet spin states have been used in NMR diffusion and diffusion-diffraction studies. Unlike regular spin coherences, singlet spin states have significantly longer lifetimes on the order of tens of seconds to a minute making it feasible to study extremely slowly diffusing molecules. In diffusion-diffraction studies, long lived singlet states can potentially be useful for probing structures with larger characteristic distances. In this project, the restricted diffusion of test molecules in glass and flexible silica capillaries will be investigated by utilising singlet spin states and various NMR coherences. The feasibility of performing NMR diffusion experiments in a single capillary with internal diameter of 10-200 micrometers will also be studied. (Would suit students interested in NMR/Physical Chemistry/Physics) Aim of Study: To characterise NMR diffusion in capillaries using various spin coherences and singlet spin states. Methods: Nuclear Magnetic Resonance Spectroscopy Ethics Application Requirements: Not Applicable Key References: 1. M. Carravetta and M.H. Levitt, Long-lived nuclear spin states in high-field solution NMR. J. Am. Chem. Soc. 126 (2004) 6228-6229. 2. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 3. N.N. Yadav, A.M. Torres and W.S. Price, NMR q-space imaging of macroscopic pores using singlet spin states. J. Magn. Reson. 204 (2010) 346-348. 4. A.M. Torres, B. Ghadirian and W.S. Price, Diffusion-diffraction using singlet spin states and various NMR coherences in a J-coupled AX spin system. RSC Advances 8 (2012) 3352-3360. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 10 Field of Research: Title of Project: 0204 0299 0304 0306 Investigating Biostructures using NMR/MRI Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Tim-Stait-Gardner Email: [email protected] Telephone: 4620 3114 Campus project is offered and conducted: Campbelltown Background (max 500 words) Biological tissue is not just an amorphous arrangement of cells. Indeed most tissue has an underlying structure composed of microscopic components as in muscle fibres or, as has more recently been realised, fibre tracts in brain tissue. Although the tracts might ultimately be macroscopic, they are composed of microscopic components. Such structures are not only involved in normal biological function, but also in diseased states, such as multiple sclerosis, epilepsy, and Alzheimer’s disease. Traditional techniques used to visualise such structures are not only limited in their application, but often these methods are invasive and tedious. In this project new NMR/MRI diffusion methods will be used to characterise tissue microstructure on a microscopic scale well below the resolution that is achievable using standard MRI sequences. In addition, the student would participate in the development of new NMR/MRI methods aimed at elucidating sample microstructure. (Would suit students interested in Biology/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To characterise a variety of tissue microstructures (mainly brain and muscle) and to participate in the development of new NMR techniques with this purpose. Methods: Nuclear Magnetic Resonance Spectroscopy and Imaging Ethics Application Requirements: May be necessary for some tissue samples. Key References: 1. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 2. S. Mori, J. Zhang, Principles of diffusion tensor imaging and its applications to basic neuroscience research, Neuron 51 (2006) 527-539. 3. P. Callaghan, Principles of Nuclear Magnetic Resonance Microscopy, Oxford University Press 1994. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 11 Field of Research: Title of Project: 0204 0299 0303 0306 Investigating Phantoms and Biostructures using NMR/MRI Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Tim-Stait-Gardner Email: [email protected] Telephone: 4620 3216 Dr Scott A Willis Campus project is offered and conducted: [email protected] 4620 3114 Campbelltown Background (max 500 words) Biological tissue is not just an amorphous arrangement of cells. Indeed most tissue has an underlying structure composed of microscopic components as in muscle fibres or, as has more recently been realised, fibre tracts in brain tissue. Although the tracts might ultimately be macroscopic, they are composed of microscopic components. Such structures are not only involved in normal biological function, but also in diseased states, such as multiple sclerosis, epilepsy, and Alzheimer’s disease. Traditional techniques used to visualise such structures are not only limited in their application, but often these methods are invasive and tedious. In this project new NMR/MRI diffusion methods will be used to characterise microstructure of suitable phantom (e.g., gels, capillaries) and tissue samples on a microscopic scale well below the resolution that is achievable using standard MRI sequences. In addition, the student would participate in the development of new NMR/MRI methods aimed at elucidating sample microstructure. (Would suit students interested in Biology/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To characterise a variety of microstructures in phantom samples (e.g., gels, capillaries) as well as tissues (e.g., brain, muscle) and to participate in the development of new NMR techniques with this purpose. Methods: Nuclear Magnetic Resonance Spectroscopy and Imaging Ethics Application Requirements: Not Applicable Key References: 1. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 2. S. Mori, J. Zhang, Principles of diffusion tensor imaging and its applications to basic neuroscience research, Neuron 51 (2006) 527-539. 3. P. Callaghan, Principles of Nuclear Magnetic Resonance Microscopy, Oxford University Press 1994. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 12 Field of Research: Title of Project: 0204 0299 0303 0306 Investigating Restricted Diffusion using NMR Techniques Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Bahman Ghadirian Email: [email protected] Telephone: 4620 3216 Campus project is offered and conducted: Campbelltown Background (max 500 words) Modelling self-diffusion in complicated geometries is of fundamental importance in many areas of science including medicine. Modelling diffusion-controlled reactions - which occur widely in chemical, and biochemical systems, and nuclear magnetic resonance diffusion experiments in bounded systems, provide many prominent examples of where such modelling is required. Using a simple cellular system as an example, a reacting species diffuses to the enzymatic membrane and then reacts in some way, being either transformed into a product, becoming bound to the surface or transported through the surface. The nature of the interaction at the surface determines the boundary conditions in the modelling. Presently only solutions for some simple geometries are available. This is a serious impediment as most real-world structures that chemical reactions occur in have complicated geometries. Thus, there is a need to develop techniques for modelling diffusive processes near surfaces which are applicable to different geometries and arbitrary boundary conditions. (Would suit students interested in Biology/Chemistry/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To develop theoretical and experimental method for investigating diffusion in restricted systems and studying their application. Methods: Analytical modelling and numerical computer programming in Mathcad or Matlab, and testing the models using NMR experiments. Ethics Application Requirements: Not Applicable Key References: 1. C. H. Neuman, J. Chem. Phys. 60, 4508 (1974). 2. S. D. Traytak and W. S. Price, J. Chem. Phys. 127, 184508 (2007). 3. G. A. Truskey, F. Yuan, and D. F. Katz, Transport Phenomena in Biological Systems. (Pearson, London, 2004). 4. W. S. Price, NMR Studies of Translational Motion. (Cambridge University Press, Cambridge, 2009). 5. D. G. Duffy, Mixed Boundary Value Problems. (Chapman & Hall / CRC, New York, 2008). 6. B. Ghadirian, A. M. Torres, N. N. Yadav, and W. S. Price. J. Chem. Phys. 138:094202-1-094202-11 (2013). This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 13 Field of Research: Title of Project: 0204 0301 0303 0306 Investigation of diffusive averaging and viscosity effects in bimodal polymer solutions Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Assoc. Prof. Gary Dennis [email protected] 9685 9939 Dr Scott A Willis [email protected] 4620 3114 Campus project is offered and conducted: Campbelltown Background (max 500 words) The most fundamental form of molecular transport is self-diffusion – the random motion of molecules – and measurements of which provide information on the size of the molecule as well as any influences from restrictions/obstructions (e.g., diffusion in a cell or porous rock) or aggregation processes (e.g., drug-binding). A powerful, versatile and non-invasive method for measuring self-diffusion is pulse gradient spin-echo (PGSE) nuclear magnetic resonance (NMR). However, measurements of self-diffusion in polydisperse systems (e.g., polymer solutions with different molecular weight polymers present or aggregating proteins) is complicated by diffusive averaging effects since the NMR signals are the same or overlapped. Studying diffusive averaging in bimodal polymer solutions is of great significance as synthetic (e.g., polystyrene) and natural (e.g., proteins) polymers are inherently polydisperse. In this project, diffusive averaging will be studied for different bimodal polymer solutions (i.e., two molecular weights or two types of polymers present) of either chemically identical polymers of different molecular weights or mixtures of chemically different polymers of different or similar molecular weights. Several types of polymers could be considered for this study. Measurements of the viscosity of bimodal and monomodal polymer solutions will help to elucidate the diffusive averaging processes. (Would suit students interested in Physical chemistry/Mathematics/NMR) Aim of Study: To use NMR diffusion measurements and viscosity measurements to develop better models for diffusive averaging phenomena. Methods: Viscometry and NMR diffusometry. Ethics Application Requirements: Not Applicable Key References: 1. Price, W. S., NMR Studies of Translational Motion. Cambridge University Press: New York, 2009. 2. Willis, S. A.; Dennis, G. R.; Zheng, G.; Price, W. S. Macromolecules 2010, 43, 7351-7356. 3. Willis, S. A.; Price, W. S.; Eriksson-Scott, I. K.; Zheng, G.; Dennis, G. R. J. Mol. Liq. 2012, 167, 110-114. 4. Callaghan, P. T.; Pinder, D. N. Macromolecules 1985, 18, 373-379. 14 Field of Research: Title of Project: 0204 1103 1112 0306 MRI-based Electron Density Mapping for Radiotherapy Treatment Planning Supervisor: Prof William S Price Email: Co-supervisor: Dr Stephen Bosi (UNE) Email: [email protected] Telephone: 4620 3336 Telephone: Other members of the Nanoscale Research Group Campus project is offered and conducted: Campbelltown Background (max 500 words) Radiation therapy is a recommended treatment for approximately half of cancer cases [Delaney et al 2005]. Accurate planning of radiation dose requires both a picture of a patient's tissues and a map of the "electron density" of these tissues, currently obtained using CT (or "CAT") scans which use ionising radiation. At present an electron density (ED) map derived from a CT of the patient is the minimum requirement for treatment planning (TP) for external beam radiotherapy. Magnetic resonance imaging (MRI) scans actually provide a clearer tissue image than CT scans (and without using ionising radiation), but traditional medical MRI methods cannot provide a density map – at least not at the present time. Development of a new method which allows MRI to be used to measure tissue composition AND density would eliminate the extra radiation dose of a CT scan and streamline treatment planning. (Would suit students interested in Biology/Chemistry/Medical Physics/NMR) Aim of Study: The aim is to develop a method allowing MRI scanners to provide a tissue density map which is required for accurate radiation dose planning for radiation therapy. Methods: MRI Experiments + Analysis Ethics Application Requirements: Not Applicable Key References: 1. Delaney G., Jacob S., Featherstone C. et al. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer 104 1129-1137 (2005). 2. Khan F.M. "The Physics of Radiation Therapy" - 3rd ed., Lippincott & Wilkins. Philadelphia USA, 2003. 3. Wu Y., Reese T.G., Cao H., et al. Bone Mineral Imaged In Vivo by 31P Solid State MRI of Human Wrists J. Magn. Reson. Imaging. 34, 623–633 (2011). This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 15 Field of Research: Title of Project: 0204 0299 0303 0306 NMR Simulation using Symbolic Algebra Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Tim-Stait-Gardner Email: [email protected] Telephone: 4620 3216 Campus project is offered and conducted: Campbelltown Background (max 500 words) Understanding spin-dynamics is of fundamental importance for NMR students. However, in many instances to understand such complicated theory we must resort to computer simulation, which turns boring memorization into exciting practice. Numerical and symbolic algebra simulation programs can be used for the development of new NMR pulse sequences. In this project students will perform NMR simulations based on a full understanding of spindynamics to enhance the development of new NMR methods (e.g. water suppression and diffusion measurements). Exact numerical simulations of NMR experiments are often required for the development of new techniques and for the extraction of structural and dynamic information from the spectra. (Would suit students interested in Mathematics/MRI/NMR/Physics) Aim of Study: In this project, user friendly liquid state NMR simulation software will be developed based on density matrix, product operator and quaternion theories by the use of symbolic algebra software (e.g. Mathematica, Maple). The newly developed software will be distributed around UWS to assist NMR teaching and scientific research. Methods: Nuclear Magnetic Resonance Spectroscopy and computer simulation. Ethics Application Requirements: Not Applicable Key References: 1. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 2. R.P.F. Kanters et al., A Computer-Algebra Application for the Description of NMR Experiments Using the ProductOperator Formalism, J. Magn. Reson. 101, 23-29, 1993. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 16 Field of Research: Title of Project: 0204 0303 0304 0306 Quantitative Composition-Flavour Relationships Supervisor: Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Co-supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Campus project is offered and conducted: Campbelltown Background (max 500 words) Have you ever thought about why different wines have different tastes? What is controlling the flavour? What chemicals contribute to the flavour generation process? Are these chemicals staying as monomers or forming assemblies in the wine? The results of this study will answer all these tricky questions. (Would suit students interested in Biology/Chemistry/NMR/Physics/Statistics/Wine tasting) Aim of Study: To build an NMR-based wine tasting machine Methods: Nuclear Magnetic Resonance Spectroscopy Pattern Recognition Ethics Application Requirements: Not Applicable Key References: 1. Hu, N., D. Wu, K. Cross, S. Burikov, T. Dolenko, S. Patsaeva, and D.W. Schaefer, Structurability: A collective measure of the structural differences in vodkas. Journal of Agricultural and Food Chemistry, 2010. 58(12): p. 73947401. 2. Polášková, P., J. Herszage, and S.E. Ebeler, Wine flavor: Chemistry in a glass. Chemical Society Reviews, 2008. 37(11): p. 2478-2489. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 17 Field of Research: Title of Project: 0204 0303 0304 0306 Studying Ice Nucleation Protein Motifs with NMR Diffusion Measurements Supervisor: Prof. William S. Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Scott A Willis Email: [email protected] Telephone: 4620 3114 Dr Allan Torres [email protected] 4620 3459 Dr Gang Zheng [email protected] 4620 3729 Campus project is offered and conducted: Campbelltown Background (max 500 words) Freeze tolerance is important for life that exists in low temperature environments. Protection strategies include the use of antifreeze proteins to prevent ice crystal growth or the use of ice nucleation proteins (INPs).1, 2 INPs initiate ice formation earlier so that the organism has a chance to respond to the freezing for thermal protection or could be used as a means of retrieving nutrients from plants.1 INPs are thought to bind to water molecules in a way that resembles an ice crystal3 such that further nucleation is promoted but the mechanism is not fully understood. As such a study of translational diffusion4 and hydration of these proteins in aqueous solutions at various temperatures is pertinent for understanding this and would be of interest for potential applications of these proteins. (Would suit students interested in Biology/Chemistry/NMR) Aim of Study: This project aims to investigate particular motifs common in INPs via NMR diffusion methods at various temperatures to determine if they are useful for ice nucleation. Methods: NMR Diffusion Experiments + Analysis Ethics Application Requirements: Not Applicable Key References: 4. Zachariassen, K. E., Kristiansen, E., Cryobiology, 2000, 41, 257 – 279. 5. Graether, S. P., Jia, Z., Biophysical Journal, 2001, 80, 1169 – 1173. 6. Green, R. L., Warren, G. L., Nature, 1985, 317, 645 – 648. 7. Price, W. S., NMR Studies of Translational Motion. Cambridge University Press: New York, 2009. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 18 Other Physical Sciences 19 Field of Research: Title of Project: 0204 0299 0304 Consequences of chronic neuroinflammation on the brain: implications on Alzheimer's disease Supervisor: Prof Gerald Muench Email: [email protected] Telephone: 4620 3216 Co-supervisor: Dr Erika Gyengesi Email: [email protected] Telephone: 4620 3723 Dr Tim-Stait-Gardner [email protected] 4620 3216 Prof William S Price [email protected] 4620 3336 Campus project is offered and conducted: Campbelltown Background (max 500 words) Epidemiological evidence shows that plant-derived foods with anti-inflammatory and anti-oxidant potential protect against Alzheimer’s disease (AD), but it is not clear which compounds are responsible for this positive effect. Activated, cytokine-overexpressing microglia are near-universal components of Aβ plaques at early and mid-stages during the progression of AD, and only decline in end-stage, dense core plaques. Activated microglia show close associations with tangle-bearing cholinergic neurons in AD. However, transgenic animal models of AD, which overexpressing mutant forms of presenilin, tau and amyloid precursor protein do not show the same variety of pro-inflammatory markers as human AD patients and develop a much weaker neuroinflammatory phenotype. To establish an animal model in which specific food compounds can be tested, we will use transgenic mice, which show chronic brain inflammation and develop progressive neurological deficits. We will monitor changes in their behavior, including a decline in cognitive functions. We will also investigate the underlying pathological changes, e.g. how chronic inflammation destroys nerve cells and their connections by using anatomical methods and MRI scans. Finally, we will investigate to what degree curcumin, a natural anti-oxidant and anti-inflammatory compound, can attenuate inflammation, prevent brain damage, and the loss of memory functions in our mice. We expect that our model will assist in the selection of potent candidate drugs, which can then be validated in clinical trials with Alzheimer patients. Aim of Study: The specific aims of this study are: 1. To study the effects of chronic neuroinflammation on the deterioration of memory and cognition in the GFAP-IL-6 overexpressing mice during their lifespan. The changes of the brain structure will be also examined by high resolution Magnetic Resonance Imaging (MRI). 2. To study the effects of neuroinflammation on the morphological structure of the basal forebrain cholinergic system and the interconnected areas using immunohistochemistry. 3. To investigate the effects of a high bioavailable preparation of the anti-inflammatory compound curcumin on brain inflammation, neurodegeneration and cognitive decline. Methods: Specific aim 1. To study the effects of chronic neuroinflammation on the deterioration of memory and cognition in the IL-6 overexpressing mice during their lifespan. Specific aim 2. To study the effects of neuroinflammation on the morphological structure of the basal forebrain cholinergic system and its interconnected areas. Specific aim 3. To investigate the effects of anti-inflammatory compound curcumin on brain inflammation, neurodegeneration and synaptic decline. Ethics Application Requirements: Animal Research Authority application has been approved by the UWS Animal Ethics committee to conduct animal research, as documented in Animal Research and Teaching Proposal Number: A10057; Title: Anatomical and behavioural studies of the rodent brain during neuroinflammation in IL6-GFAP mice; at the following site: Animal holdings - C Building 30 SoM animal holdings 20 Key References: 16. Ikegami, S. Behavioral impairment in radial-arm maze learning and acetylcholine content of the hippocampus and cerebral cortex in aged mice. Behav Brain Res 65, 103-111 (1994). 17. Heyser, C. J., Masliah, E., Samimi, A., Campbell, I. L. & Gold, L. H. Progressive decline in avoidance learning paralleled by inflammatory neurodegeneration in transgenic mice expressing interleukin 6 in the brain. Proc Natl Acad Sci U S A 94, 1500-1505 (1997). 18. Campbell, I. L. et al. Transgenic models to assess the pathogenic actions of cytokines in the central nervous system. Mol Psychiatry 2, 125-129 (1997). 19. Campbell, I. L. & Powell, H. C. Role of Cytokines in Demyelinating Disease Studied in Transgenic Mice. Methods 10, 462-477 (1996). 20. Campbell, I. L., Kay, T. W., Oxbrow, L. & Harrison, L. C. Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. J Clin Invest 87, 739-742, doi:10.1172/JCI115055 (1991). 21. Campbell, I. L., Eddleston, M., Kemper, P., Oldstone, M. B. & Hobbs, M. V. Activation of cerebral cytokine gene expression and its correlation with onset of reactive astrocyte and acute-phase response gene expression in scrapie. J Virol 68, 2383-2387 (1994). 22. Campbell, I. L. & Chiang, C. S. Cytokine involvement in central nervous system disease. Implications from transgenic mice. Ann N Y Acad Sci 771, 301-312 (1995). 23. Campbell, I. L. et al. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci U S A 90, 10061-10065 (1993). 24. Campbell, I. L. Structural and functional impact of the transgenic expression of cytokines in the CNS. Ann N Y Acad Sci 840, 83-96 (1998). 25. Fuller, S., Munch, G. & Steele, M. Activated astrocytes: a therapeutic target in Alzheimer's disease? Expert Rev Neurother 9, 1585-1594, doi:10.1586/ern.09.111 (2009). 26. Maczurek, A., Shanmugam, K. & Munch, G. Inflammation and the redox-sensitive AGE-RAGE pathway as a therapeutic target in Alzheimer's disease. Ann N Y Acad Sci 1126, 147-151, doi:10.1196/annals.1433.026 (2008). 27. Steele, M., Stuchbury, G. & Munch, G. The molecular basis of the prevention of Alzheimer's disease through healthy nutrition. Exp Gerontol 42, 28-36, doi:10.1016/j.exger.2006.06.002 (2007). 28. Huber, A., Stuchbury, G., Burkle, A., Burnell, J. & Munch, G. Neuroprotective therapies for Alzheimer's disease. Curr Pharm Des 12, 705-717 (2006). 29. Stuchbury, G. & Munch, G. Alzheimer's associated inflammation, potential drug targets and future therapies. J Neural Transm 112, 429-453, doi:10.1007/s00702-004-0188-x (2005). 30. Munch, G. et al. Microglial activation induces cell death, inhibits neurite outgrowth and causes neurite retraction of differentiated neuroblastoma cells. Exp Brain Res 150, 1-8, doi:10.1007/s00221-003-1389-5 (2003). 21 Field of Research: Title of Project: 0204 0299 0306 Advanced Water Signal Suppression in in vivo NMR Spectroscopy Supervisor: Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Co-supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Campus project is offered and conducted: Campbelltown Background (max 500 words) In mammalian tissue, the common metabolites (e.g., tCr and NAA) used in NMR based disease diagnosis are present in concentrations several orders of magnitude smaller than water. Consequently, in vivo proton NMR spectra are overwhelmed by the extremely strong water signal, thereby preventing accurate detection of metabolites and thus the diagnostic value is unreliable. In this study, advanced water signal suppression techniques will be developed for better detection of metabolites and thus more accurate NMR based disease diagnoses. (Would suit students interested in Biology/Chemistry/Medical Physics/MRI/NMR) Aim of Study: To build advanced water signal suppression techniques for in vivo NMR spectroscopy Methods: Nuclear Magnetic Resonance Spectroscopy Ethics Application Requirements: Not Applicable Key References: 3. S.W. Provencher, Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnetic Resonance in Medicine, 1993. 30(6): p. 672-679. 4. G. Zheng and W. S. Price. Solvent Signal Suppression in NMR. Prog.NMR Spectrosc. 56 (3): 267-288, 2010. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 22 Field of Research: Title of Project: 0204 0299 0304 0306 Investigating Biostructures using NMR/MRI Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Tim-Stait-Gardner Email: [email protected] Telephone: 4620 3114 Campus project is offered and conducted: Campbelltown Background (max 500 words) Biological tissue is not just an amorphous arrangement of cells. Indeed most tissue has an underlying structure composed of microscopic components as in muscle fibres or, as has more recently been realised, fibre tracts in brain tissue. Although the tracts might ultimately be macroscopic, they are composed of microscopic components. Such structures are not only involved in normal biological function, but also in diseased states, such as multiple sclerosis, epilepsy, and Alzheimer’s disease. Traditional techniques used to visualise such structures are not only limited in their application, but often these methods are invasive and tedious. In this project new NMR/MRI diffusion methods will be used to characterise tissue microstructure on a microscopic scale well below the resolution that is achievable using standard MRI sequences. In addition, the student would participate in the development of new NMR/MRI methods aimed at elucidating sample microstructure. (Would suit students interested in Biology/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To characterise a variety of tissue microstructures (mainly brain and muscle) and to participate in the development of new NMR techniques with this purpose. Methods: Nuclear Magnetic Resonance Spectroscopy and Imaging Ethics Application Requirements: May be necessary for some tissue samples. Key References: 4. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 5. S. Mori, J. Zhang, Principles of diffusion tensor imaging and its applications to basic neuroscience research, Neuron 51 (2006) 527-539. 6. P. Callaghan, Principles of Nuclear Magnetic Resonance Microscopy, Oxford University Press 1994. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 23 Field of Research: Title of Project: 0204 0299 0303 0306 Investigating Phantoms and Biostructures using NMR/MRI Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Tim-Stait-Gardner Email: [email protected] Telephone: 4620 3216 Dr Scott A Willis Campus project is offered and conducted: [email protected] 4620 3114 Campbelltown Background (max 500 words) Biological tissue is not just an amorphous arrangement of cells. Indeed most tissue has an underlying structure composed of microscopic components as in muscle fibres or, as has more recently been realised, fibre tracts in brain tissue. Although the tracts might ultimately be macroscopic, they are composed of microscopic components. Such structures are not only involved in normal biological function, but also in diseased states, such as multiple sclerosis, epilepsy, and Alzheimer’s disease. Traditional techniques used to visualise such structures are not only limited in their application, but often these methods are invasive and tedious. In this project new NMR/MRI diffusion methods will be used to characterise microstructure of suitable phantom (e.g., gels, capillaries) and tissue samples on a microscopic scale well below the resolution that is achievable using standard MRI sequences. In addition, the student would participate in the development of new NMR/MRI methods aimed at elucidating sample microstructure. (Would suit students interested in Biology/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To characterise a variety of microstructures in phantom samples (e.g., gels, capillaries) as well as tissues (e.g., brain, muscle) and to participate in the development of new NMR techniques with this purpose. Methods: Nuclear Magnetic Resonance Spectroscopy and Imaging Ethics Application Requirements: Not Applicable Key References: 4. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 5. S. Mori, J. Zhang, Principles of diffusion tensor imaging and its applications to basic neuroscience research, Neuron 51 (2006) 527-539. 6. P. Callaghan, Principles of Nuclear Magnetic Resonance Microscopy, Oxford University Press 1994. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 24 Field of Research: Title of Project: 0204 0299 0303 0306 Investigating Restricted Diffusion using NMR Techniques Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Bahman Ghadirian Email: [email protected] Telephone: 4620 3216 Campus project is offered and conducted: Campbelltown Background (max 500 words) Modelling self-diffusion in complicated geometries is of fundamental importance in many areas of science including medicine. Modelling diffusion-controlled reactions - which occur widely in chemical, and biochemical systems, and nuclear magnetic resonance diffusion experiments in bounded systems, provide many prominent examples of where such modelling is required. Using a simple cellular system as an example, a reacting species diffuses to the enzymatic membrane and then reacts in some way, being either transformed into a product, becoming bound to the surface or transported through the surface. The nature of the interaction at the surface determines the boundary conditions in the modelling. Presently only solutions for some simple geometries are available. This is a serious impediment as most real-world structures that chemical reactions occur in have complicated geometries. Thus, there is a need to develop techniques for modelling diffusive processes near surfaces which are applicable to different geometries and arbitrary boundary conditions. (Would suit students interested in Biology/Chemistry/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To develop theoretical and experimental method for investigating diffusion in restricted systems and studying their application. Methods: Analytical modelling and numerical computer programming in Mathcad or Matlab, and testing the models using NMR experiments. Ethics Application Requirements: Not Applicable Key References: 7. C. H. Neuman, J. Chem. Phys. 60, 4508 (1974). 8. S. D. Traytak and W. S. Price, J. Chem. Phys. 127, 184508 (2007). 9. G. A. Truskey, F. Yuan, and D. F. Katz, Transport Phenomena in Biological Systems. (Pearson, London, 2004). 10. W. S. Price, NMR Studies of Translational Motion. (Cambridge University Press, Cambridge, 2009). 11. D. G. Duffy, Mixed Boundary Value Problems. (Chapman & Hall / CRC, New York, 2008). 12. B. Ghadirian, A. M. Torres, N. N. Yadav, and W. S. Price. J. Chem. Phys. 138:094202-1-094202-11 (2013). This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 25 Field of Research: Title of Project: 0204 0299 0303 0306 NMR Simulation using Symbolic Algebra Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Tim-Stait-Gardner Email: [email protected] Telephone: 4620 3216 Campus project is offered and conducted: Campbelltown Background (max 500 words) Understanding spin-dynamics is of fundamental importance for NMR students. However, in many instances to understand such complicated theory we must resort to computer simulation, which turns boring memorization into exciting practice. Numerical and symbolic algebra simulation programs can be used for the development of new NMR pulse sequences. In this project students will perform NMR simulations based on a full understanding of spindynamics to enhance the development of new NMR methods (e.g. water suppression and diffusion measurements). Exact numerical simulations of NMR experiments are often required for the development of new techniques and for the extraction of structural and dynamic information from the spectra. (Would suit students interested in Mathematics/MRI/NMR/Physics) Aim of Study: In this project, user friendly liquid state NMR simulation software will be developed based on density matrix, product operator and quaternion theories by the use of symbolic algebra software (e.g. Mathematica, Maple). The newly developed software will be distributed around UWS to assist NMR teaching and scientific research. Methods: Nuclear Magnetic Resonance Spectroscopy and computer simulation. Ethics Application Requirements: Not Applicable Key References: 3. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 4. R.P.F. Kanters et al., A Computer-Algebra Application for the Description of NMR Experiments Using the ProductOperator Formalism, J. Magn. Reson. 101, 23-29, 1993. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 26 Chemical Sciences Including: Analytical Chemistry Inorganic Chemistry Macromolecular & Materials Chemistry Medicinal & Biomolecular Chemistry Physical Chemistry (incl. Structural) 27 Analytical Chemistry 28 Title of Project: A fat lot of good: direct analysis of lipids by TLC-MS (FOR Code/s): 030101, 030108, 030405 Supervisor: David Harman Co-supervisor: Jens Coorssen Contact: [email protected] Contact: [email protected] Location of Project: Campbelltown Campus, School of Medicine Project Background: Lipids are fatty, waxy, or oily substances that the body uses for energy and structure. In fact, the walls of the cells in our body are composed largely of a double layer of a type of lipid called a phospholipid. It was previously thought the biological role of lipids was confined to membrane composition, energy storage, thermal insulation and as a dietary source of fat soluble vitamins. However, recently it was discovered that cells use lipids to communicate with each other. Furthermore, lipids are involved in immune system function, tissue inflammation and affect reproduction, metabolism and blood pressure. As a consequence, medical science is now engaged in an intense search for lipid biomarkers (indicators of disease) in order to allow early intervention in otherwise serious illnesses. It is therefore important to determine which types of lipids and how much of each are present in various types of body tissues. This Honours research project is focussed upon the development of methods to identify lipids directly after their separation, using state-of-the art instrumentation. Aim of Study: The main objective is to optimise the analysis of lipids using an established high performance thin layer chromatography (HPTLC) method1 coupled directly to mass spectrometry (MS). The hypothesis is that extraction conditions for different lipid species need to be optimised to achieve high quality, quantitative analyses at high detection sensitivity. Methods: A mixture of phospholipids of known composition will be separated using an established HPTLC technique. Identification of each resolved lipid species will be undertaken by electrospray ionisation MS (ESI-MS) via direct sampling from the TLC plate (Fig. 1) using the Camag TLC-MS interface (Fig. 2). Resolution of parallel standards will enable identification of lipid species as well as quantification of lipids in the test lanes. Methods will be developed to achieve detection, identification and quantification of different lipid species. Finally, the researcher will apply the method to quantitative evaluation of a native tissue extract, thus demonstrating that a ‘lipidome’ analysis is possible using HPTLC-MS. Ethics Application Requirements: No ethics approvals will be required. Key References: 1. M.A. Churchward, D. Brandman, T. Rogasevskaia, and J.R. Coorssen J. Chem. Biol. 2008, 1, 79-87. 2. H. Park, Y. Zhou and C.E. Costello J. Lipid Res. 2014, 55, 773-781. 2. M.L. Dória, C. Z. Cotrim, C. Simões, B. Macedo , P. Domingues, M.R. Domingues and L.A. Helguero J. Cell. Physiol. 2013, 228, 457–468. 3. J. Sherma J. AOAC Internat. 2012, 95, 992-1009 (review). 29 Title of Project: Characterizing polysaccharides for a better health (FOR Code/s): Medicinal and Biomolecular Chemistry - Characterisation of biological macromolecules (030403) Macromolecular and Materials Chemistry - Physical Chemistry of Materials (030304) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Prof. Kelvin Chan Email: [email protected] Location of Project: Parramatta Project Background Polysaccharides are a major and key component of our diet (starch typically represents 50 % of our energy). Glucomannan is a polysaccharide obtained from Konjac and popular to prepare for example jellies in different Asian countries.[1] Glucomannans have health benefits, as dietary fibers, against for example type II diabetes and obesity. However, the reasons for these benefits are not known at the molecular level. It is thus necessary to characterize glucomannans at the molecular level. Galactomannnans are used as viscosifier in the food industry and other fields. They have similarities in chemical composition to the glucomannans: their characterisation is more advanced but tedious, time-consuming and still plagued by a number of uncertainties.[2] The molecular structure of complex polysaccharides and their molecular motion can be understood through the characterisation by solid-state NMR [3]. Solid-state NMR will be applied to the glucomannans and galactomannans: this characterization is possible without any modification of the sample (no dissolution or any type of modification is necessary). We also have recently showed that (free-solution) capillary electrophoresis can separate polysaccharides according to their composition [4]: the method is new, easy, fast and is applied for the first time to glucomannans and galactomannans. Aim of Study: To characterize ‘real’ glucomannans and galactomannans samples developing new capillary electrophoresis and NMR spectroscopy methods, for applications as healthier food. Methods: Solid-state NMR spectroscopy, Capillary electrophoresis. Ethics Application Requirements: Not applicable Key References: [1] M Chua, K Chan, TJ Hocking, PA Williams, CJ Perry, TC Baldwin, Methodologies for the extraction and analysis of konjac glucomannan from corms of Amorphophallus konjac K. Koch. Carbohydrate Polymers, 2012, 87, 22022210 [2] MA Pollard, R Kelly, PA Fischer, EJ Windhab, B Eder, R Amado, Investigation of molecular weight distribution of LBG galactomannan for flours prepared from individual seeds, mixtures, and commercial samples. Food Hydrocolloids 2008, 22, 1596-1606 [3] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386 [4] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 30 Title of Project: Photo-oxidation of sugars and polysaccharides for their characterization by capillary electrophoresis (FOR Code/s): Organic Chemistry, Free radical chemistry (030301) Macromolecular and Materials Chemistry not elsewhere classified (030399) Analytical Chemistry - Instrumental Methods (excl. Immunological and Bioassay Methods) (030105) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Christopher Fellows Email: [email protected] Telephone: 6773 2470 Location of Project: Parramatta Project Background Carbohydrates make up most of the living world around us. Their identification and quantification is generally sought after in many fields such as food and beverage analysis, plant analysis, fermentation studies and metabolism studies. Current analysis methods are not well adapted to the complexity of polysaccharides and the mixtures of carbohydrates derived from them. We have shown that free-solution capillary electrophoresis offers the possibility of simple and robust separations for monosaccharides (such as from plant fibers) [1] or polysaccharides (such as gellan gums [2] and chitosan [3]). The method has a high potential, but the sensitivity of the detection is relatively low for many important polysaccharides such as starch, glucomannans, galactomannans or chitosan. Monosaccharide detection is possible, and highly sensitive through a photo-oxidation process taking place directly in the capillary window. The aim of this project is to apply this photo-oxidation to key polysaccharides chitosan, starch, glucomannans and galactomannans and compare the results to polyol models such as poly(vinyl alcohol). The influence of the addition of photo-oxidant, such as a radical photo-initiator,[4] will be studied, exploring the possibilities of this breakthrough in detection sensitivity. Aim of Study: To better understand the photo-oxidation of sugars and to improve the detection of sugars and polysaccharides with capillary electrophoresis. Methods: Capillary electrophoresis, Photochemistry, Computational chemistry. Ethics Application Requirements: Not applicable Key References: [1] JD Oliver, M Gaborieau, EF Hilder, P Castignolles, Simple and robust determination of monosaccharides in plant fibers in complex mixtures by capillary electrophoresis and high performance liquid chromatography. Journal of Chromatography A, 2013, 1291, 179-186 [2] DL Taylor, CJ Ferris, AR Maniego, P Castignolles, M in het Panhuis, M Gaborieau, Characterization of gellan gum by capillary electrophoresis. Australian Journal of Chemistry, 2012, 55, 1156-1164 [3] M Mnatsakanyan, JJ Thevarajah, RS Roi, A Lauto, M Gaborieau, P Castignolles, Separation of chitosan by degree of acetylation using simple free solution capillary electrophoresis. Analytical and Bioanalytical Chemistry 2013, 405, 6373-6378 [4] JD Oliver, AA Rosser, CM Fellows, Y Guillaneuf, JL Clement, M Gaborieau, P Castignolles, Understanding and improving direct UV detection of monosaccharides and disaccharides in free solution capillary electrophoresis. Analytica Chimica Acta 2014, 809, 183 31 Title of Project: Towards high quality bioplastics (FOR Code/s): Macromolecular and Materials Chemistry – Synthesis of Materials (030306) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Aurelia Charlot Email: [email protected] Location of Project: Parramatta Project Background It is desirable to replace materials derived from oil, such as current plastics, by new ones derived from renewable resources such as cellulose or galactomannans. Cellulose is a significant waste from agriculture, while galactomannans like guar gums are an additive used in the food industry whose resources are largely under-used [1,2]. This is due to the poor intrinsic mechanical properties of these polysaccharides as well as their high sensitivity to moisture. These polysaccharides are often chemically modified to adjust performance to the level of current plastics. Polysaccharides consist of molecules with different types of saccharide units (glucose, galactose, mannose), different molecular weights and different topologies: linear chains or branched ones. The chemical modification improves the properties but also adds to the complexity of the molecules. The elucidation of their structure is needed for the scientific design of bioplastics. We collaborate with Dr Aurelia Charlot and Prof Etienne Fleury (INSA, Lyon, France) to answer these fundamental questions. This project has a strong potential to lead to industrial collaborations. Aim of Study: To characterise and assess potential bioplastics derived from cellulose or galactomannans. With solidstate NMR [3] we will reveal the interplay between molecular structure and molecular motions, and explore the crucial role of moisture. We will use capillary electrophoresis (in the critical conditions) [4] to separate compounds with different compositions and different degrees of modification. Methods: Capillary electrophoresis, Solid-state NMR spectroscopy. Ethics Application Requirements: Not applicable Key References: [1] C Lacroix, E Sultan, E Fleury, A Charlot, Functional galactomannan platform from convenient esterification in imidazolium-based ionic liquids. Polymer Chemistry 2012, 3, 538-46 [2] G Mangiante, P Alcouffe, B Burdin, M Gaborieau, E Zeno, M Petit-Conil, J Bernard, A Charlot, E Fleury, Green nondegrading approach to alkyne-functionalized cellulose fibers and biohybrids thereof: synthesis and mapping of the derivatization. Biomacromolecules 2013, 14, 254-63 [3] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386 [4] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 32 Title of Project: Characterization of pH-responsive polymers to better understand controlled polymerization (FOR Code/s): Analytical Chemistry – Separation Science (030108) Macromolecular and Materials Chemistry – Polymerisation Mechanisms (030305) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Franck d’Agosto Email: [email protected] Location of Project: Parramatta Project Background pH-responsive polymers see their solubility in water greatly affected by pH. They are commonly used to stabilize colloids. The team of Prof. Bernadette Charleux and Dr Franck d’Agosto (University Lyon 1, France) developed a technology to control the polymerization of a variety of monomers in emulsion [1]. This process relies on the use of stable radical, nitroxides. The visit to UWS of Emilie Groison, PhD student enrolled in Lyon, France showed the potential of the capillary electrophoresis method we develop in our group to separate the pH-responsive stabilizer. Aim of Study: The aim of the project is investigate the potential of capillary electrophoresis [2-3] to separate these complex samples. The samples are synthesized in Lyon. The project consists in separating them and characterizing them to finally explore the mechanism of the nitroxide-mediated polymerization process. Methods: Capillary electrophoresis. Ethics Application Requirements: Not applicable Key References: [1] E Groison, S Brusseau, F D’Agosto, S Magnet, R Inoubli, L Couvreur, B Charleux, Well-defined amphiphilic block copolymer nanoobjects via nitroxide-mediated emulsion polymerization. ACS Macro Letters, 2012, 1, 47-51 [2] M Gaborieau, TJ Causon, Y Guillaneuf, EF Hilder, P Castignolles, Molecular weight and tacticity of oligoacrylates by capillary electrophoresis-mass spectrometry. Australian Journal of Chemistry 2010, 63, 1219-26 [3] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 33 Title of Project: From smart polymers to anticancer drug carriers (FOR Code/s): Inorganic chemistry – Bioniorganic Chemistry (030201) Macromolecular and Materials Chemistry - Synthesis of Materials (030306) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Feng Li Email: [email protected] Telephone: 9987 Location of Project: Parramatta Project Background Smart polymers such as hyperbranched poly(acrylic acid) and chitosan are being tested for drug delivery. Our colleagues in Marseilles, France, can control the synthesis to obtain a range of branched poly(acrylic acid)s. These polyacrylates are also ‘smart’ polymeric materials; they react to changes in pH, and so does chitosan. Our preliminary results show that polyacrylates are branched [1,2]. They also show that capillary electrophoresis [3] can separate them according to their branching structure [4], while it separates chitosan by its composition [5]. These polymers show promise for anticancer drug delivery. The different strategies to bind the drug to the polymer now need to be compared. The optimal strategy needs to be to a chemically simple process, to minimise the introduction of toxic moieties, to ensure that the bound drug will not leak when the loaded polymer is dissolved at pH 7.5. The loaded polymers will then be decorated with folic acid to ensure the accumulation of the drug carrier in cancerous tumours or poly(ethylene glycol) to prevent immune reactions. These binding reactions will be monitored, when possible online, using capillary electrophoresis methods. Aim of Study: To assess different synthetic pathways to bind anticancer drugs, such as cisplatin, and folic acid to the novel polyacrylates synthesized in Marseilles, as well as to chitosan. Methods: (In)organic synthesis. Capillary electrophoresis. Ethics Application Requirements: Not applicable Key References: [1] Gaborieau, P Castignolles, Size-exclusion chromatography (SEC) of branched polymers and polysaccharides. Analytical and Bioanalytical Chemistry 2011, 399, 1413-1423 [2] P Castignolles, R Graf, M Parkinson, M Wilhelm, M Gaborieau, Detection and quantification of branching in polyacrylates by size-exclusion chromatography (SEC) and melt-state 13C NMR spectroscopy. Polymer 2009, 50, 2373-2383. [3] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 [4] AR Maniego, D Ang, Y Guillaneuf, C Lefay, D Gigmes, JR Aldrich-Wright, M Gaborieau, P Castignolles, Separation of poly(acrylic acid) salts according to the topology using capillary electrophoresis in the critical conditions. Analytical and Bioanalytical Chemistry 2013, 405, 9009 [5] M Mnatsakanyan, JJ Thevarajah, RS Roi, A Lauto, M Gaborieau, P Castignolles, Separation of chitosan by degree of acetylation using simple free solution capillary electrophoresis. Analytical and Bioanalytical Chemistry 2013, 405, 6373-6378 34 Title of Project: Effect of temperature on branching in rice starch (FOR Code/s): Agriculture - Crop & Pasture Improvement (Selection and Breeding) (070305) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Rachelle Ward Email: [email protected] Co-supervisor: Dr Laura Pallas Email: [email protected] Location of Project: Parramatta Project Background The amount of amylose and the nature of its branching are influenced by night temperatures [1]. This degree of branching has been shown to directly impact the cooking quality and texture of the rice grain. The Waxy gene has been linked to changes in amylose although this does not explain all observed changes in amylose. One hypothesis to explain the amylose structure is the changed activity of starch branching enzymes, however these environmental influences, in combination with genetic differences in the waxy and starch branching enzyme genes have not been studied in the Australian rice germplasm. This investigation will analyse 12 parental lines of rice (Oryza sativa) from the rice breeding program at the Yanco Agricultural Institute. These lines comprise three variations of interest in the waxy gene, high amylose and low amylose contents (identifiable by 3 SNPs within the Waxy gene) along with two possible combinations of Starch Branching Enzymes. The 12 plants will be grown in replicates of 12 in a glasshouse until flowering where half will be moved to a higher temperature glasshouse and the other half to a control/normal temperature. Upon harvesting the amylose from the grain will be measured, then extracted by use of hot water and the starch structure will be analysed by capillary electrophoresis and NMR. Aim of Study: To measure degrees of branching using NMR spectroscopy [2], as well as amylopectin-to-amylose ratio and amylose chain lengths using capillary electrophoresis to identify the effect of night time temperatures on the activity starch branching enzyme. Methods: Capillary electrophoresis, NMR spectroscopy. Ethics Application Requirements: Not applicable Key References: [1] PA Counce, RJ Bryant, CJ Bergman, RC Bautista, YJ Wang, TJ Siebenmorgen, KAK Molenhauer, JFC Meullenet, Rice milling quality, grain dimensions, and starch branching as affected by high night temperatures. AACC International, 2005, 82(6), 645-648 [2] M Gaborieau, H DeBruyn, S Mange, P Castignolles, A Brockmeyer, RG Gilbert, Synthesis and characterization of synthetic polymer colloids colloidally stabilized by cationized starch oligomers. Journal of Polymer Science Part A Polymer Chemistry, 2009, 47, 1836-1852 35 Title of Project: New methods to characterise breakfast cereals (FOR Code/s): Analytical Chemistry – Separation Science (030108) Food Sciences - Food Chemistry and Molecular Gastronomy (excl. Wine) (090801) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Ashok Shrestha Email: [email protected] Telephone: 1296 Location of Project: Parramatta Project Background Breakfast cereals are nutrient-dense processed foods and are expected to have several health benefits. They are expected to have a low glycemic index (low GI, which means that they are digested slowly [1]). Most of them are also externally fortified with folic acid (Pteroylglutamic acid) to prevent the incidence of neural tube defects [2]. Their analysis is complicated by the fact that they are only partially soluble in water [3]. Traditional methods of folic acid analysis such as HPLC, or microbiological assay are tedious and time consuming. Our preliminary results showed that capillary electrophoresis is a fast method to detect folic acid. It is also an excellent tool of the separation and detection of sugars [4,5]. Aim of Study: The aim of the project is to develop new methods for a faster, more accurate, and robust characterisation of cereal-based foods, based on free-solution capillary electrophoresis. Folates and sugars will be quantified. These methods could be compared to the established, but tedious and expensive, HPLC methods. The full samples will also be characterised with solid-state NMR spectroscopy and ATR IR spectroscopy, thus avoiding dissolution artefacts. Methods: Capillary electrophoresis, NMR spectroscopy, ATR IR spectroscopy, high-performance liquid chromatography (HPLC). Ethics Application Requirements: Not applicable Key References: [1] AC Dona, G Pages, RG Gilbert, M Gaborieau, PW Kuchel, Kinetics of in vitro digestion of starches monitored by time-resolved 1H nuclear magnetic resonance. Biomacromolecules, 2009, 10, 638-644 [2] J Arcot, A Shrestha, Folate: methods of analysis. Trends in Food Science & Technology, 2005, 16, 253–266 [3] S Schmitz, AC Dona, P Castignolles, RG Gilbert, M Gaborieau, Assessment of the extent of starch dissolution in dimethylsulfoxide by 1H NMR spectroscopy. Macromolecular Bioscience 2009, 9, 506-514 [4] JD Oliver, M Gaborieau, EF Hilder, P Castignolles, Simple and robust determination of monosaccharides in plant fibers in complex mixtures by capillary electrophoresis and high performance liquid chromatography. Journal of Chromatography A, 2013, 1291, 179-186 [5] JD Oliver, AA Rosser, CM Fellows, Y Guillaneuf, JL Clement, M Gaborieau, P Castignolles, Understanding and improving direct UV detection of monosaccharides and disaccharides in free solution capillary electrophoresis. Analytica Chimica Acta 2014, 809, 183 36 Title of Project: Smart polymers as the additives of the future (FOR Code/s): Macromolecular and Materials Chemistry – Polymerisation mechanisms (030305) Analytical Chemistry - Separation Science (030108) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Prof Mathias Destarac Email: [email protected] Location of Project: Parramatta Project Background ’Smart’ polymeric materials react to changes in temperature or pH. These ‘smart’ polymers are intensively researched for use in drug delivery, water purification and more. The ‘smart’ behaviour of these materials is making their characterization difficult by common liquid chromatography methods. The team of Prof. Mathias Destarac (University Paul Sabatier, Toulouse, France) developed a new technology to synthesize some complex polymers in which part of the polymer chain is cationic, while the other part is neutral and thermoresponsive [1]. The cationic part ensures this polymer has great adhesive properties on a number of substrates. The thermoresponsive properties mean that the materials is water-soluble at low temperature but not at high temperature. Aim of Study: The characterization of these polymers has been extremely challenging up to now due to the presence of the charges. We propose to use this charge at our advantage and separate the polymers using an electric field, i.e. using capillary electrophoresis [2]. The self-assembly of these polymers leads to powerful and fascinating structures that could be characterized using solid-state NMR [3]. Methods: Capillary electrophoresis, solid-state NMR spectroscopy. Ethics Application Requirements: Not applicable Key References: [1] M Destarac, On the critical role of RAFT agent design in reversible addition-fragmentation chain transfer (RAFT) polymerization. Polymer Reviews 2011, 51, 163-187 [2] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 [3] W Gu, M Gaborieau, VT Huynh, PL de Souza, MH Stenzel, Functionalization of microspheres with malonates using Michael addition as a pathway to create a drug delivery system for platinum drugs for the treatment of liver cancer. Polymer 2011, 52, 5993-6002 37 Title of Project: Structure of polyamides and adhesive properties (FOR Code/s): Macromolecular and Materials Chemistry – Chemical characterisation of Materials (030301) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Richard Wuhrer Email: [email protected] Telephone: 9089 Location of Project: Parramatta Project Background Polyamides have been a very successful industrial story since their discovery in the 1930s by the company Dupont de Nemours. Nylon is likely the most well-known member of this family. The difficulties to characterise these polymers may have limited the expansion of this family. One key innovation has however been the use of fatty acids (from paper production for example) to produce polyamides for industrial adhesives (hot-melt adhesives). These polyamides come from a sustainable and renewable source, but they are then complex in terms of chemical structure, namely composition. We have shown that capillary electrophoresis (CE) is a simple and robust method to characterise the composition of complex polysaccharides.[1,2] This method will be applied to polyamide subjected to acid hydrolysis. The resulting samples will also be analysed with solution-state NMR spectroscopy. The hydrolysis should only lead to depolymerisation but other degradation processes may also take place. Adhesives, as most industrial materials, are loaded with a number of additives. To investigate potential degradation and the presence of additives, solid state characterisation methods will also be applied: solid-state NMR [3] and ATR IR spectroscopies. This project can lead to collaborations and job opportunities in various manufacturing companies. Aim of Study: To relate the chemical composition of hot meld adhesives to their adhesive properties. Methods: Capillary electrophoresis, solution-state and solid state NMR spectroscopies, ATR IR spectroscopy Ethics Application Requirements: Not applicable Key References: [1] JD Oliver, M Gaborieau, EF Hilder, P Castignolles, Simple and robust determination of monosaccharides in plant fibers in complex mixtures by capillary electrophoresis and high performance liquid chromatography. Journal of Chromatography A 2013, 1291, 179-186 [2] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 [3] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386 38 Title of Project: What is a true solution (of chitosan)? Does it exist? And why does it matter? (FOR Code/s): Macromolecular and Materials Chemistry - Physical Chemistry of Materials (030304) Analytical Chemistry - Separation Science (030108) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Michael O’Connor Email: m.o'[email protected] Telephone: 3902 Location of Project: Mainly Parramatta, but also Campbelltown for cell culture Project Background Chitosan is an amazing polymer derived from chitin, the main component of crab or prawn shells and many others. On top of being a renewable and sustainable material, chitosan is bacteriostatic and it has thus a great potential to produce films for cell culture or transplantation and regenerative medicine.[1] Our research group has developed a methodology to functionalise chitosan films with small biomolecules and quantify the grafting and these biomolecules.[2] However, the homogeneity of the film surface currently needs to be improved. The films are obtained by casting a chitosan “solution” and evaporating the solvent. Preliminary investigations show that the heterogeneity of the chitosan film surface may arise from the presence of aggregates in the chitosan “solution”. Pressure mobilisation or capillary electrophoresis can give a quick assessment of the kinetics of dissolution of the chitosan available from different sources. This can be completed by time-resolved NMR spectroscopy [3] and then quantitative NMR spectroscopy [4]. Different methods to cast the films will also be investigated and compared. Cells will be cultured on these films to assess the homogeneity of the film surface as well as the film-to-film variability. By identifying ways of improving chitosan film production, this project will advance the fields of both polymer chemistry and regenerative medicine. Aim of Study: To obtain a true chitosan solution for reproducible casting of chitosan film with homogenous surfaces Methods: Capillary electrophoresis, NMR spectroscopy, Cell culture Ethics Application Requirements: Not applicable Key References: [1] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis and X-ray diffraction. Biomacromolecules 2011, 12, 1380 [2] C Lefay, Y Guillaneuf, G Moreira, JJ Thevarajah, P Castignolles, F Ziarelli, E Bloch, M Major, L Charles, M Gaborieau, D Bertin, D Gigmes, Heterogeneous modification of chitosan via nitroxide-mediated polymerization. Polymer Chemistry 2013, 4, 322 [3] A Dona, C-WW Yuen, J Peate, RG Gilbert, P Castignolles, M Gaborieau, A new NMR method for directly monitoring and quantifying the dissolution kinetics of starch in DMSO. Carbohydrate Research 2007, 342, 2604 [4] S Schmitz, AC Dona, P Castignolles, RG Gilbert, M Gaborieau, Assessment of the Extent of Starch Dissolution in Dimethyl Sulfoxide by 1H NMR Spectroscopy. Macromolecular Bioscience 2009, 9, 506. 39 Title of Project: Importance of branching and debranching in anticancer drug carriers (FOR Code/s): Biological Sciences, Analytical Biochemistry (060101) Macromolecular and Materials Chemistry - Synthesis of Materials (030306) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Prof. Jens Coorssen Email: [email protected] Telephone: 3802 Location of Project: Parramatta Project Background Poly(acrylic acid) is used in our research group to produce potential anticancer drug carriers. This polymer is smart: it reacts to pH changes thus releasing the drug in acidic media such as tumours. Large molecule such as polymers can either have a linear structure or a branched one (tree-like). We have shown that poly(acrylic acid) is branched [1] and this is beneficial to ensure that the drug does not leak out of the polymer in physiological conditions. The branched structure controls the release and retention of the drug. To understand these, the size (molar mass distribution) of the branches needs to be determined. In addition, the poly(acrylic acid) drug carrier is too large to be eliminated by the body after the drug delivery. Poly(acrylic acid) was designed to be debranched into small fragments on a longer time frame. The kinetics of debranching in physiological conditions will be investigated to ensure that the drug carrier does not accumulate for example in the kidneys. Aim of Study: To debranch a branched poly(acrylic acid) to characterise the branches and assess the potential of this poly(acrylic acid) for anticancer drug delivery. Methods: Capillary Electrophoresis, NMR spectroscopy Ethics Application Requirements: Not applicable Key References: [1] A Maniego, D Ang, Y Guillaneuf, C Lefay, D Gigmes, J Aldrich-Wright, M Gaborieau, P Castignolles, Separation of poly(acrylic acid) salts according to topology using capillary electrophoresis in the critical conditions. Analytical and Bioanalytical Chemistry 2013, 405, 9009 40 Field of Research: Title of Project: 0204 0301 0303 0306 Investigation of diffusive averaging and viscosity effects in bimodal polymer solutions Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Assoc. Prof. Gary Dennis [email protected] 9685 9939 Dr Scott A Willis [email protected] 4620 3114 Campus project is offered and conducted: Campbelltown Background (max 500 words) The most fundamental form of molecular transport is self-diffusion – the random motion of molecules – and measurements of which provide information on the size of the molecule as well as any influences from restrictions/obstructions (e.g., diffusion in a cell or porous rock) or aggregation processes (e.g., drug-binding). A powerful, versatile and non-invasive method for measuring self-diffusion is pulse gradient spin-echo (PGSE) nuclear magnetic resonance (NMR). However, measurements of self-diffusion in polydisperse systems (e.g., polymer solutions with different molecular weight polymers present or aggregating proteins) is complicated by diffusive averaging effects since the NMR signals are the same or overlapped. Studying diffusive averaging in bimodal polymer solutions is of great significance as synthetic (e.g., polystyrene) and natural (e.g., proteins) polymers are inherently polydisperse. In this project, diffusive averaging will be studied for different bimodal polymer solutions (i.e., two molecular weights or two types of polymers present) of either chemically identical polymers of different molecular weights or mixtures of chemically different polymers of different or similar molecular weights. Several types of polymers could be considered for this study. Measurements of the viscosity of bimodal and monomodal polymer solutions will help to elucidate the diffusive averaging processes. (Would suit students interested in Physical chemistry/Mathematics/NMR) Aim of Study: To use NMR diffusion measurements and viscosity measurements to develop better models for diffusive averaging phenomena. Methods: Viscometry and NMR diffusometry. Ethics Application Requirements: Not Applicable Key References: 5. Price, W. S., NMR Studies of Translational Motion. Cambridge University Press: New York, 2009. 6. Willis, S. A.; Dennis, G. R.; Zheng, G.; Price, W. S. Macromolecules 2010, 43, 7351-7356. 7. Willis, S. A.; Price, W. S.; Eriksson-Scott, I. K.; Zheng, G.; Dennis, G. R. J. Mol. Liq. 2012, 167, 110-114. 8. Callaghan, P. T.; Pinder, D. N. Macromolecules 1985, 18, 373-379. 41 Title of Project: Using stem cell-derived lens epithelial cells to study primary and secondary cataract. (FOR Code/s): 0601, 1103, 0303, 0301 Supervisor: Dr Michael O’Connor Contact: [email protected] Location of Project: School of Medicine, Campbelltown Campus Project Background: Primary and secondary cataracts in adults, children and babies place a large burden on medical health systems worldwide. Ocular lens surgery is currently the only option to restore vision in these patients, but costs billions of dollars annually around the world. It is therefore clear that anti-cataract drug screening methods need to be developed in order to identify compounds that can inhibit or delay the formation or progression of primary and secondary cataract. Until now, development of such methods has been severely hampered by limited access to normal human lens tissue. Encouragingly, my group recently established a new method for generating pure populations of human lens epithelial cells from pluripotent stem cells. This new source of human lens cells will enable the establishment of methods for high-throughput anti-cataract drug screening. It may also enable regeneration of functional human lenses in vitro, similar to the in vitro regenerated rat lenses previously generated by my group. Such in vitro human lenses could be used for studies of lens and cataract development, toxicology studies of new drugs and cosmetics, and identification of anti-primary cataract drugs. Aim of Study: This study will give students training in key stem cell and regenerative medicine techniques specific to lens and cataract research that are also highly relevant to regenerative medicine approaches to all human tissues. Students will be encouraged to present their work at conferences and publish their findings in peer reviewed journals Methods: Students will be taught widely applicable regenerative medicine techniques including tissue culture maintenance of human pluripotent stem cells, directed differentiation to ocular lens cells, purification of lens epithelial cells, production of lens fibre cells for in vitro human lens regeneration, and application of lens epithelial cells to drug screening. Cell type characterisation will be performed by a range of techniques including flow cytometry, polymerase chain reaction, and high-content imaging. Students considering this project must be comfortable working with human embryonic stem cells before applying. Ethics Application Requirements: Appropriate ethics and biosafety approvals have been obtained for the project. Key References: 1. O’Connor and McAvoy. In vitro generation of functional lens-like structures with relevance to age-related nuclar cataract. Investigative Ophthalmology and Visual Science. 2007. 48(3):1245-52. 2. Yang et al. Efficient generation of lens progenitor cells and lentoid bodies from human embryonic stem cells in chemically defined conditions. FASEB J. 2010. 24(9):3274-83. 3. Murphy and O’Connor. A rapid, simple and efficient method for generating pure populations of lens epithelial cells from human pluripotent stem cells. In preparation. 42 Inorganic Chemistry 43 Title of Project: Role of tachykinin neuropeptides in the regulation of synaptic copper homeostasis. (FOR Code/s): 030201 (50%), 060105 (35%), 060112 (15%) Supervisor: Dr Christopher Jones Contact: [email protected], ph: 9685 9908 Co-supervisor: Dr Mark Jones Contact: [email protected] Location of Project: Parramatta Project Background Tachykinin neuropeptides are involved in diverse biological functions, including regulating neuroprotective and neuroinflammatory pathways in the brain. In a neuroprotective capacity, these peptides have been shown to protect against neurotoxic processes in Alzheimer’s disease, yet it is not clear how they achieve this. One feature of Alzheimer’s disease is the disruption of normal copper homeostasis in the brain. Normally, neurons can release the metal into the synapse where it is thought to modulate the activity of proteins, such as receptors, that function within the synapse. There is now evidence that some tachykinin neuropeptides are able to bind copper, and recent work from our laboratory has shown that one member, neurokinin B, can inhibit the uncontrolled cellular uptake of the metal into brain cells called astrocytes. Uncontrolled cellular copper uptake results in disruption to intracellular calcium levels, and also promotes formation of dangerous reactive oxygen species, and both processes contribute to cell death. We hypothesis that neurokinin B is a key member of synaptic copper homeostasis, which helps protect brain cells against copper-induced toxicity, and that loss of this activity contributes to cell death observed in Alzheimer’s disease. This project would suit someone with an interest in cell biology and biochemistry. Aim of Study: This study will investigate how neurokinin B, and two other tachykinins, neur influence and control copper uptake into both neurons and astrocytes. Key questions to answer are: 1. Do the tachkinins completely inhibit copper uptake, or do they just ensure metal uptake occurs only via correct pathways? 2. Is the effect on astrocytes the same as neurons, or is the ability to control copper uptake cell specific? 3. Does copper remain bound to the tachykinins even in the presence of specific tachykinin receptors? 4. Does copper-bound NKB influence trafficking of the NKB-receptor to the nucleus? Methods: Cell culture of neurons and astrocytes, fluorescence spectroscopy, confocal microscopy, western blotting. Ethics Application Requirements: None required. Key References: Russino DR, McDonald E, Hejazi L, Hanson GR, Jones CE. The tachykinin neuropeptide Neurokinin B binds copper forming an unusual [Cu(II)(NKB)2] complex, and inhibits copper uptake into 1321N1 astrocytes. ACS Chem. Neurosci. 4(10), 1371-81, 2013. Grosas AB, Kalimuthu P, Smith AC, Williams PA, Millar TJ, Bernhardt PV and Jones CE. The tachykinin peptide neurokinin B binds Cu(I) and Ag(I) and undergoes quasi-reversible electrochemistry. Towards a new role for the peptide in the brain. Neurochem. Int. 70, 1-9, 2014 44 Title of Project: Elucidating the structure and metal-binding properties of peptides that regulate feeding in starfish. (FOR Code/s): 030201 (30%), 060105 (35%), 060112 (35%) Supervisor: Dr Christopher Jones Contact: [email protected], ph: 9685 9908 Co-supervisor: Dr Feng Li Contact: [email protected], ph 9685 9987 Location of Project: Parramatta Project Background The SALMFamides are a family of neuropeptides found in species of the phylum Echinodermata (e.g. starfish) where they appear to function as muscle relaxants. Starfish feed by everting their stomach over their prey and, as muscle relaxants, the SALMFamides help trigger stomach eversion. We have characterised two neuropeptides, called S1 and S2 where S1 is an octapeptide (GFNSALMF-NH2) and S2 is a dodecapeptide (SGPYSFNSGLTF-NH2). S2 is 10 times more potent than S1, and potency is a combination of both primary sequence and the structure adopted by the neuropeptide. Intriguingly, S2 is able to self-associate and is so far unique in this ability within the SALMFamide family. However, these peptides are cleaved from precursor proteins that contain at least seven other SALMFamides, and all are presumably functionally present at the same time. We don’t know if these other peptides can either self-associate or interact with each other to form dimers or larger structures. Based on sequence analysis of some SALMFamides, we predict that metals may help regulate association by acting as a link between different peptides. Understanding the mechanisms underlying starfish feeding may open new avenues for controlling crown-of-thorn feeding on corals of the Great Barrier Reef. This project would suit someone with an interest in protein structure and coordination chemistry. Aim of Study: This study will investigate the structure and metal-binding behaviour of six SALMFamide neuropeptides from Asterias rubens. Key aims to answer are: 5. Do any peptides undergo self-assocation to form dimers or higher order structures? 6. What conditions promote self-association? 7. Do any of the peptides bind metals – specifically copper, zinc or nickel, and what is the affinity for the different metal ions? 8. How do metal ions influence peptide structure – e.g. can metal-linked dimers or oligomers of different peptides be formed? Methods: Electronic spectroscopy, Nuclear magnetic resonance, Circular dichroism. Ethics Application Requirements: N/A. Key References: Otara C, Jones CE, Younan ND, Viles JH and Elphick MR. Structural analysis of the starfish SALMFamide neuropeptides S1 and S2: The N-terminal region of S2 facilitates self-association. BBA-Proteins and Proteomics. 1844, 358-265, 2014. Jones CE, Otara C, Younan ND, Viles JH and Elphick MR. Bioactivity and structural properties of chimeric analogs of the starfish SALMF-amide neuropeptides S1 and S2. BBA-Proteins and Proteomics, 1844, 1842-1850, 2014. 45 Title of Project: Developing new anticancer drugs using flow chemistry (FOR Code/s): 030201 Bioinorganic Chemistry & 030401 Biologically Active Molecules Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Christopher Gordon Contact: [email protected] Location of Project: Campbelltown Project Background: This project aims to advance a branch of chemistry known as flow-chemistry. This emerging technology has the potential to revolutionize pharmaceutical production by improving quality and reducing chemical waste. However, if flow chemistry is to be embraced by the broader synthetic community a number of significant limitations need to be addressed. Thus the aim of this project is to address a number of these limitations by devising cutting-edge total-flow-synthesis methods by produce a series of platinum(II) compounds which possess exceptional anticancer activity. Aim of Study: To develop a procedure to synthesise and characterise platinum(II) complexes using flow chemistry. Methods: Uses both conventional inorganic and flow chemistry for synthesis, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel platinum(IV) complexes will be synthesised using both conventional and Flow chemistry and characterised using a combination of 1H and 195Pt nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional 1H / 195Pt heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). The biological activity of the synthesised complexes will be undertaken with the assessment of cellular cytotoxicity and interactions with DNA. Ethics Application Requirements: None required Key References: 1. Metal Complexes and Therapeutic uses thereof, Fenton, R.R. and Aldrich-Wright, J.R. International Patent, Application Number PCT/AU02/00167, Oct., 2002 2. Fisher, D. M.; Bedarski, P. J.; Grunert, R.; Turner, P.; Fenton, R. R.; Aldrich-Wright, J. R. Chiral platinum(II) metallointercalators with potent in vitro cytotoxicity activity, ChemMedChem (2007), 2, 488-495. 3. Brodie, C.; Collins, J.G.; Aldrich-Wright, J.R. The biological activity of some square-planar platinum(II) metallointercalators. Journal of the Chemical Society, Dalton Transactions (2004), 1145-1152. 4. Krause-Heuer, A. M.; Grünert, Kühne, R. S.; Buczkowska, M.; Wheate, N. J.; Le Pevelen, D.; Boag, L. R.; Fisher, D. M.; Kasparkova, J.; Malina, J.; Bednarski, P. J. Brabec, Patrick V.; Aldrich-Wright, J. R. (2009) Studies into the mechanism of action of platinum(II) complexes with potent cytotoxicity in human cancer cells. Journal of Medicinal Chemistry, 52, 5474-5484. 5. Talib, J.; Beck, J. L.; Urathamakul, T.; Nguyen, C. D.; Aldrich-Wright, J. R.; Mackay, J. P.; Ralph, S. F. (2009) A mass spectrometric investigation of the ability of metal complexes to modulate transcription factor activity. Chemical Communications, (37), 5546-5548. 6. Fisher, D. M.; Fenton, R. R.; Aldrich-Wright, J.R. In vivo studies of a platinum(II) metallointercalator. Chemical Communications, (2008), 43, 5613-5615. 7. Krause-Heuer, A. M.; Grant, M. P.; Orkey, N.; Aldrich-Wright, J. R. Drug delivery devices and targeting agents for platinum(II) anticancer complexes, Australian Journal of Chemistry. Invited paper (2008), 61, 675-681. 8. Al Otaibi, A., Gordon, C. P., Sakoff, J. A., and McCluskey, A., The influence of ionic liquids on the Knoevenagel condensation of 1H-pyrrole-2-carbaldehyde with phenyl acetonitriles – cytotoxic 3-substituted-(1H-pyrrol-2yl)acrylonitriles, RSC Adv., 2014, 4, 19806 – 19813. 9. Hizartzidis, L., Tarleton, M., Gordon, C. P, McCluskey, A. Chemoselective Flow Hydrogenation Approaches to Isoindole-7-carboxylic acids and 7-Oxa-Bicyclio[2.2.1]heptanes, RSC Adv., 2014, 4, 9709-9722. 10.Gordon, C. P.; Hizartzidis, L.; Tarleton, M.; Sakoff, J. A.; Gilbert, J.; Campbell, B. E.; Gasser, R. B.; McCluskey, A. Discovery of acrylonitrile-based small molecules active against Haemonchus contortus. MedChemComm 2014, 5, 159-164.Tarleton, M.; Young, K. A.; Unicomb, E.; McCluskey, S. N.; Robertson, M. J.; Gordon, C. P.; McCluskey, A. A flow chemistry approach to norcantharidin analogues. Lett. Drug Des. Discovery 2011, 8, 568-574. 46 Title of Project: Synthesis of agents to prevent the formation of biofilms (FOR Code/s): 030201 Bioinorganic Chemistry & 030401 Biologically Active Molecules Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Ming Wu Contact: [email protected] Co-supervisor: Christopher Gordon Contact: [email protected] Location of Project: Project Background: As bacterial infection rate soar and death toll climbs, there is an urgent need to develop new reliable antibacterial drugs that are effective against bacterial infection and biofilms, a community of bacteria with extraordinary resistance to almost every drug developed to date. This project builds upon previously results, where the antimicrobial potential of some copper(II) complexes of the general structure [Cu(L1)(L2)]2+ (where L1 is a substituted 1,10-phenanthroline ligand and L2 is a diamine ligand, examples left) against Staphyloccocus aureus proved to be particularly promising (shown below).1 Positive control Vancomycin Cu-56MESS CLSM images of biofilms that were untreated (left panel), treated for 2 hours with vancomycin at 100 g/mL (centre panel) or Cu-56MESS at 100 g/mL (right panel). Side views of the biofilms are shown on top and on the right of each panel.6 Aim of Study: To synthesise and characterise complexes with antibacterial activity and of particular interest is biofilm eradication. Methods: Uses molecular modelling for design, both conventional inorganic and flow chemistry for synthesis, UV and CD for characterisation and biophysical techniques for biological assessment. The complexes will be synthesised and characterised using a combination of UV, CD, elemental analysis and electrospray ionisation mass spectroscopy (ESIMS). The biological activity of the synthesised complexes will be undertaken with the assessment of antibacterial activity and determination of the impact on biofilms. Ethics Application Requirements: None Key References: 1. N. S. Ng, MSc Thesis, University of Western Sydney, 2012. 2. J. M. Andrews, J. Antimicrob. Chemother., 2001, 48, 5. 3. Krause-Heuer, A.M., Leverett, P., Bolhuis, A., and Aldrich-Wright, J.R. (2012). Aust J Chem 65, 860-873. 4. Ng, N.S., Leverett, P., Hibbs, D.E., Yang, Q., Bulanadi, J.C., Wu, M.J., and Aldrich-Wright, J.R. (2013). Dalton Transactions 42, 3196-3209. 5. Beeton, M.L. Aldrich-Wright, J.R. and Bolhus, A. Anti-biofilm activity of copper(II) complexes, Journal of Inorganic Biochemistry 140 (2014) 167–172 47 Title of Project: Designing and synthesising compounds that selectively bind to quadruplex DNA (FOR Code/s): 030201 Bioinorganic Chemistry & 030401 Biologically Active Molecules Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Steven Ralph Contact: [email protected] Co-supervisor: David Harman Contact: [email protected] Co-supervisor: Christopher Gordon Contact: [email protected] Location of Project: Campbelltown Project Background: The recent discovery that non-classical Gquadruplex DNA (QDNA) structures exist in vivo has opened a new avenue for anticancer research. The unique structural features of QDNA provide a novel target for chemotherapeutic drug design and synthesis of QDNA selective small molecules is a flourishing area of research. This project intended to contribute to the design of novel anticancer agents through the further development of terpyridineplatinum(II) complexes (where terpyridine = 2,2':6',2''-terpyridine, terpy) which have demonstrated QDNA binding affinity. Aim of Study: : A series of novel platinum compounds will be synthesised that interact with Q-DNA. Methods: Uses molecular modelling for design, both conventional inorganic and flow chemistry for synthesis, preparative HPLC, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, twodimensional 1H correlation spectroscopy (NOSY), 2D heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). Ethics Application Requirements: None required Key References: 1. Harper, B. W. J.; van Holst, M.; Aldrich-Wright, J. R. (2011) Platinum(II) Intercalating Complexes Based on 2,2':6',2''Terpyridine. In: Metallointercalators, Synthesis and Techniques to Probe Their Interactions with Biomolecules (J. Aldrich-Wright, Ed.), Springer. 1st Edition. 2. Garbutcheon-Singh, K.B.; Grant, M.P.; Harper, B.W.; Krause-Heuer, A. M.; Manohar, M.; Orkey, N. U.; Aldrich Wright, J. R. (2011) Transition Metal Based Anticancer Drugs. Current Topics in Medicinal Chemistry, Invited paper. 11(5), 521-542. 3. Harper B. W.; Krause-Heuer, A. M.; Grant, M.P.; Manohar, M.; Garbutcheon-Singh,K. B.; Aldrich-Wright, J. R. (2010) Advances in platinum chemotherapeutics. Chemistry-A European Journal, 16, 7064-7077. 48 Title of Project: Development of diagnostic radiopharmaceuticals (FOR Code/s): 030201 Bioinorganic Chemistry & 030401 Biologically Active Molecules Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Christopher Gordon Contact: [email protected] Co-supervisor: Ivan Greguric Contact: [email protected] Co-supervisor: Ben Fraser Contact: [email protected] Location of Project: Campbelltown/ANSTO Project Background: [18F]fluorodeoxyglucose or FDG – the world’s most commonly prescribed fluorine-18 radiopharmaceutical is used to diagnose many forms of cancer through positron emission tomography (PET) imaging (see LHS image). FDG is preferentially taken up in cancer cells and is utilised for initial cancer diagnosis and for monitoring treatment progression. Although numerous radioisotopes are available for Positron Emission Tomography (PET) medical imaging, fluorine-18 remains very popular due to favourable physical properties. These include low energy positron emission (0.202 MeV), excellent decay profile (97% β+ emission), advantageous half-life (110 mins) and similar steric and electronic properties to the hydroxyl group. Currently we are developing fluorine-18 radiopharmaceuticals as diagnostic imaging agents for Alzheimer’s disease (metal chelators) and depression (organic cation 3 transporter inhibitors). Student top-up scholarships – The Australian Institute of Nuclear Scientists and Engineers (ANISE): UWS students undertaking honours projects in collaboration with ANSTO are eligible to apply for an honours scholarship ($5000 stipend) from AINSE. http://www.ainse.edu.au/grad_students2/honours_scholarships Aim of Study: To synthesise and characterise [18F]Diagnostics PET imaging agents for Alzheimers’s disease or depression. Methods: Uses molecular modelling for design, radiochemistry and flow chemistry for synthesis, preparative HPLC, radio HPLC, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, twodimensional 1H correlation spectroscopy (NOSY), two-dimensional heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). Ethics Application Requirements: None required Key References: 1. Brookmeyer, R. (1998) American Journal of Public Health 88, 7 2. Ferri, C. P., Prince, M., et.al.(2005) Lancet 366, 2112-2117 3. Bush, A. I., and Tanzi, R. E. (2008) Neurotherapeutics 5, 421-432 4. Bush, A. I. (2008) Journal of Alzheimer's Disease 15, 223-240 5. Sacco, C., Skowronsky, R. A., Gade, S., Kenney, J. M., and Spuches, A. M. (2012) JBIC, J. Biol. Inorg. Chem. 17, 531541 6. Sanghamitra, N. J. M., Varghese, N., and Rao, C. N. R. (2010) Chem. Phys. Lett. 496, 104-108 7. Miller, P. W., Long, N. J., Vilar, R., and Gee, A. D. (2008) Angewandte Chemie International Edition 47, 8998-9033 8. Toyama, H. (1993) Radioisotopes 42, 365-376 9. Vasdev, N., Cao, P., van Oosten, E. M., et.al. (2012) MedChemComm 3, 1228-1230 10. Babudri, F., Cardone, A., Cioffi, C. T., Farinola, G. M., Naso, F., and Ragni, R. (2006) Synthesis 2006, 1325-1332 11. Helin, A. F., and Vanderwerf, C. A. (1952) The Journal of Organic Chemistry 17, 229-232 12. Adlard, P. A., Cherny, R. A., et.al and Bush, A. I. (2008) Neuron 59, 43-55 13. Barnham, K. J., Kenche, V. B., et.al. (2008) Proceedings of the National Academy of Sciences 105, 6813-6818 14. Engel, Y., Dahan, A., Rozenshine-Kemelmakher, E., and Gozin, M. (2007) The Journal of Organic Chemistry 72, 2318-2328 15. Ross, T. L., Ermert, J., Hocke, C., and Coenen, H. H. (2007) Journal of the American Chemical Society 129, 80188025 16. Cai, L., Lu, S., and Pike, V. W. (2008) European Journal of Organic Chemistry 2008, 2853-2873 17. Olah, G. A., Chambers, R. D., and Prakash, G. K. S. (1992) Synthetic Fluorine Chemistry, John Wiley & Sons Inc 18. Wester, H. J. (2010) Pharmaceutical Radiochemistry (I), Scintomics, Furstenfeldbruck 49 Title of Project: Developing New Radio-metal PET Tracers: Ligands for Oxophillic Radio-metals (FOR Code/s): Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Ivan Greguric Contact: [email protected] Co-supervisor: Nigel Lengkeek Contact: [email protected] Co-supervisor: Ben Fraser Contact: [email protected] Campus/s project is offered and conducted: ANSTO Project Background: Zirconium-89 (89Zr) is a positron emitting radionuclide well suited to Positron Emission Tomography (PET) molecular imaging studies. Its long physical half-life, 78.4 hrs, makes it uniquely suited to imaging with molecules that have long biological half-lives and localisation times, the key example being monoclonal antibodies, so called 89Zr-Immuno-PET. There has been tremendous growth in the area of ‘biologicals’ for treatment of human disease, particularly cancer. The bacterial iron siderophore, desferrioxamine B (DFO), a trishydroxamate ligand is the most promising ligand for 89Zr and it is easily incorporated onto biomolecules (shown left). Radiolabelling of DFOfunctionalised antibodies with 89Zr is rapid and efficient with the radiolabelled biomolecules being largely stable in-vivo. However, there are a growing number of cases that show significant bone uptake. This is undesirable as it can lead to radiation to the sensitive bone marrow. To combat this problem we are developing a series of tetrahydroxamate ligands (an example is shown below) to tie up the two remaining coordination sites of Zr where other ligands can displace the DFO. This will hopefully improve their in-vivo stability. The ligands will be suitable for a range of emerging PET radioisotopes including 45Ti (t1/2 = 3.08 hr), 44Sc (t1/2 = 3.93 hr), 90Nb (t1/2 = 14.6 hr) and 89Zr (t1/2 = 78.4 hr). Student top-up scholarships – The Australian Institute of Nuclear Scientists and Engineers (ANISE): UWS students undertaking honours projects in collaboration with ANSTO are eligible to apply for an honours scholarship ($5000 stipend) from AINSE. http://www.ainse.edu.au/grad_students2/honours_scholarships Aim of Study: To synthesise and characterise tetrahydroxamate ligands for Zr89 complexation and antibody radiolabelling. Methods: Uses inorganic and synthetic chemistry for preparation of new ligands and ‘cold’ metal complexes; radiochemistry for the optimisation of radiolabelling procedures and biological labelling; Prep-HPLC, radio-HPLC, radio-TLC, NMR, UV-Vis, ESI-MS, LC-MS-MS, pH auto-titrations for characterisation; molecular modelling for design of ligands and biophysical techniques for the assessment of radiolabelled biological molecules. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, 2D 1H correlation spectroscopy (NOSY), two-dimensional heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). Ethics Application Requirements: None required Key References: 1. Bergeron, R.J.,. Chem. Rev., 1984. 84: p. 587 - 602. 2. Butler, A. and R.M. Theisen, Coord. Chem. Rev., 2010. 254: p. 288 - 296. 3. Hider, R.C. and X. Kong, Nat. Prod. Rep., 2010. 27: p. 637 - 657. 4. Raymond, K.N., G. Muller, and B.F. Matzanke, Top. Curr. Chem., 1984. 123: p. 50 - 101. 5. Deri, M.A., et al., Nuclear Medicine and Biology, 2013. 40(1): p. 3-14. 6. Zalutsky, M.R., Clinical Cancer Research, 2006. 12(7): p. 1958-1960. 7. Vugts, D.J. and G.A.M.S. van Dongen, Drug Discovery Today: Technologies, 2011. 8(2–4): p. e53-e61. 8. Wright, B.D. and S.E. Lapi, Journal of Nuclear Medicine, 2013. 54(8): p. 1171-1174. 50 Title of Project: The assembly of halogen bonding helicates in solution. (FOR Code/s): 030302 Nanochemistry and Supramolecular Chemistry & 030205 Non-metal Chemistry Supervisor: Nathan Kilah Contact: [email protected] (UWS address TBA) Location of Project: Parramatta (a) (b) Project Background: Supramolecular chemistry is the study of large Me N molecular assemblies held together by a number of weak, yet highly N N Me specific interactions, and can be considered as a “bottom-up” approach to Me N N N X n n nanotechnology. Supramolecular synthetic targets are often designed for X X A X specific topology, symmetry, shape, or function or with the focus on mimicking the complex self-assembled molecules present within X N N n N nN biological systems. One specific example to be investigated in this project Me N is the mimicry of self-assembled helicates (such as nucleic acids and αhelices of proteins) in solution. This will be investigated through the use of 2D representation of a 3D halogen bonds, an underexplored class of non-covalent interaction. halogen bonding helicate. Halogen bonds are attractive interactions formed between positively polarised halogen atoms (specifically bromine and iodine) and electron rich Lewis bases. These interactions, though similar in strength to hydrogen bonds, are highly directionally dependent, and previous investigations have focused on crystal engineering and liquid crystal applications. This project will examine the application of halogen bonding to the assembly of helicates in solution and in the solid state. Solution phase studies will examine the structure, stability and fluxional properties of these helicates, and will investigate the influence of chiral anions on the helical twist of the halogen bonding structures. Aim of Study: The synthesis of halogen bonding helicates, investigating their properties in solution, and influencing their three dimensional structure through the use of chiral anions. Further areas of investigation included the use of anions as templating agents, and the preparation of larger scale, polymeric structures. Methods: Molecular modelling for helicate design. Modern organic synthesis, including the use of transition metal catalysts, characterisation of new compounds by NMR, MS, elemental analysis, X-ray crystallography and Circular Dichroism experiments. Solution phase characterisation will use NMR technique to examine the size of dissolved molecular assemblies, and the influence of chiral anions on the helicity. Ethics Application Requirements: None required. Key References: 1. Kilah, N. L.; Wise, M. D.; Serpell, C. J.; Thompson, A. L.; White, N. G.; Christensen, K. E.; Beer, P. D. J. Am. Chem. Soc. 2010, 132, 11893–11895. 2. Kilah, N. L.; Wise, M. D.; Beer, P. D. Cryst. Growth Des. 2011, 11, 4565–4571. 3. Farina, A.; Meille, S. V.; Messina, M. T.; Metrangolo, P.; Resnati, G.; Vecchio, G. Angew. Chem. Int. Ed. 1999, 38, 2433–2436. 4. Erdelyl, M. Chem. Soc. Rev. 2012, 41, 3547–3557. 51 Title of Project: Enantiomeric separation of pharmaceuticals by halogen bonding or coordination chemistry. (FOR Code/s): 030207 Transition Metal Chemistry or 030205 Non-metal Chemistry Supervisor: Nathan Kilah Contact: [email protected] (UWS address TBA) Location of Project: Parramatta Project Background: Stereochemistry is concerned with the study of the three-dimensional arrangements of atoms and molecules in space. One major area of interest in this field is the separation of mirror image chemical compounds, known as enantiomers. These enantiomers have identical properties to one another, but have dramatically different interactions with other molecules possessing stereochemistry (e.g. a drug with a protein target). The separation of these enantiomers is essential for many compounds, most notably pharmaceuticals, where the mirror enantiomer may be toxic or otherwise harmful. The separation of one enantiomer as solid crystals from a mixture of the enantiomers is fundamentally a crystal engineering problem. Two thematically related projects are available in this area, each focusing on a unique method for the separation of enantiomers of pharmaceuticals. Halogen bonding has been studied extensively in crystal engineering, but there is no literature precedence for the use of halogen bonds in the separation of enantiomers from solution (called a resolution). Pioneering the resolution of chiral compounds through the application of halogen bonding will add to the toolkit of stereochemists for the separation of target enantiomers from complex mixtures. Pharmaceutically relevant separations will be attempted as proof of application (e.g. ibuprofen, zopiclone, modafinil, cetirizine). Enantiomeric resolution through the application of coordination chemistry is also available as a separate avenue of research. Enantiomerically pure platinum(II) complexes derived from the chiral diphosphine ligands BINAP will be used to separate a number of pharmaceuticals derived from glycerol (e.g. guaifenesium, dropopizine). Further explorations in the metal-based asymmetric synthesis of enantiomerically pure pharmaceuticals are an additional area of investigation. Aim of Study: Separation of pharmaceutical enantiomers by resolution with either halogen bonding reagents, or platinum(II) complexes. Methods: Modern organic and inorganic synthesis including the use of transition metal catalysts, characterisation of new compounds by NMR, MS, elemental analysis, X-ray crystallography and Circular Dichroism experiments. Resolution experiments will make use of optical rotation and circular dichroism spectra to explore the influence of the chiral resolving agent on the ratio of drug enantiomers in solution. Ethics Application Requirements: None required. Key References: 1. Farina, A.; Meille, S. V.; Messina, M. T.; Metrangolo, P.; Resnati, G.; Vecchio, G. Angew. Chem. Int. Ed. 1999, 38, 2433–2436. 2. Appelt, A.; Willis, A. C.; Wild, S. B. Chem. Comm. 1988, 938–940. 52 Title of Project: Rapid and efficient synthesis of the arsenic containing natural product Arsenicin A, and its incorporation into supramolecular drug delivery systems. (FOR Code/s): 030205 Non-metal Chemistry & 030302 Nanochemistry and Supramolecular Chemistry Supervisor: Nathan Kilah Contact: [email protected] (UWS address TBA) Location of Project: Parramatta Project Background: Arsenic compounds are well known as poisons, but they also have medical applications for the treatment of diseases such as leukaemia (Trisenox®), syphilis (Salvarsan) and African sleeping sickness (melarsoprol). The arsenic containing natural product, Arsenicin A, was isolated in 2006 from a marine sponge, and was identified as the first polyarsenical found in nature. The structure of Arsenicin A was later confirmed by organometallic synthesis and X-ray crystallography. This compound has been shown to have remarkable anticancer properties, showing greater inducement of cell death at lower concentration than the currently prescribed, arsenic-based treatment for promyelocytic leukaemia. The current synthetic method to produce Arsenicin A requires several synthetic and purification steps to obtain relatively small quantities of the product. The further investigation and application of Arsenicin A in chemical biology and medicinal chemistry requires a more rapid and higher yielding synthetic method to be developed. In this project, new methods to prepare Arsenicin A (and derivatives) will be investigated. The primary aim will be to make use of more simple starting materials, and fewer steps, to prepare larger scale quantities of Arsenicin A. The reaction pathways investigated will attempt to mimic pathways and intermediates assumed to occur in the biological synthesis. Further investigations will investigate the binding of Arsenicin A within supramolecular drug delivery structures. Aim of Study: Improved synthesis of the polyarsenical natural product, Arsenicin A and derivatives, investigation of their hydrolysis properties and products in solution, and investigation of their binding within supramolecular drug delivery systems for future anticancer investigations. Methods: Organic and organometallic synthesis, characterisation of new compounds by NMR, MS, elemental analysis and X-ray crystallography. Binding strength experiments will make use of NMR titration techniques. Ethics Application Requirements: None required. Key References: 1. Mancini, I.; Guella, G.; Frostin, M.; Hnawia, E.; Laurent, D.;Debitus, C.; Pietra, F. Chem.–Eur. J. 2006, 12, 8989. 2. Tahtinen, P.; Saielli, G.; Guella, G.; Mancini, I.; Bagno, A. Chem. Eur. J. 2008, 14, 10445. 3. Bagno, A. J. Phys. Org. Chem. 2010, 23, 1016. 4. Lu, D.; Rae, A. D.; Salem, G.; Weir, M. L.; Willis, A. C.; Wild, S. B. Organometallics 2010, 29, 32. 5. Lu, D.; Coote, M.L.; Ho, J.; Kilah, N.L.; Lin, C-Y.; Salem, G.; Weir, M.L.; Willis, A.C.; Wild, S.B.; Dilda, P.J. Organometallics 2012, 31, 1808−1816 53 Title of Project: From smart polymers to anticancer drug carriers (FOR Code/s): Inorganic chemistry – Bioniorganic Chemistry (030201) Macromolecular and Materials Chemistry - Synthesis of Materials (030306) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Feng Li Email: [email protected] Telephone: 9987 Location of Project: Parramatta Project Background Smart polymers such as hyperbranched poly(acrylic acid) and chitosan are being tested for drug delivery. Our colleagues in Marseilles, France, can control the synthesis to obtain a range of branched poly(acrylic acid)s. These polyacrylates are also ‘smart’ polymeric materials; they react to changes in pH, and so does chitosan. Our preliminary results show that polyacrylates are branched [1,2]. They also show that capillary electrophoresis [3] can separate them according to their branching structure [4], while it separates chitosan by its composition [5]. These polymers show promise for anticancer drug delivery. The different strategies to bind the drug to the polymer now need to be compared. The optimal strategy needs to be to a chemically simple process, to minimise the introduction of toxic moieties, to ensure that the bound drug will not leak when the loaded polymer is dissolved at pH 7.5. The loaded polymers will then be decorated with folic acid to ensure the accumulation of the drug carrier in cancerous tumours or poly(ethylene glycol) to prevent immune reactions. These binding reactions will be monitored, when possible online, using capillary electrophoresis methods. Aim of Study: To assess different synthetic pathways to bind anticancer drugs, such as cisplatin, and folic acid to the novel polyacrylates synthesized in Marseilles, as well as to chitosan. Methods: (In)organic synthesis. Capillary electrophoresis. Ethics Application Requirements: Not applicable Key References: [1] Gaborieau, P Castignolles, Size-exclusion chromatography (SEC) of branched polymers and polysaccharides. Analytical and Bioanalytical Chemistry 2011, 399, 1413-1423 [2] P Castignolles, R Graf, M Parkinson, M Wilhelm, M Gaborieau, Detection and quantification of branching in polyacrylates by size-exclusion chromatography (SEC) and melt-state 13C NMR spectroscopy. Polymer 2009, 50, 2373-2383. [3] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 [4] AR Maniego, D Ang, Y Guillaneuf, C Lefay, D Gigmes, JR Aldrich-Wright, M Gaborieau, P Castignolles, Separation of poly(acrylic acid) salts according to the topology using capillary electrophoresis in the critical conditions. Analytical and Bioanalytical Chemistry 2013, 405, 9009 [5] M Mnatsakanyan, JJ Thevarajah, RS Roi, A Lauto, M Gaborieau, P Castignolles, Separation of chitosan by degree of acetylation using simple free solution capillary electrophoresis. Analytical and Bioanalytical Chemistry 2013, 405, 6373-6378 54 Macromolecular & Materials Chemistry 55 Title of Project: Effect of Conductive Carbon on the Structure and Electrochemical Performance of LiMnPO4 Cathode Material (FOR Code/s): 0303 and 0912 Supervisor: Dr Adriyan Milev Email: [email protected] Telephone: x9945 Co-supervisor: A/Prof Kamali Kannangara Email: [email protected] Telephone: x9952 Co-supervisor: Dr Laurel George Email: [email protected] Telephone: x9976 Location of the Project: Parramatta North Project Background After a number of cathode materials were found unsuitable for use in large lithium-ion electric vehicle batteries, lithium transition-metal phosphate (LiMPO4, M= Fe, Mn, Co) is now regarded as the best candidate [1, 2]. The advantages for LiMPO4 when compared to the existing electrodes such as LiCoO2, LiMnO2 include: improved safety through higher resistance to thermal runaway, longer cycle-life, low cost of raw materials, low toxicity, and high thermal stability at fully charged state. So far, only one member of this class, LiFePO4, has been employed in advanced batteries. The research is now focused on the more challenging LiMPO4 (M = Mn, and Co) structures, which have higher theoretical energy density (~700 Wh/kg and ~800Wh/kg, respectively) compared to LiFePO 4 (~580 Wh/kg). The LiMnPO4is currently the most promising cathode material for Li-batteries considering its low cost, environmental safety, high theoretical capacity and operating voltage (4.1 V)achievable within the stability window of well-known carbonate ester-based electrolytes. However, few reported studies have demonstrated less than 50% of the theoretical specific capacity even at low rates [3, 4]. This, along with lower electronic conductivity, (~10−10 Scm−1) means it is difficult to obtain satisfying electrochemical activity. Due to its poor electronic properties addition of conductive phase such as carbon during synthesis is required[5]. It is worth noting that not all carbons are equal because they vary in surface area (from several m2/g to over 1000 m2/g) and bond type (sp2, sp3 or even sp)[6]. Therefore, the selection of conductive carbon is important for the electrochemical performance of the cells containing LiMnPO4. Aim of Study: The overall aim is to improve the electrochemical performance of LiMnPO4 cathode material synthesised by a novel sol-gel method developed at UWS. The specific aims are: 1. To improve the electronic conductivity of the materials by addition of conductive carbons; single type or combination of two different carbon types. 2. To investigate the Li+ diffusion rates. Methods: Two broad strategies will be employed to address the diffusion rate and electronic conductivity issues; one is the reduction of the LiMnPO4 particle size to a nanometre level which would consequently lead to a reduction in the diffusion pathway, both for electrons and Li+ in the phosphate structure. The other strategy is to manufacture LiMnPO4 particles coated with a conductive phase, such as carbon that improves the electronic contact between the crystallites. Sample preparation: Three LiMnPO4 samples containing, 5, 10 and 20 wt % conductive carbons will be prepared according to sol-gel methodology developed at UWS [7]. The methodology allows for easy mixing with carbons during the sol-stage of the sol-gel process and therefore is expected to result in a composite cathode material with improved homogeneity than methods based on solid-state reactions. Characterisation: The samples will be characterised by Calorimetry, Electron Microscopy, Raman and Infrared spectroscopies, X-ray diffraction and Surface area measurements. Electrochemical investigations: Selected samples will be used to prepare Li-battery cathodes which will be used to assemble Li-batteries. The electrochemical performance of the batteries will be investigated by Cyclic Voltammetry 56 and charge/discharge cycling using different charge/discharge rates and electrochemical impedance spectroscopy. Form the electrochemical data the energy densities will be calculated and the Li+ diffusion rates will be estimated. Ethics Application Requirements: N/A Note: Because of the commercial sensitivity of the project the successful Hons applicant will be required to sign a UWS Deed of Assignment. The Deed of Assignment creates important legal obligations in relation to: ownership of intellectual property and non-disclosure agreement. Acknowledgements: The project is part of the activities funded by Australia-India Strategic Research Fund grant (ST060005) and a several UWS and SSH research and infrastructure grants. Key References: [[1] N. Recham, Chem. Mater., 21 (2009) 1096-1107. [2] K. Zaghib, A. Mauger, F. Gendron, C.M. Julien, Ionics, 14 (2008) 271-278. [3] T. Shiratsuchi, S. Okada, T. Doi, J.-i. Yamaki, Electrochimica Acta, 54 (2009) 3145-3151. [4] S.K. Martha, B. Markovsky, J. Grinblat, Y. Gofer, O. Haik, E. Zinigrad, D. Aurbach, T. Drezen, D. Wang, G. Deghenghi, I. Exnar, Journal of The Electrochemical Society, 156 (2009) A541-A552. [5] A. Yamada, S. Chung, K. Hinokuma, J. Electrochem. Soc., 148 (2001) A224-A229. [6] A. Milev, D.M.A.S. Dissanayake, G.S.K. Kannangara, A.R. Kumarasinghe, Physical Chemistry Chemical Physics, 15 (2013) 16294-16302. [7] A.S. Milev, G.S.K. Kannangara, B. Ben-Nissan, M.A. Wilson, J. Phys. Chem. B, 108 (2004) 5516-5521. 57 Title of Project: The design, synthesis and characterisation of platinum(IV) prodrugs using flow chemistry (FOR Code/s): 030302 Nanochemistry and Supramolecular Chemistry & 030605 Solution Chemistry Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Chris Gordon Contact: [email protected] Co-supervisor: Gang Zheng Contact: [email protected] Location of Project: Campbelltown Project Background: Platinum(II) compounds which X2 OAc X2 OH H2 H2 have exceptional anticancer activity have been N N N N * Pt * developed at UWS and form the basis of an Pt * N * N N N international patent. Some compounds have been H2 H2 OAc OH synthesised and insights gained from the structureactivity relationships which have allowed us to make X2 OAc X2 HO modifications to the structure that have resulted in a H2 H2 N N N N steady improvement in anticancer activity, (assessed * * Pt Pt * by in vitro cytotoxicity assay against the L1210 murine * N N N N H2 H2 leukaemia cell line). For example, substitution at the 5 OH OAc or 5, 6 positions of the intercalator, 1,10phenathroline (phen) produces compounds with increased activity. Moreover, when a chiral ancillary ligand, such as 1S,2S-diaminocyclohexane is included a further increase in activity is produced. Aim of Study: To synthesise and characterise novel platinum(IV) complexes using both conventional and flow chemistry. The anticancer activity of the resulting complexes will be assessed as a prelude to their application as prodrugs. Methods: Uses molecular modelling for design, both conventional inorganic and flow chemistry for synthesis, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel platinum(IV) complexes will be synthesised using both conventional and Flow chemistry and characterised using a combination of 1H and 195Pt nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional 1H / 195Pt heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). The biological activity of the synthesised complexes will be undertaken with the assessment of cellular cytotoxicity and interactions with DNA. Ethics Application Requirements: None required Key References: 1. Metal Complexes and Therapeutic uses thereof, Fenton, R.R. and Aldrich-Wright, J.R. International Patent, Application Number PCT/AU02/00167, Oct., 2002 2. Fisher, D. M.; Bedarski, P. J.; Grunert, R.; Turner, P.; Fenton, R. R.; Aldrich-Wright, J. R. Chiral platinum(II) metallointercalators with potent in vitro cytotoxicity activity, ChemMedChem (2007), 2, 488-495. 3. Brodie, C.; Collins, J.G.; Aldrich-Wright, J.R. The biological activity of some square-planar platinum(II) metallointercalators. Journal of the Chemical Society, Dalton Transactions (2004), 1145-1152. 4. Krause-Heuer, A. M.; Grünert, Kühne, R. S.; Buczkowska, M.; Wheate, N. J.; Le Pevelen, D.; Boag, L. R.; Fisher, D. M.; Kasparkova, J.; Malina, J.; Bednarski, P. J. Brabec, Patrick V.; Aldrich-Wright, J. R. (2009) Studies into the mechanism of action of platinum(II) complexes with potent cytotoxicity in human cancer cells. Journal of Medicinal Chemistry, 52, 5474-5484. 5. Talib, J.; Beck, J. L.; Urathamakul, T.; Nguyen, C. D.; Aldrich-Wright, J. R.; Mackay, J. P.; Ralph, S. F. (2009) A mass spectrometric investigation of the ability of metal complexes to modulate transcription factor activity. Chemical Communications, (37), 5546-5548. 6. Fisher, D. M.; Fenton, R. R.; Aldrich-Wright, J.R. In vivo studies of a platinum(II) metallointercalator. Chemical Communications, (2008), 43, 5613-5615. 7. Krause-Heuer, A. M.; Grant, M. P.; Orkey, N.; Aldrich-Wright, J. R. Drug delivery devices and targeting agents for platinum(II) anticancer complexes, Australian Journal of Chemistry. Invited paper (2008), 61, 675-681 58 Title of Project: Synthesising N4-tetradentates for coordination to transition metals (FOR Code/s): 030302 Nanochemistry and Supramolecular Chemistry & 030605 Solution Chemistry Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Chris Gordon Contact: [email protected] Co-supervisor: Allan Torres Contact: [email protected] Location of Project: Campbelltown Project Background: There are three stereochemical types of continuous chain N4tetradentates: planar, non-planar and facultative. Because of their structural inflexibility, planar N4-tetradentates, coordinate all four donor atoms to the metal in the same plane. Nonplanar N4-tetradentates coordinate the four donor atoms tetrahedrally about a metal atom. Facultative N4-tetradentates can coordinate all four donor atoms in either a planar or nonplanar arrangement because of their structural flexibility. The coordination chemistry of facultative ligands, like triethylenetetramine (trien), can offer a considerable range of stereisomers by arranging their donor atoms around a metal atom in several of ways. The factor which may determine the disposition may be considered, they comprise of E-strain which includes all forces defining the conformation of the chelate rings. B-strain refers to steric effects as substituents are added to the individual chelate rings will cause restrictions on the neighbouring chelate rings. C-strain is due to the incompatibility of the positioning of the donor atoms of a ligand. A balanced combination of these three effects determines the topology adopted by a N4-tetradentate ligand on coordination and consequently the stability of the complex. N4-Tetradentates ligands offer unique structural properties and upon coordination to metals symmetrical cis-α and unsymmetrical cis-β-positions (shown in the figure) can form. Aim of Study: To synthesise and characterise N4-tetradentate ligands and subsequently coordinate them metals, such as ruthenium cobalt or platinum(II) and (IV) using both conventional and flow chemistry, before their biological activity is determined. Methods: Uses, molecular modelling for design, both conventional inorganic and flow chemistry for synthesis, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). The biological activity of the synthesised complexes will be undertaken with the assessment of cellular cytotoxicity and interactions with DNA. Ethics Application Requirements: None required Key References: 1. Aldrich-Wright, J. R.; Fenton, R. F.; Greguric, I. D.; Hambley, T. W.; Williams, P. A. The stereospecific synthesis of α-{dipyrido[3,2-a:2'3'-c](6,7,8,9-tetrahydro)phenazine [N,N'-di(2-picolyl)-2,5-dimethyl-2S,5S-diaminocyclohexane] ruthenium(II)} and related β -isomers. Dalton Transactions, (2002), 4666-4671. 2. Aldrich-Wright, J.; Vagg, R. S.; Williams, P. A. Design of chiral picen-based metal complexes for molecular recognition of α- aminoacids and nucleic acids, Coordination Chemistry Reviews (1997), 166, 361-389. 3. Cross, R.J., Farrugia, L.J., Newman, P.D., Peacock, R.D., and Stirling, D. Metal Complexes of New, Chiral N2O2 Tetradentate Ligands. Inorganic Chemistry (1999). 38, 1186-1192. 59 Title of Project: The assembly of halogen bonding helicates in solution. (FOR Code/s): 030302 Nanochemistry and Supramolecular Chemistry & 030205 Non-metal Chemistry Supervisor: Nathan Kilah Contact: [email protected] (UWS address TBA) Location of Project: Parramatta (a) (b) Project Background: Supramolecular chemistry is the study of large Me N molecular assemblies held together by a number of weak, yet highly N N Me specific interactions, and can be considered as a “bottom-up” approach to Me N N N X n n nanotechnology. Supramolecular synthetic targets are often designed for X X A X specific topology, symmetry, shape, or function or with the focus on mimicking the complex self-assembled molecules present within X N N n N nN biological systems. One specific example to be investigated in this project Me N is the mimicry of self-assembled helicates (such as nucleic acids and αhelices of proteins) in solution. This will be investigated through the use of 2D representation of a 3D halogen bonds, an underexplored class of non-covalent interaction. halogen bonding helicate. Halogen bonds are attractive interactions formed between positively polarised halogen atoms (specifically bromine and iodine) and electron rich Lewis bases. These interactions, though similar in strength to hydrogen bonds, are highly directionally dependent, and previous investigations have focused on crystal engineering and liquid crystal applications. This project will examine the application of halogen bonding to the assembly of helicates in solution and in the solid state. Solution phase studies will examine the structure, stability and fluxional properties of these helicates, and will investigate the influence of chiral anions on the helical twist of the halogen bonding structures. Aim of Study: The synthesis of halogen bonding helicates, investigating their properties in solution, and influencing their three dimensional structure through the use of chiral anions. Further areas of investigation included the use of anions as templating agents, and the preparation of larger scale, polymeric structures. Methods: Molecular modelling for helicate design. Modern organic synthesis, including the use of transition metal catalysts, characterisation of new compounds by NMR, MS, elemental analysis, X-ray crystallography and Circular Dichroism experiments. Solution phase characterisation will use NMR technique to examine the size of dissolved molecular assemblies, and the influence of chiral anions on the helicity. Ethics Application Requirements: None required. Key References: 5. Kilah, N. L.; Wise, M. D.; Serpell, C. J.; Thompson, A. L.; White, N. G.; Christensen, K. E.; Beer, P. D. J. Am. Chem. Soc. 2010, 132, 11893–11895. 6. Kilah, N. L.; Wise, M. D.; Beer, P. D. Cryst. Growth Des. 2011, 11, 4565–4571. 7. Farina, A.; Meille, S. V.; Messina, M. T.; Metrangolo, P.; Resnati, G.; Vecchio, G. Angew. Chem. Int. Ed. 1999, 38, 2433–2436. 8. Erdelyl, M. Chem. Soc. Rev. 2012, 41, 3547–3557. 60 Title of Project: Rapid and efficient synthesis of the arsenic containing natural product Arsenicin A, and its incorporation into supramolecular drug delivery systems. (FOR Code/s): 030205 Non-metal Chemistry & 030302 Nanochemistry and Supramolecular Chemistry Supervisor: Nathan Kilah Contact: [email protected] (UWS address TBA) Location of Project: Parramatta Project Background: Arsenic compounds are well known as poisons, but they also have medical applications for the treatment of diseases such as leukaemia (Trisenox®), syphilis (Salvarsan) and African sleeping sickness (melarsoprol). The arsenic containing natural product, Arsenicin A, was isolated in 2006 from a marine sponge, and was identified as the first polyarsenical found in nature. The structure of Arsenicin A was later confirmed by organometallic synthesis and X-ray crystallography. This compound has been shown to have remarkable anticancer properties, showing greater inducement of cell death at lower concentration than the currently prescribed, arsenic-based treatment for promyelocytic leukaemia. The current synthetic method to produce Arsenicin A requires several synthetic and purification steps to obtain relatively small quantities of the product. The further investigation and application of Arsenicin A in chemical biology and medicinal chemistry requires a more rapid and higher yielding synthetic method to be developed. In this project, new methods to prepare Arsenicin A (and derivatives) will be investigated. The primary aim will be to make use of more simple starting materials, and fewer steps, to prepare larger scale quantities of Arsenicin A. The reaction pathways investigated will attempt to mimic pathways and intermediates assumed to occur in the biological synthesis. Further investigations will investigate the binding of Arsenicin A within supramolecular drug delivery structures. Aim of Study: Improved synthesis of the polyarsenical natural product, Arsenicin A and derivatives, investigation of their hydrolysis properties and products in solution, and investigation of their binding within supramolecular drug delivery systems for future anticancer investigations. Methods: Organic and organometallic synthesis, characterisation of new compounds by NMR, MS, elemental analysis and X-ray crystallography. Binding strength experiments will make use of NMR titration techniques. Ethics Application Requirements: None required. Key References: 6. Mancini, I.; Guella, G.; Frostin, M.; Hnawia, E.; Laurent, D.;Debitus, C.; Pietra, F. Chem.–Eur. J. 2006, 12, 8989. 7. Tahtinen, P.; Saielli, G.; Guella, G.; Mancini, I.; Bagno, A. Chem. Eur. J. 2008, 14, 10445. 8. Bagno, A. J. Phys. Org. Chem. 2010, 23, 1016. 9. Lu, D.; Rae, A. D.; Salem, G.; Weir, M. L.; Willis, A. C.; Wild, S. B. Organometallics 2010, 29, 32. 10.Lu, D.; Coote, M.L.; Ho, J.; Kilah, N.L.; Lin, C-Y.; Salem, G.; Weir, M.L.; Willis, A.C.; Wild, S.B.; Dilda, P.J. Organometallics 2012, 31, 1808−1816 61 Title of Project: Characterizing polysaccharides for a better health (FOR Code/s): Medicinal and Biomolecular Chemistry - Characterisation of biological macromolecules (030403) Macromolecular and Materials Chemistry - Physical Chemistry of Materials (030304) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Prof. Kelvin Chan Email: [email protected] Location of Project: Parramatta Project Background Polysaccharides are a major and key component of our diet (starch typically represents 50 % of our energy). Glucomannan is a polysaccharide obtained from Konjac and popular to prepare for example jellies in different Asian countries.[1] Glucomannans have health benefits, as dietary fibers, against for example type II diabetes and obesity. However, the reasons for these benefits are not known at the molecular level. It is thus necessary to characterize glucomannans at the molecular level. Galactomannnans are used as viscosifier in the food industry and other fields. They have similarities in chemical composition to the glucomannans: their characterisation is more advanced but tedious, time-consuming and still plagued by a number of uncertainties.[2] The molecular structure of complex polysaccharides and their molecular motion can be understood through the characterisation by solid-state NMR [3]. Solid-state NMR will be applied to the glucomannans and galactomannans: this characterization is possible without any modification of the sample (no dissolution or any type of modification is necessary). We also have recently showed that (free-solution) capillary electrophoresis can separate polysaccharides according to their composition [4]: the method is new, easy, fast and is applied for the first time to glucomannans and galactomannans. Aim of Study: To characterize ‘real’ glucomannans and galactomannans samples developing new capillary electrophoresis and NMR spectroscopy methods, for applications as healthier food. Methods: Solid-state NMR spectroscopy, Capillary electrophoresis. Ethics Application Requirements: Not applicable Key References: [1] M Chua, K Chan, TJ Hocking, PA Williams, CJ Perry, TC Baldwin, Methodologies for the extraction and analysis of konjac glucomannan from corms of Amorphophallus konjac K. Koch. Carbohydrate Polymers, 2012, 87, 22022210 [2] MA Pollard, R Kelly, PA Fischer, EJ Windhab, B Eder, R Amado, Investigation of molecular weight distribution of LBG galactomannan for flours prepared from individual seeds, mixtures, and commercial samples. Food Hydrocolloids 2008, 22, 1596-1606 [3] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386 [4] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 62 Title of Project: Photo-oxidation of sugars and polysaccharides for their characterization by capillary electrophoresis (FOR Code/s): Organic Chemistry, Free radical chemistry (030301) Macromolecular and Materials Chemistry not elsewhere classified (030399) Analytical Chemistry - Instrumental Methods (excl. Immunological and Bioassay Methods) (030105) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Christopher Fellows Email: [email protected] Telephone: 6773 2470 Location of Project: Parramatta Project Background Carbohydrates make up most of the living world around us. Their identification and quantification is generally sought after in many fields such as food and beverage analysis, plant analysis, fermentation studies and metabolism studies. Current analysis methods are not well adapted to the complexity of polysaccharides and the mixtures of carbohydrates derived from them. We have shown that free-solution capillary electrophoresis offers the possibility of simple and robust separations for monosaccharides (such as from plant fibers) [1] or polysaccharides (such as gellan gums [2] and chitosan [3]). The method has a high potential, but the sensitivity of the detection is relatively low for many important polysaccharides such as starch, glucomannans, galactomannans or chitosan. Monosaccharide detection is possible, and highly sensitive through a photo-oxidation process taking place directly in the capillary window. The aim of this project is to apply this photo-oxidation to key polysaccharides chitosan, starch, glucomannans and galactomannans and compare the results to polyol models such as poly(vinyl alcohol). The influence of the addition of photo-oxidant, such as a radical photo-initiator,[4] will be studied, exploring the possibilities of this breakthrough in detection sensitivity. Aim of Study: To better understand the photo-oxidation of sugars and to improve the detection of sugars and polysaccharides with capillary electrophoresis. Methods: Capillary electrophoresis, Photochemistry, Computational chemistry. Ethics Application Requirements: Not applicable Key References: [1] JD Oliver, M Gaborieau, EF Hilder, P Castignolles, Simple and robust determination of monosaccharides in plant fibers in complex mixtures by capillary electrophoresis and high performance liquid chromatography. Journal of Chromatography A, 2013, 1291, 179-186 [2] DL Taylor, CJ Ferris, AR Maniego, P Castignolles, M in het Panhuis, M Gaborieau, Characterization of gellan gum by capillary electrophoresis. Australian Journal of Chemistry, 2012, 55, 1156-1164 [3] M Mnatsakanyan, JJ Thevarajah, RS Roi, A Lauto, M Gaborieau, P Castignolles, Separation of chitosan by degree of acetylation using simple free solution capillary electrophoresis. Analytical and Bioanalytical Chemistry 2013, 405, 6373-6378 [4] JD Oliver, AA Rosser, CM Fellows, Y Guillaneuf, JL Clement, M Gaborieau, P Castignolles, Understanding and improving direct UV detection of monosaccharides and disaccharides in free solution capillary electrophoresis. Analytica Chimica Acta 2014, 809, 183 63 Title of Project: Towards high quality bioplastics (FOR Code/s): Macromolecular and Materials Chemistry – Synthesis of Materials (030306) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Aurelia Charlot Email: [email protected] Location of Project: Parramatta Project Background It is desirable to replace materials derived from oil, such as current plastics, by new ones derived from renewable resources such as cellulose or galactomannans. Cellulose is a significant waste from agriculture, while galactomannans like guar gums are an additive used in the food industry whose resources are largely under-used [1,2]. This is due to the poor intrinsic mechanical properties of these polysaccharides as well as their high sensitivity to moisture. These polysaccharides are often chemically modified to adjust performance to the level of current plastics. Polysaccharides consist of molecules with different types of saccharide units (glucose, galactose, mannose), different molecular weights and different topologies: linear chains or branched ones. The chemical modification improves the properties but also adds to the complexity of the molecules. The elucidation of their structure is needed for the scientific design of bioplastics. We collaborate with Dr Aurelia Charlot and Prof Etienne Fleury (INSA, Lyon, France) to answer these fundamental questions. This project has a strong potential to lead to industrial collaborations. Aim of Study: To characterise and assess potential bioplastics derived from cellulose or galactomannans. With solidstate NMR [3] we will reveal the interplay between molecular structure and molecular motions, and explore the crucial role of moisture. We will use capillary electrophoresis (in the critical conditions) [4] to separate compounds with different compositions and different degrees of modification. Methods: Capillary electrophoresis, Solid-state NMR spectroscopy. Ethics Application Requirements: Not applicable Key References: [1] C Lacroix, E Sultan, E Fleury, A Charlot, Functional galactomannan platform from convenient esterification in imidazolium-based ionic liquids. Polymer Chemistry 2012, 3, 538-46 [2] G Mangiante, P Alcouffe, B Burdin, M Gaborieau, E Zeno, M Petit-Conil, J Bernard, A Charlot, E Fleury, Green nondegrading approach to alkyne-functionalized cellulose fibers and biohybrids thereof: synthesis and mapping of the derivatization. Biomacromolecules 2013, 14, 254-63 [3] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386 [4] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 64 Title of Project: Characterization of pH-responsive polymers to better understand controlled polymerization (FOR Code/s): Analytical Chemistry – Separation Science (030108) Macromolecular and Materials Chemistry – Polymerisation Mechanisms (030305) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Franck d’Agosto Email: [email protected] Location of Project: Parramatta Project Background pH-responsive polymers see their solubility in water greatly affected by pH. They are commonly used to stabilize colloids. The team of Prof. Bernadette Charleux and Dr Franck d’Agosto (University Lyon 1, France) developed a technology to control the polymerization of a variety of monomers in emulsion [1]. This process relies on the use of stable radical, nitroxides. The visit to UWS of Emilie Groison, PhD student enrolled in Lyon, France showed the potential of the capillary electrophoresis method we develop in our group to separate the pH-responsive stabilizer. Aim of Study: The aim of the project is investigate the potential of capillary electrophoresis [2-3] to separate these complex samples. The samples are synthesized in Lyon. The project consists in separating them and characterizing them to finally explore the mechanism of the nitroxide-mediated polymerization process. Methods: Capillary electrophoresis. Ethics Application Requirements: Not applicable Key References: [1] E Groison, S Brusseau, F D’Agosto, S Magnet, R Inoubli, L Couvreur, B Charleux, Well-defined amphiphilic block copolymer nanoobjects via nitroxide-mediated emulsion polymerization. ACS Macro Letters, 2012, 1, 47-51 [2] M Gaborieau, TJ Causon, Y Guillaneuf, EF Hilder, P Castignolles, Molecular weight and tacticity of oligoacrylates by capillary electrophoresis-mass spectrometry. Australian Journal of Chemistry 2010, 63, 1219-26 [3] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 65 Title of Project: From smart polymers to anticancer drug carriers (FOR Code/s): Inorganic chemistry – Bioniorganic Chemistry (030201) Macromolecular and Materials Chemistry - Synthesis of Materials (030306) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Feng Li Email: [email protected] Telephone: 9987 Location of Project: Parramatta Project Background Smart polymers such as hyperbranched poly(acrylic acid) and chitosan are being tested for drug delivery. Our colleagues in Marseilles, France, can control the synthesis to obtain a range of branched poly(acrylic acid)s. These polyacrylates are also ‘smart’ polymeric materials; they react to changes in pH, and so does chitosan. Our preliminary results show that polyacrylates are branched [1,2]. They also show that capillary electrophoresis [3] can separate them according to their branching structure [4], while it separates chitosan by its composition [5]. These polymers show promise for anticancer drug delivery. The different strategies to bind the drug to the polymer now need to be compared. The optimal strategy needs to be to a chemically simple process, to minimise the introduction of toxic moieties, to ensure that the bound drug will not leak when the loaded polymer is dissolved at pH 7.5. The loaded polymers will then be decorated with folic acid to ensure the accumulation of the drug carrier in cancerous tumours or poly(ethylene glycol) to prevent immune reactions. These binding reactions will be monitored, when possible online, using capillary electrophoresis methods. Aim of Study: To assess different synthetic pathways to bind anticancer drugs, such as cisplatin, and folic acid to the novel polyacrylates synthesized in Marseilles, as well as to chitosan. Methods: (In)organic synthesis. Capillary electrophoresis. Ethics Application Requirements: Not applicable Key References: [1] Gaborieau, P Castignolles, Size-exclusion chromatography (SEC) of branched polymers and polysaccharides. Analytical and Bioanalytical Chemistry 2011, 399, 1413-1423 [2] P Castignolles, R Graf, M Parkinson, M Wilhelm, M Gaborieau, Detection and quantification of branching in polyacrylates by size-exclusion chromatography (SEC) and melt-state 13C NMR spectroscopy. Polymer 2009, 50, 2373-2383. [3] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 [4] AR Maniego, D Ang, Y Guillaneuf, C Lefay, D Gigmes, JR Aldrich-Wright, M Gaborieau, P Castignolles, Separation of poly(acrylic acid) salts according to the topology using capillary electrophoresis in the critical conditions. Analytical and Bioanalytical Chemistry 2013, 405, 9009 [5] M Mnatsakanyan, JJ Thevarajah, RS Roi, A Lauto, M Gaborieau, P Castignolles, Separation of chitosan by degree of acetylation using simple free solution capillary electrophoresis. Analytical and Bioanalytical Chemistry 2013, 405, 6373-6378 66 Title of Project: Polysaccharide-water interactions by solid-state NMR (FOR Code/s): Physical chemistry – Structure Chemistry and Spectroscopy (030606) Macromolecular and Materials Chemistry - Physical Chemistry of Materials (030304) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Robert Graf Email: [email protected] Location of Project: Parramatta Project Background Starch is the main source of energy in human diet, as it is a major component of wheat, maize, potatoes and rice. It is renewable, cheap and biodegradable, and therefore has major applications in the paper, pharmaceutical and textile industries. Starch is a chemically simple polymer (a homopolymer of glucose) but it has a very complex macromolecular (branched) and supramolecular structure, with six identified hierarchical levels, on scales ranging from nm to mm. Its hydrogen-bonding capacity, provided by three hydroxyl groups per glucose unit, is crucial for its solid-state structure as well as its behaviour in solution. Starch granules contain water molecules, which are an integral part of the semi-crystalline structure. Starch-water interactions play an important role in the mechanical properties of starch-based bioplastics. They also define the first stages of cooking of starch, and therefore are expected to play a role in diet-related diseases such as obesity and diabetes. Solid-state Nuclear Magnetic Resonance (NMR) is an invaluable tool in the study of polymer materials such as polysaccharides: it yields local information on their structure and dynamics [1,2]. This project will build on the expertise of Dr Marion Gaborieau in solid-state nuclear magnetic resonance (NMR) of native and functionalized polysaccharides. Aim of Study: In this study, the local dynamics of starch and residual water will be investigated on the molecular level as a function of sample temperature by solid-state nuclear magnetic resonance (NMR) methods. The study will also be extended to other polysaccharides and real food such as breakfast cereals and rice. This will shed light onto hydrogen bonding capacity of starch (as a model polysaccharide) and its interactions with water. It will help elucidate the poorly-understood endothermic transition observed by differential scanning calorimetry for many polysaccharides [3]. Methods: Solid-state NMR spectroscopy, differential scanning calorimetry (DSC). Ethics Application Requirements: Not applicable Key References: [1] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386 [2] G Mangiante, P Alcouffe, B Burdin, M Gaborieau, E Zeno, M Petit-Conil, J Bernard, A Charlot, E Fleury, Green nondegrading approach to alkyne-functionalized cellulose fibers and biohybrids thereof: synthesis and mapping of the derivatization. Biomacromolecules 2013, 14, 254-263 [3] IAM Appelqvist, D Cooke, MJ Gidley, SJ Lane, Thermal properties of polysaccharides at low moisture: An endothermic melting process and water-carbohydrate interactions. Carbohydrate Polymers 1993, 20, 291-299 67 Title of Project: Smart polymers as the additives of the future (FOR Code/s): Macromolecular and Materials Chemistry – Polymerisation mechanisms (030305) Analytical Chemistry - Separation Science (030108) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Prof Mathias Destarac Email: [email protected] Location of Project: Parramatta Project Background ’Smart’ polymeric materials react to changes in temperature or pH. These ‘smart’ polymers are intensively researched for use in drug delivery, water purification and more. The ‘smart’ behaviour of these materials is making their characterization difficult by common liquid chromatography methods. The team of Prof. Mathias Destarac (University Paul Sabatier, Toulouse, France) developed a new technology to synthesize some complex polymers in which part of the polymer chain is cationic, while the other part is neutral and thermoresponsive [1]. The cationic part ensures this polymer has great adhesive properties on a number of substrates. The thermoresponsive properties mean that the materials is water-soluble at low temperature but not at high temperature. Aim of Study: The characterization of these polymers has been extremely challenging up to now due to the presence of the charges. We propose to use this charge at our advantage and separate the polymers using an electric field, i.e. using capillary electrophoresis [2]. The self-assembly of these polymers leads to powerful and fascinating structures that could be characterized using solid-state NMR [3]. Methods: Capillary electrophoresis, solid-state NMR spectroscopy. Ethics Application Requirements: Not applicable Key References: [1] M Destarac, On the critical role of RAFT agent design in reversible addition-fragmentation chain transfer (RAFT) polymerization. Polymer Reviews 2011, 51, 163-187 [2] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 [3] W Gu, M Gaborieau, VT Huynh, PL de Souza, MH Stenzel, Functionalization of microspheres with malonates using Michael addition as a pathway to create a drug delivery system for platinum drugs for the treatment of liver cancer. Polymer 2011, 52, 5993-6002 68 Title of Project: Characterisation of functionalised chitosan films (for cell culture) (FOR Code/s): Physical Chemistry – Colloid and Surface chemistry (030603) Biochemistry and Cell Biology (0601) Macromolecular and Materials Chemistry - Physical Chemistry of Materials (030304) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Richard Wuhrer Email: [email protected] Telephone: 9089 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Location of Project: Parramatta Project Background Chitosan is an amazing polymer derived from chitin, the main component of crab or prawn shells and many others. On top of being a renewable and sustainable material, chitosan is bacteriostatic and it has thus a great potential to produce films for cells culture.[1] Our research group has developed a methodology to functionalise chitosan films with small biomolecules and quantify the grafting and these biomolecules. The surface of the film and its functionality are the key to avoid film-to-film variability in the cell culture. Scanning Electron Microscopy (SEM) allows probing the morphology of the film surface. The functionalization can be assessed through SIMS-ToF. A more in-depth analysis of the roughness is possible through Atomic Force Microscopy (AFM). All these powerful characterisation methods are available at UWS. Aim of Study: To characterise the roughness and functionalization of a chitosan film surface. Methods: SEM, SiMS ToF, AFM Ethics Application Requirements: Not applicable Key References: [1] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis and X-ray diffraction. Biomacromolecules 2011, 12, 1380. 69 Title of Project: Structure of polyamides and adhesive properties (FOR Code/s): Macromolecular and Materials Chemistry – Chemical characterisation of Materials (030301) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Richard Wuhrer Email: [email protected] Telephone: 9089 Location of Project: Parramatta Project Background Polyamides have been a very successful industrial story since their discovery in the 1930s by the company Dupont de Nemours. Nylon is likely the most well-known member of this family. The difficulties to characterise these polymers may have limited the expansion of this family. One key innovation has however been the use of fatty acids (from paper production for example) to produce polyamides for industrial adhesives (hot-melt adhesives). These polyamides come from a sustainable and renewable source, but they are then complex in terms of chemical structure, namely composition. We have shown that capillary electrophoresis (CE) is a simple and robust method to characterise the composition of complex polysaccharides.[1,2] This method will be applied to polyamide subjected to acid hydrolysis. The resulting samples will also be analysed with solution-state NMR spectroscopy. The hydrolysis should only lead to depolymerisation but other degradation processes may also take place. Adhesives, as most industrial materials, are loaded with a number of additives. To investigate potential degradation and the presence of additives, solid state characterisation methods will also be applied: solid-state NMR [3] and ATR IR spectroscopies. This project can lead to collaborations and job opportunities in various manufacturing companies. Aim of Study: To relate the chemical composition of hot meld adhesives to their adhesive properties. Methods: Capillary electrophoresis, solution-state and solid state NMR spectroscopies, ATR IR spectroscopy Ethics Application Requirements: Not applicable Key References: [1] JD Oliver, M Gaborieau, EF Hilder, P Castignolles, Simple and robust determination of monosaccharides in plant fibers in complex mixtures by capillary electrophoresis and high performance liquid chromatography. Journal of Chromatography A 2013, 1291, 179-186 [2] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 [3] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386 70 Title of Project: What is a true solution (of chitosan)? Does it exist? And why does it matter? (FOR Code/s): Macromolecular and Materials Chemistry - Physical Chemistry of Materials (030304) Analytical Chemistry - Separation Science (030108) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Michael O’Connor Email: m.o'[email protected] Telephone: 3902 Location of Project: Mainly Parramatta, but also Campbelltown for cell culture Project Background Chitosan is an amazing polymer derived from chitin, the main component of crab or prawn shells and many others. On top of being a renewable and sustainable material, chitosan is bacteriostatic and it has thus a great potential to produce films for cell culture or transplantation and regenerative medicine.[1] Our research group has developed a methodology to functionalise chitosan films with small biomolecules and quantify the grafting and these biomolecules.[2] However, the homogeneity of the film surface currently needs to be improved. The films are obtained by casting a chitosan “solution” and evaporating the solvent. Preliminary investigations show that the heterogeneity of the chitosan film surface may arise from the presence of aggregates in the chitosan “solution”. Pressure mobilisation or capillary electrophoresis can give a quick assessment of the kinetics of dissolution of the chitosan available from different sources. This can be completed by time-resolved NMR spectroscopy [3] and then quantitative NMR spectroscopy [4]. Different methods to cast the films will also be investigated and compared. Cells will be cultured on these films to assess the homogeneity of the film surface as well as the film-to-film variability. By identifying ways of improving chitosan film production, this project will advance the fields of both polymer chemistry and regenerative medicine. Aim of Study: To obtain a true chitosan solution for reproducible casting of chitosan film with homogenous surfaces Methods: Capillary electrophoresis, NMR spectroscopy, Cell culture Ethics Application Requirements: Not applicable Key References: [1] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis and X-ray diffraction. Biomacromolecules 2011, 12, 1380 [2] C Lefay, Y Guillaneuf, G Moreira, JJ Thevarajah, P Castignolles, F Ziarelli, E Bloch, M Major, L Charles, M Gaborieau, D Bertin, D Gigmes, Heterogeneous modification of chitosan via nitroxide-mediated polymerization. Polymer Chemistry 2013, 4, 322 [3] A Dona, C-WW Yuen, J Peate, RG Gilbert, P Castignolles, M Gaborieau, A new NMR method for directly monitoring and quantifying the dissolution kinetics of starch in DMSO. Carbohydrate Research 2007, 342, 2604 [4] S Schmitz, AC Dona, P Castignolles, RG Gilbert, M Gaborieau, Assessment of the Extent of Starch Dissolution in Dimethyl Sulfoxide by 1H NMR Spectroscopy. Macromolecular Bioscience 2009, 9, 506. 71 Title of Project: Importance of branching and debranching in anticancer drug carriers (FOR Code/s): Biological Sciences, Analytical Biochemistry (060101) Macromolecular and Materials Chemistry - Synthesis of Materials (030306) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Prof. Jens Coorssen Email: [email protected] Telephone: 3802 Location of Project: Parramatta Project Background Poly(acrylic acid) is used in our research group to produce potential anticancer drug carriers. This polymer is smart: it reacts to pH changes thus releasing the drug in acidic media such as tumours. Large molecule such as polymers can either have a linear structure or a branched one (tree-like). We have shown that poly(acrylic acid) is branched [1] and this is beneficial to ensure that the drug does not leak out of the polymer in physiological conditions. The branched structure controls the release and retention of the drug. To understand these, the size (molar mass distribution) of the branches needs to be determined. In addition, the poly(acrylic acid) drug carrier is too large to be eliminated by the body after the drug delivery. Poly(acrylic acid) was designed to be debranched into small fragments on a longer time frame. The kinetics of debranching in physiological conditions will be investigated to ensure that the drug carrier does not accumulate for example in the kidneys. Aim of Study: To debranch a branched poly(acrylic acid) to characterise the branches and assess the potential of this poly(acrylic acid) for anticancer drug delivery. Methods: Capillary Electrophoresis, NMR spectroscopy Ethics Application Requirements: Not applicable Key References: [1] A Maniego, D Ang, Y Guillaneuf, C Lefay, D Gigmes, J Aldrich-Wright, M Gaborieau, P Castignolles, Separation of poly(acrylic acid) salts according to topology using capillary electrophoresis in the critical conditions. Analytical and Bioanalytical Chemistry 2013, 405, 9009 72 Field of Research: Title of Project: 0204 0303 0306 Supervisor: Decode Nature’s Way of Detoxification – NMR Studies on Dissolved Organic Matter in Australian Aquatic Systems Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Co-supervisor: Prof William S Price Campus project is offered and conducted: Email: [email protected] Telephone: 4620 3336 Campbelltown Background (max 500 words) Like ourselves, mother nature has many methods for detoxification. Dissolved organic matter (DOM) plays a major role in natural detoxification in aquatic systems. In fresh water, many harmful versions of heavy metals (e.g., methylmercury) latch onto DOM then are more likely broken down into harmless compounds by sunlight. In sea water, however, these nasty metal complexes tend to latch onto salt (i.e., sodium chloride) instead of DOM and therefore are far more likely accumulated through the food chain, according to studies by a US researcher. In this study, the key chemical components of the various DOM in Australian aquatic systems will be identified, their roles in the natural detoxification will be revealed, and environmental factors (e.g., salt) affecting the detoxification process will be identified. (Would suit students interested in Biology/Chemistry/NMR/Physics) Aim of Study: To unveil the role of each key chemical component of DOM in natural aquatic detoxification. Methods: Nuclear Magnetic Resonance Spectroscopy, Fluorescence Spectroscopy, Size Exclusion Chromatography Ethics Application Requirements: Not Applicable Nuclear Magnetic Resonance Spectroscopy, Fluorescence Spectroscopy, Size Exclusion Chromatography Key References: 4. G. Zheng and W.S. Price, Direct hydrodynamic radius measurement on dissolved organic matter in natural waters using diffusion NMR. Environ. Sci. Tech., 2012. 46(3): p. 1675-1680. 5. G. Zheng, T. Stait-Gardner, P.G. Anil Kumar, A.M. Torres, and W.S. Price, PGSTE-WATERGATE: An STE-based PGSE NMR sequence with excellent solvent suppression. J. Magn. Reson., 2008. 191: 159-163. 6. G. Zheng and W.S. Price, Solvent signal suppression in NMR. Prog. Nucl. Magn. Reson. Spec., 2010. 56: 267-288. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 73 Field of Research: Title of Project: 0204 0303 0304 0306 Expanding the Boundaries and Applications of Diffusion NMR Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Allan Torres Email: [email protected] Telephone: 4620 3459 Campus project is offered and conducted: Campbelltown Background (max 500 words) Diffusion NMR is routinely used to study various molecular properties, and interactions occurring in solution. This technique is also valuable in MRI as it can be used to probe microscopic structures in biological tissues. Recently, longlived singlet spin states have been used in NMR diffusion and diffusion-diffraction studies. Unlike regular spin coherences, singlet spin states have significantly longer lifetimes on the order of tens of seconds to a minute making it feasible to study extremely slowly diffusing molecules. In diffusion-diffraction studies, long lived singlet states can potentially be useful for probing structures with larger characteristic distances. In this project, the restricted diffusion of test molecules in glass and flexible silica capillaries will be investigated by utilising singlet spin states and various NMR coherences. The feasibility of performing NMR diffusion experiments in a single capillary with internal diameter of 10-200 micrometers will also be studied. (Would suit students interested in NMR/Physical Chemistry/Physics) Aim of Study: To characterise NMR diffusion in capillaries using various spin coherences and singlet spin states. Methods: Nuclear Magnetic Resonance Spectroscopy Ethics Application Requirements: Not Applicable Key References: 5. M. Carravetta and M.H. Levitt, Long-lived nuclear spin states in high-field solution NMR. J. Am. Chem. Soc. 126 (2004) 6228-6229. 6. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 7. N.N. Yadav, A.M. Torres and W.S. Price, NMR q-space imaging of macroscopic pores using singlet spin states. J. Magn. Reson. 204 (2010) 346-348. 8. A.M. Torres, B. Ghadirian and W.S. Price, Diffusion-diffraction using singlet spin states and various NMR coherences in a J-coupled AX spin system. RSC Advances 8 (2012) 3352-3360. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 74 Field of Research: Title of Project: 0204 0299 0303 0306 Investigating Phantoms and Biostructures using NMR/MRI Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Tim-Stait-Gardner Email: [email protected] Telephone: 4620 3216 Dr Scott A Willis Campus project is offered and conducted: [email protected] 4620 3114 Campbelltown Background (max 500 words) Biological tissue is not just an amorphous arrangement of cells. Indeed most tissue has an underlying structure composed of microscopic components as in muscle fibres or, as has more recently been realised, fibre tracts in brain tissue. Although the tracts might ultimately be macroscopic, they are composed of microscopic components. Such structures are not only involved in normal biological function, but also in diseased states, such as multiple sclerosis, epilepsy, and Alzheimer’s disease. Traditional techniques used to visualise such structures are not only limited in their application, but often these methods are invasive and tedious. In this project new NMR/MRI diffusion methods will be used to characterise microstructure of suitable phantom (e.g., gels, capillaries) and tissue samples on a microscopic scale well below the resolution that is achievable using standard MRI sequences. In addition, the student would participate in the development of new NMR/MRI methods aimed at elucidating sample microstructure. (Would suit students interested in Biology/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To characterise a variety of microstructures in phantom samples (e.g., gels, capillaries) as well as tissues (e.g., brain, muscle) and to participate in the development of new NMR techniques with this purpose. Methods: Nuclear Magnetic Resonance Spectroscopy and Imaging Ethics Application Requirements: Not Applicable Key References: 7. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 8. S. Mori, J. Zhang, Principles of diffusion tensor imaging and its applications to basic neuroscience research, Neuron 51 (2006) 527-539. 9. P. Callaghan, Principles of Nuclear Magnetic Resonance Microscopy, Oxford University Press 1994. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 75 Field of Research: Title of Project: 0204 0299 0303 0306 Investigating Restricted Diffusion using NMR Techniques Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Bahman Ghadirian Email: [email protected] Telephone: 4620 3216 Campus project is offered and conducted: Campbelltown Background (max 500 words) Modelling self-diffusion in complicated geometries is of fundamental importance in many areas of science including medicine. Modelling diffusion-controlled reactions - which occur widely in chemical, and biochemical systems, and nuclear magnetic resonance diffusion experiments in bounded systems, provide many prominent examples of where such modelling is required. Using a simple cellular system as an example, a reacting species diffuses to the enzymatic membrane and then reacts in some way, being either transformed into a product, becoming bound to the surface or transported through the surface. The nature of the interaction at the surface determines the boundary conditions in the modelling. Presently only solutions for some simple geometries are available. This is a serious impediment as most real-world structures that chemical reactions occur in have complicated geometries. Thus, there is a need to develop techniques for modelling diffusive processes near surfaces which are applicable to different geometries and arbitrary boundary conditions. (Would suit students interested in Biology/Chemistry/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To develop theoretical and experimental method for investigating diffusion in restricted systems and studying their application. Methods: Analytical modelling and numerical computer programming in Mathcad or Matlab, and testing the models using NMR experiments. Ethics Application Requirements: Not Applicable Key References: 13. C. H. Neuman, J. Chem. Phys. 60, 4508 (1974). 14. S. D. Traytak and W. S. Price, J. Chem. Phys. 127, 184508 (2007). 15. G. A. Truskey, F. Yuan, and D. F. Katz, Transport Phenomena in Biological Systems. (Pearson, London, 2004). 16. W. S. Price, NMR Studies of Translational Motion. (Cambridge University Press, Cambridge, 2009). 17. D. G. Duffy, Mixed Boundary Value Problems. (Chapman & Hall / CRC, New York, 2008). 18. B. Ghadirian, A. M. Torres, N. N. Yadav, and W. S. Price. J. Chem. Phys. 138:094202-1-094202-11 (2013). This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 76 Title of Project: Self‐Assembly of Coordination Cages (FOR Code/s): 0303 Macromolecular and Materials Chemistry Supervisor: Dr Feng Li Email: [email protected] Telephone: 96859987 Co‐supervisor: Prof. Len Lindoy (USyd) Email: [email protected] Telephone: Campus project is offered and conducted: Parramatta Background (max 500 words) The self-assembly of coordination cages has continued to receive considerable attention over the past decade,1,2 because of their many potential applications in gas adsorption, drug delivery, catalysis, magnetic materials, host-guest phenomena and synthetic membranes for ion channels. Although a number of coordination cage types have been developed, the design and successful construction of these systems, particularly those with heteronuclear coordination motifs (figure 1), still represents a significant challenge. Aim of Study: The design of suitable organic ligands and the selection of the correct metal ions for favoring structure-specific self-assembly play important roles in the construction of discrete coordination cages. Thus much attention in this project will be focused on the synthetic approach and the structural control of coordination architectures, especially for those with multidimensional structures. This will elucidate fundamental aspects of metallo-supramolecular chemistry (including the role that both metal ions and organic species may play in the assembly process), factors influencing host-guest inclusion behaviour and the nature of electronic/magnetic interactions between spin-crossover and magnetic coupling energies. Methods: Figure 1. The X-ray single-crystal structure of heterometallic cube 1. a) Perspective view emphasizing one of the C4 symmetry axes; b) view down one of the C3 axes; The large yellow sphere indicates the large cavity. c) Space-filling model of the structure. Solvent molecules, counter ions and hydrogen atoms are omitted for clarity. Three synthetic procedures have been successfully exploited for the construction of discrete heteronuclear coordination architectures: 1) exploitation of the inherent coordination properties between ligands and different metal ions for the metal-directed assembly of discrete metallo-supramolecular architectures; 2) formation of discrete metallo-assemblies preorganised for binding a second metal ion, or ions, to yield discrete heterometallic architectures; 3) employing preformed metalloligands functionalised for use as building blocks reacting with additional metal ions and sometimes extra ligands Ethics Application Requirements: N/A Key References: 1. F. Reichel, J. K. Clegg,.K. Gloe, K.. Gloe, J. J. Weigand, J. K. Reynolds, C.-G. Li, J. R. Aldrich-Wright, C.J. Kepert, L.F. Lindoy, H.-C. Yao and F. Li, Inorganic Chemistry, 2014, 688-690. 2. J. K. Clegg, F. Li, K. A. Jolliffe, G. V. Meehan and L. F. Lindoy, Chem. Commun., 2011, 6042-6044. 77 Title of Project: Metal Directed Assembly of Discrete Supramolecular Systems (FOR Code/s): 0303 Macromolecular and Materials Chemistry Supervisor: Dr Feng Li Email: [email protected] Telephone: 96859987 Co‐supervisor: Prof. Janice Aldrich‐Wright Email: J.Aldrich‐[email protected] Telephone: 46203218 Campus project is offered and conducted: Parramatta Background (max 500 words) The metal-ion directed assembly of discrete molecular architectures, and especially those with interesting supramolecular topologies, has received very considerable attention over recent years, because of their specific applications in recognition, catalysis, magnetic materials and synthetic membranes for ion channels (see left).1-3 Yet the rational design and synthesis of discrete coordination architectures or polymeric coordinations still remains a great challenge. The ultimate aim of metallo-supramolecular systems is to control the structure of the target product with expected properties and functions. These include novel redoxactive, magnetism, photoactive, conductive (including superconductive), catalytic and non-linear optical properties. Aim of Study: The design of suitable organic ligands and the selection of the correct metal ions for favoring structure- specific selfassembly play important roles in the construction of discrete coordination architectures. Thus much attention in this project will be focused on the synthetic approach and the structural control of coordination architectures, especially for those with multidimensional structures. The organic components to be employed all incorporate ߚdiketonate, pyridylpyrazole and/or imidazole schiff base sites - motivated in part by the availability of the extremely well documented metal coordination behaviour of these ‘classical’ coordination entities. Furthermore, characterization and functionality of such systems will be investigated for specific applications in host-guest chemistry and spin-crossover (SCO) studies. This will elucidate fundamental aspects of metallo-supramolecular chemistry (including the role that both metal ions and organic species may play in the assembly process), factors influencing host-guest inclusion behaviour and the nature of electronic/magnetic interactions between spin-crossover and magnetic coupling energies. Methods: To employ directed assembly procedures, stepwise syntheses and template controls for constructing innovative nanometre-scale materials. Ethics Application Requirements: N/A Key References: 1. F. Li, J. K. Clegg, R. B. Macquart, G. V. Meehan and L. F. Lindoy, Nature Commun., 2011, 2: 205. 2. F. Li, J. K. Clegg, L. Goux-Capes, G. Chastanet, D. M. D'Alessandro, J.-F. Létard, and C. J. Kepert, Angew. Chem. Int. Ed., 2011, 50, 2820-2823. 3. F. Li, J. K. Clegg, D. Price, and C. J. Kepert, Inorg. Chem., 2011, 50, 726-728. 78 Title of Project: Discrete Interlocked/Intertwined Supramolecular Assemblies (FOR Code/s): 0303 Macromolecular and Materials Chemistry Supervisor: Dr Feng Li Email: [email protected] Telephone: 96859987 Co‐supervisor: Prof. Len Lindoy (USyd) Email: [email protected] Telephone: Campus project is offered and conducted: Parramatta Background (max 500 words) In the realm of supramolecular chemistry, finite nano-scale interlocked/intertwined metallo-supramolecular ensembles with interesting and beautiful molecular structures have received very considerable attention over recent years (See below).1-3 Such metallo-architectures range from large metal protein to a small number of intricately interwoven structures that bridge the boundaries between Art and Science. These ensembles, which typically form on the nanometer scale, display both considerable beauty and applications. However, the generation of new structures of this type has remained a very significant synthetic challenge. A condition for the rational strategies of such metal organic structures is that the metal ion(s) and organic component(s) display the required steric and electronic complementarity to promote formation of the molecular architecture of interest. Aim of Study: The application of cation and/or anion templated syntheses to the design and construction of new practical molecular devices and machines, including sensors, (opto)electronic devices (including electronic components ranging from transistors to logic gates) and enzyme-like catalysts remains a significant intellectual and practical challenge. To probe the construction of novel molecular devices, which show molecular movement of interlocked/intertwined constituent parts that can be triggered by cation and/or anion binding controls, is anticipated to lead to novel supramolecular assemblies for practical applications in molecular memory and molecular machines. The proposed interlocked supramolecular systems could also contribute to the development of nanoscale molecular machines that, for example, might mimic the role of sophisticated biomolecular entities. Methods: The application of cation and/or anion templated syntheses to the design and construction of new practical molecular devices and machines Ethics Application Requirements: N/A Key References: 1. L. F. Lindoy, & I. M. Atkinson, Self-Assembly in Supramolecular Systems (Royal Society of Chemistry, 2000). 2. J.- P. Sauvage, & C. Dietrich-Buchecker, eds Molecular Catenanes, Rotaxanes and Knots (Wiley-VCH, 1999). 3. F. Li, J. K. Clegg, R. B. Macquart, G. V. Meehan and L. F. Lindoy, Nature Commun., 2011, 2: 205. 79 Medicinal & Biomolecular Chemistry 80 Title of Project: A fat lot of good: direct analysis of lipids by TLC-MS (FOR Code/s): 030101, 030108, 030405 Supervisor: David Harman Co-supervisor: Jens Coorssen Contact: [email protected] Contact: [email protected] Location of Project: Campbelltown Campus, School of Medicine Project Background: Lipids are fatty, waxy, or oily substances that the body uses for energy and structure. In fact, the walls of the cells in our body are composed largely of a double layer of a type of lipid called a phospholipid. It was previously thought the biological role of lipids was confined to membrane composition, energy storage, thermal insulation and as a dietary source of fat soluble vitamins. However, recently it was discovered that cells use lipids to communicate with each other. Furthermore, lipids are involved in immune system function, tissue inflammation and affect reproduction, metabolism and blood pressure. As a consequence, medical science is now engaged in an intense search for lipid biomarkers (indicators of disease) in order to allow early intervention in otherwise serious illnesses. It is therefore important to determine which types of lipids and how much of each are present in various types of body tissues. This Honours research project is focussed upon the development of methods to identify lipids directly after their separation, using state-of-the art instrumentation. Aim of Study: The main objective is to optimise the analysis of lipids using an established high performance thin layer chromatography (HPTLC) method1 coupled directly to mass spectrometry (MS). The hypothesis is that extraction conditions for different lipid species need to be optimised to achieve high quality, quantitative analyses at high detection sensitivity. Methods: A mixture of phospholipids of known composition will be separated using an established HPTLC technique. Identification of each resolved lipid species will be undertaken by electrospray ionisation MS (ESI-MS) via direct sampling from the TLC plate (Fig. 1) using the Camag TLC-MS interface (Fig. 2). Resolution of parallel standards will enable identification of lipid species as well as quantification of lipids in the test lanes. Methods will be developed to achieve detection, identification and quantification of different lipid species. Finally, the researcher will apply the method to quantitative evaluation of a native tissue extract, thus demonstrating that a ‘lipidome’ analysis is possible using HPTLC-MS. Ethics Application Requirements: No ethics approvals will be required. Key References: 1. M.A. Churchward, D. Brandman, T. Rogasevskaia, and J.R. Coorssen J. Chem. Biol. 2008, 1, 79-87. 2. H. Park, Y. Zhou and C.E. Costello J. Lipid Res. 2014, 55, 773-781. 4. M.L. Dória, C. Z. Cotrim, C. Simões, B. Macedo , P. Domingues, M.R. Domingues and L.A. Helguero J. Cell. Physiol. 2013, 228, 457–468. 5. J. Sherma J. AOAC Internat. 2012, 95, 992-1009 (review). 81 Title of Project: Developing new anticancer drugs using flow chemistry (FOR Code/s): 030201 Bioinorganic Chemistry & 030401 Biologically Active Molecules Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Christopher Gordon Contact: [email protected] Location of Project: Campbelltown Project Background: This project aims to advance a branch of chemistry known as flow-chemistry. This emerging technology has the potential to revolutionize pharmaceutical production by improving quality and reducing chemical waste. However, if flow chemistry is to be embraced by the broader synthetic community a number of significant limitations need to be addressed. Thus the aim of this project is to address a number of these limitations by devising cutting-edge total-flow-synthesis methods by produce a series of platinum(II) compounds which possess exceptional anticancer activity. Aim of Study: To develop a procedure to synthesise and characterise platinum(II) complexes using flow chemistry. Methods: Uses both conventional inorganic and flow chemistry for synthesis, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel platinum(IV) complexes will be synthesised using both conventional and Flow chemistry and characterised using a combination of 1H and 195Pt nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional 1H / 195Pt heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). The biological activity of the synthesised complexes will be undertaken with the assessment of cellular cytotoxicity and interactions with DNA. Ethics Application Requirements: None required Key References: 1. Metal Complexes and Therapeutic uses thereof, Fenton, R.R. and Aldrich-Wright, J.R. International Patent, Application Number PCT/AU02/00167, Oct., 2002 2. Fisher, D. M.; Bedarski, P. J.; Grunert, R.; Turner, P.; Fenton, R. R.; Aldrich-Wright, J. R. Chiral platinum(II) metallointercalators with potent in vitro cytotoxicity activity, ChemMedChem (2007), 2, 488-495. 3. Brodie, C.; Collins, J.G.; Aldrich-Wright, J.R. The biological activity of some square-planar platinum(II) metallointercalators. Journal of the Chemical Society, Dalton Transactions (2004), 1145-1152. 4. Krause-Heuer, A. M.; Grünert, Kühne, R. S.; Buczkowska, M.; Wheate, N. J.; Le Pevelen, D.; Boag, L. R.; Fisher, D. M.; Kasparkova, J.; Malina, J.; Bednarski, P. J. Brabec, Patrick V.; Aldrich-Wright, J. R. (2009) Studies into the mechanism of action of platinum(II) complexes with potent cytotoxicity in human cancer cells. Journal of Medicinal Chemistry, 52, 5474-5484. 5. Talib, J.; Beck, J. L.; Urathamakul, T.; Nguyen, C. D.; Aldrich-Wright, J. R.; Mackay, J. P.; Ralph, S. F. (2009) A mass spectrometric investigation of the ability of metal complexes to modulate transcription factor activity. Chemical Communications, (37), 5546-5548. 6. Fisher, D. M.; Fenton, R. R.; Aldrich-Wright, J.R. In vivo studies of a platinum(II) metallointercalator. Chemical Communications, (2008), 43, 5613-5615. 7. Krause-Heuer, A. M.; Grant, M. P.; Orkey, N.; Aldrich-Wright, J. R. Drug delivery devices and targeting agents for platinum(II) anticancer complexes, Australian Journal of Chemistry. Invited paper (2008), 61, 675-681. 8. Al Otaibi, A., Gordon, C. P., Sakoff, J. A., and McCluskey, A., The influence of ionic liquids on the Knoevenagel condensation of 1H-pyrrole-2-carbaldehyde with phenyl acetonitriles – cytotoxic 3-substituted-(1H-pyrrol-2yl)acrylonitriles, RSC Adv., 2014, 4, 19806 – 19813. 9. Hizartzidis, L., Tarleton, M., Gordon, C. P, McCluskey, A. Chemoselective Flow Hydrogenation Approaches to Isoindole-7-carboxylic acids and 7-Oxa-Bicyclio[2.2.1]heptanes, RSC Adv., 2014, 4, 9709-9722. 10.Gordon, C. P.; Hizartzidis, L.; Tarleton, M.; Sakoff, J. A.; Gilbert, J.; Campbell, B. E.; Gasser, R. B.; McCluskey, A. Discovery of acrylonitrile-based small molecules active against Haemonchus contortus. MedChemComm 2014, 5, 159-164.Tarleton, M.; Young, K. A.; Unicomb, E.; McCluskey, S. N.; Robertson, M. J.; Gordon, C. P.; McCluskey, A. A flow chemistry approach to norcantharidin analogues. Lett. Drug Des. Discovery 2011, 8, 568-574. 82 Title of Project: Synthesis of agents to prevent the formation of biofilms (FOR Code/s): 030201 Bioinorganic Chemistry & 030401 Biologically Active Molecules Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Ming Wu Contact: [email protected] Co-supervisor: Christopher Gordon Contact: [email protected] Location of Project: Project Background: As bacterial infection rate soar and death toll climbs, there is an urgent need to develop new reliable antibacterial drugs that are effective against bacterial infection and biofilms, a community of bacteria with extraordinary resistance to almost every drug developed to date. This project builds upon previously results, where the antimicrobial potential of some copper(II) complexes of the general structure [Cu(L1)(L2)]2+ (where L1 is a substituted 1,10-phenanthroline ligand and L2 is a diamine ligand, examples left) against Staphyloccocus aureus proved to be particularly promising (shown below).1 Positive control Vancomycin Cu-56MESS CLSM images of biofilms that were untreated (left panel), treated for 2 hours with vancomycin at 100 g/mL (centre panel) or Cu-56MESS at 100 g/mL (right panel). Side views of the biofilms are shown on top and on the right of each panel.6 Aim of Study: To synthesise and characterise complexes with antibacterial activity and of particular interest is biofilm eradication. Methods: Uses molecular modelling for design, both conventional inorganic and flow chemistry for synthesis, UV and CD for characterisation and biophysical techniques for biological assessment. The complexes will be synthesised and characterised using a combination of UV, CD, elemental analysis and electrospray ionisation mass spectroscopy (ESIMS). The biological activity of the synthesised complexes will be undertaken with the assessment of antibacterial activity and determination of the impact on biofilms. Ethics Application Requirements: None Key References: 1. N. S. Ng, MSc Thesis, University of Western Sydney, 2012. 2. J. M. Andrews, J. Antimicrob. Chemother., 2001, 48, 5. 3. Krause-Heuer, A.M., Leverett, P., Bolhuis, A., and Aldrich-Wright, J.R. (2012). Aust J Chem 65, 860-873. 4. Ng, N.S., Leverett, P., Hibbs, D.E., Yang, Q., Bulanadi, J.C., Wu, M.J., and Aldrich-Wright, J.R. (2013). Dalton Transactions 42, 3196-3209. 5. Beeton, M.L. Aldrich-Wright, J.R. and Bolhus, A. Anti-biofilm activity of copper(II) complexes, Journal of Inorganic Biochemistry 140 (2014) 167–172 83 Title of Project: Designing and synthesising compounds that selectively bind to quadruplex DNA (FOR Code/s): 030201 Bioinorganic Chemistry & 030401 Biologically Active Molecules Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Steven Ralph Contact: [email protected] Co-supervisor: David Harman Contact: [email protected] Co-supervisor: Christopher Gordon Contact: [email protected] Location of Project: Campbelltown Project Background: The recent discovery that non-classical Gquadruplex DNA (QDNA) structures exist in vivo has opened a new avenue for anticancer research. The unique structural features of QDNA provide a novel target for chemotherapeutic drug design and synthesis of QDNA selective small molecules is a flourishing area of research. This project intended to contribute to the design of novel anticancer agents through the further development of terpyridineplatinum(II) complexes (where terpyridine = 2,2':6',2''-terpyridine, terpy) which have demonstrated QDNA binding affinity. Aim of Study: : A series of novel platinum compounds will be synthesised that interact with Q-DNA. Methods: Uses molecular modelling for design, both conventional inorganic and flow chemistry for synthesis, preparative HPLC, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, twodimensional 1H correlation spectroscopy (NOSY), 2D heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). Ethics Application Requirements: None required Key References: 4. Harper, B. W. J.; van Holst, M.; Aldrich-Wright, J. R. (2011) Platinum(II) Intercalating Complexes Based on 2,2':6',2''Terpyridine. In: Metallointercalators, Synthesis and Techniques to Probe Their Interactions with Biomolecules (J. Aldrich-Wright, Ed.), Springer. 1st Edition. 5. Garbutcheon-Singh, K.B.; Grant, M.P.; Harper, B.W.; Krause-Heuer, A. M.; Manohar, M.; Orkey, N. U.; Aldrich Wright, J. R. (2011) Transition Metal Based Anticancer Drugs. Current Topics in Medicinal Chemistry, Invited paper. 11(5), 521-542. 6. Harper B. W.; Krause-Heuer, A. M.; Grant, M.P.; Manohar, M.; Garbutcheon-Singh,K. B.; Aldrich-Wright, J. R. (2010) Advances in platinum chemotherapeutics. Chemistry-A European Journal, 16, 7064-7077. 84 Title of Project: Development of diagnostic radiopharmaceuticals (FOR Code/s): 030201 Bioinorganic Chemistry & 030401 Biologically Active Molecules Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Christopher Gordon Contact: [email protected] Co-supervisor: Ivan Greguric Contact: [email protected] Co-supervisor: Ben Fraser Contact: [email protected] Location of Project: Campbelltown/ANSTO Project Background: [18F]fluorodeoxyglucose or FDG – the world’s most commonly prescribed fluorine-18 radiopharmaceutical is used to diagnose many forms of cancer through positron emission tomography (PET) imaging (see LHS image). FDG is preferentially taken up in cancer cells and is utilised for initial cancer diagnosis and for monitoring treatment progression. Although numerous radioisotopes are available for Positron Emission Tomography (PET) medical imaging, fluorine-18 remains very popular due to favourable physical properties. These include low energy positron emission (0.202 MeV), excellent decay profile (97% β+ emission), advantageous half-life (110 mins) and similar steric and electronic properties to the hydroxyl group. Currently we are developing fluorine-18 radiopharmaceuticals as diagnostic imaging agents for Alzheimer’s disease (metal chelators) and depression (organic cation 3 transporter inhibitors). Student top-up scholarships – The Australian Institute of Nuclear Scientists and Engineers (ANISE): UWS students undertaking honours projects in collaboration with ANSTO are eligible to apply for an honours scholarship ($5000 stipend) from AINSE. http://www.ainse.edu.au/grad_students2/honours_scholarships Aim of Study: To synthesise and characterise [18F]Diagnostics PET imaging agents for Alzheimers’s disease or depression. Methods: Uses molecular modelling for design, radiochemistry and flow chemistry for synthesis, preparative HPLC, radio HPLC, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, twodimensional 1H correlation spectroscopy (NOSY), two-dimensional heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). Ethics Application Requirements: None required Key References: 1. Brookmeyer, R. (1998) American Journal of Public Health 88, 7 2. Ferri, C. P., Prince, M., et.al.(2005) Lancet 366, 2112-2117 3. Bush, A. I., and Tanzi, R. E. (2008) Neurotherapeutics 5, 421-432 4. Bush, A. I. (2008) Journal of Alzheimer's Disease 15, 223-240 5. Sacco, C., Skowronsky, R. A., Gade, S., Kenney, J. M., and Spuches, A. M. (2012) JBIC, J. Biol. Inorg. Chem. 17, 531541 6. Sanghamitra, N. J. M., Varghese, N., and Rao, C. N. R. (2010) Chem. Phys. Lett. 496, 104-108 7. Miller, P. W., Long, N. J., Vilar, R., and Gee, A. D. (2008) Angewandte Chemie International Edition 47, 8998-9033 8. Toyama, H. (1993) Radioisotopes 42, 365-376 9. Vasdev, N., Cao, P., van Oosten, E. M., et.al. (2012) MedChemComm 3, 1228-1230 10. Babudri, F., Cardone, A., Cioffi, C. T., Farinola, G. M., Naso, F., and Ragni, R. (2006) Synthesis 2006, 1325-1332 11. Helin, A. F., and Vanderwerf, C. A. (1952) The Journal of Organic Chemistry 17, 229-232 12. Adlard, P. A., Cherny, R. A., et.al and Bush, A. I. (2008) Neuron 59, 43-55 13. Barnham, K. J., Kenche, V. B., et.al. (2008) Proceedings of the National Academy of Sciences 105, 6813-6818 14. Engel, Y., Dahan, A., Rozenshine-Kemelmakher, E., and Gozin, M. (2007) The Journal of Organic Chemistry 72, 2318-2328 15. Ross, T. L., Ermert, J., Hocke, C., and Coenen, H. H. (2007) Journal of the American Chemical Society 129, 80188025 16. Cai, L., Lu, S., and Pike, V. W. (2008) European Journal of Organic Chemistry 2008, 2853-2873 17. Olah, G. A., Chambers, R. D., and Prakash, G. K. S. (1992) Synthetic Fluorine Chemistry, John Wiley & Sons Inc 18. Wester, H. J. (2010) Pharmaceutical Radiochemistry (I), Scintomics, Furstenfeldbruck 85 Title of Project: Developing New Radio-metal PET Tracers: Ligands for Oxophillic Radio-metals (FOR Code/s): Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Ivan Greguric Contact: [email protected] Co-supervisor: Nigel Lengkeek Contact: [email protected] Co-supervisor: Ben Fraser Contact: [email protected] Campus/s project is offered and conducted: ANSTO Project Background: Zirconium-89 (89Zr) is a positron emitting radionuclide well suited to Positron Emission Tomography (PET) molecular imaging studies. Its long physical half-life, 78.4 hrs, makes it uniquely suited to imaging with molecules that have long biological half-lives and localisation times, the key example being monoclonal antibodies, so called 89Zr-Immuno-PET. There has been tremendous growth in the area of ‘biologicals’ for treatment of human disease, particularly cancer. The bacterial iron siderophore, desferrioxamine B (DFO), a trishydroxamate ligand is the most promising ligand for 89Zr and it is easily incorporated onto biomolecules (shown left). Radiolabelling of DFOfunctionalised antibodies with 89Zr is rapid and efficient with the radiolabelled biomolecules being largely stable in-vivo. However, there are a growing number of cases that show significant bone uptake. This is undesirable as it can lead to radiation to the sensitive bone marrow. To combat this problem we are developing a series of tetrahydroxamate ligands (an example is shown below) to tie up the two remaining coordination sites of Zr where other ligands can displace the DFO. This will hopefully improve their in-vivo stability. The ligands will be suitable for a range of emerging PET radioisotopes including 45Ti (t1/2 = 3.08 hr), 44Sc (t1/2 = 3.93 hr), 90Nb (t1/2 = 14.6 hr) and 89Zr (t1/2 = 78.4 hr). Student top-up scholarships – The Australian Institute of Nuclear Scientists and Engineers (ANISE): UWS students undertaking honours projects in collaboration with ANSTO are eligible to apply for an honours scholarship ($5000 stipend) from AINSE. http://www.ainse.edu.au/grad_students2/honours_scholarships Aim of Study: To synthesise and characterise tetrahydroxamate ligands for Zr89 complexation and antibody radiolabelling. Methods: Uses inorganic and synthetic chemistry for preparation of new ligands and ‘cold’ metal complexes; radiochemistry for the optimisation of radiolabelling procedures and biological labelling; Prep-HPLC, radio-HPLC, radio-TLC, NMR, UV-Vis, ESI-MS, LC-MS-MS, pH auto-titrations for characterisation; molecular modelling for design of ligands and biophysical techniques for the assessment of radiolabelled biological molecules. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, 2D 1H correlation spectroscopy (NOSY), two-dimensional heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). Ethics Application Requirements: None required Key References: 1. Bergeron, R.J.,. Chem. Rev., 1984. 84: p. 587 - 602. 2. Butler, A. and R.M. Theisen, Coord. Chem. Rev., 2010. 254: p. 288 - 296. 3. Hider, R.C. and X. Kong, Nat. Prod. Rep., 2010. 27: p. 637 - 657. 4. Raymond, K.N., G. Muller, and B.F. Matzanke, Top. Curr. Chem., 1984. 123: p. 50 - 101. 5. Deri, M.A., et al., Nuclear Medicine and Biology, 2013. 40(1): p. 3-14. 6. Zalutsky, M.R., Clinical Cancer Research, 2006. 12(7): p. 1958-1960. 7. Vugts, D.J. and G.A.M.S. van Dongen, Drug Discovery Today: Technologies, 2011. 8(2–4): p. e53-e61. 8. Wright, B.D. and S.E. Lapi, Journal of Nuclear Medicine, 2013. 54(8): p. 1171-1174. 86 Title of Project: Characterizing polysaccharides for a better health (FOR Code/s): Medicinal and Biomolecular Chemistry - Characterisation of biological macromolecules (030403) Macromolecular and Materials Chemistry - Physical Chemistry of Materials (030304) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Prof. Kelvin Chan Email: [email protected] Location of Project: Parramatta Project Background Polysaccharides are a major and key component of our diet (starch typically represents 50 % of our energy). Glucomannan is a polysaccharide obtained from Konjac and popular to prepare for example jellies in different Asian countries.[1] Glucomannans have health benefits, as dietary fibers, against for example type II diabetes and obesity. However, the reasons for these benefits are not known at the molecular level. It is thus necessary to characterize glucomannans at the molecular level. Galactomannnans are used as viscosifier in the food industry and other fields. They have similarities in chemical composition to the glucomannans: their characterisation is more advanced but tedious, time-consuming and still plagued by a number of uncertainties.[2] The molecular structure of complex polysaccharides and their molecular motion can be understood through the characterisation by solid-state NMR [3]. Solid-state NMR will be applied to the glucomannans and galactomannans: this characterization is possible without any modification of the sample (no dissolution or any type of modification is necessary). We also have recently showed that (free-solution) capillary electrophoresis can separate polysaccharides according to their composition [4]: the method is new, easy, fast and is applied for the first time to glucomannans and galactomannans. Aim of Study: To characterize ‘real’ glucomannans and galactomannans samples developing new capillary electrophoresis and NMR spectroscopy methods, for applications as healthier food. Methods: Solid-state NMR spectroscopy, Capillary electrophoresis. Ethics Application Requirements: Not applicable Key References: [1] M Chua, K Chan, TJ Hocking, PA Williams, CJ Perry, TC Baldwin, Methodologies for the extraction and analysis of konjac glucomannan from corms of Amorphophallus konjac K. Koch. Carbohydrate Polymers, 2012, 87, 22022210 [2] MA Pollard, R Kelly, PA Fischer, EJ Windhab, B Eder, R Amado, Investigation of molecular weight distribution of LBG galactomannan for flours prepared from individual seeds, mixtures, and commercial samples. Food Hydrocolloids 2008, 22, 1596-1606 [3] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386 [4] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 87 Field of Research: Title of Project: 0204 0299 0304 Consequences of chronic neuroinflammation on the brain: implications on Alzheimer's disease Supervisor: Prof Gerald Muench Email: [email protected] Telephone: 4620 3216 Co-supervisor: Dr Erika Gyengesi Email: [email protected] Telephone: 4620 3723 Dr Tim-Stait-Gardner [email protected] 4620 3216 Prof William S Price [email protected] 4620 3336 Campus project is offered and conducted: Campbelltown Background (max 500 words) Epidemiological evidence shows that plant-derived foods with anti-inflammatory and anti-oxidant potential protect against Alzheimer’s disease (AD), but it is not clear which compounds are responsible for this positive effect. Activated, cytokine-overexpressing microglia are near-universal components of Aβ plaques at early and mid-stages during the progression of AD, and only decline in end-stage, dense core plaques. Activated microglia show close associations with tangle-bearing cholinergic neurons in AD. However, transgenic animal models of AD, which overexpressing mutant forms of presenilin, tau and amyloid precursor protein do not show the same variety of pro-inflammatory markers as human AD patients and develop a much weaker neuroinflammatory phenotype. To establish an animal model in which specific food compounds can be tested, we will use transgenic mice, which show chronic brain inflammation and develop progressive neurological deficits. We will monitor changes in their behavior, including a decline in cognitive functions. We will also investigate the underlying pathological changes, e.g. how chronic inflammation destroys nerve cells and their connections by using anatomical methods and MRI scans. Finally, we will investigate to what degree curcumin, a natural anti-oxidant and anti-inflammatory compound, can attenuate inflammation, prevent brain damage, and the loss of memory functions in our mice. We expect that our model will assist in the selection of potent candidate drugs, which can then be validated in clinical trials with Alzheimer patients. Aim of Study: The specific aims of this study are: 1. To study the effects of chronic neuroinflammation on the deterioration of memory and cognition in the GFAP-IL-6 overexpressing mice during their lifespan. The changes of the brain structure will be also examined by high resolution Magnetic Resonance Imaging (MRI). 2. To study the effects of neuroinflammation on the morphological structure of the basal forebrain cholinergic system and the interconnected areas using immunohistochemistry. 3. To investigate the effects of a high bioavailable preparation of the anti-inflammatory compound curcumin on brain inflammation, neurodegeneration and cognitive decline. Methods: Specific aim 1. To study the effects of chronic neuroinflammation on the deterioration of memory and cognition in the IL-6 overexpressing mice during their lifespan. Specific aim 2. To study the effects of neuroinflammation on the morphological structure of the basal forebrain cholinergic system and its interconnected areas. Specific aim 3. To investigate the effects of anti-inflammatory compound curcumin on brain inflammation, neurodegeneration and synaptic decline. Ethics Application Requirements: Animal Research Authority application has been approved by the UWS Animal Ethics committee to conduct animal research, as documented in Animal Research and Teaching Proposal Number: A10057; Title: Anatomical and behavioural studies of the rodent brain during neuroinflammation in IL6-GFAP mice; at the following site: Animal holdings - C Building 30 SoM animal holdings 88 Key References: 31. Ikegami, S. Behavioral impairment in radial-arm maze learning and acetylcholine content of the hippocampus and cerebral cortex in aged mice. Behav Brain Res 65, 103-111 (1994). 32. Heyser, C. J., Masliah, E., Samimi, A., Campbell, I. L. & Gold, L. H. Progressive decline in avoidance learning paralleled by inflammatory neurodegeneration in transgenic mice expressing interleukin 6 in the brain. Proc Natl Acad Sci U S A 94, 1500-1505 (1997). 33. Campbell, I. L. et al. Transgenic models to assess the pathogenic actions of cytokines in the central nervous system. Mol Psychiatry 2, 125-129 (1997). 34. Campbell, I. L. & Powell, H. C. Role of Cytokines in Demyelinating Disease Studied in Transgenic Mice. Methods 10, 462-477 (1996). 35. Campbell, I. L., Kay, T. W., Oxbrow, L. & Harrison, L. C. Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. J Clin Invest 87, 739-742, doi:10.1172/JCI115055 (1991). 36. Campbell, I. L., Eddleston, M., Kemper, P., Oldstone, M. B. & Hobbs, M. V. Activation of cerebral cytokine gene expression and its correlation with onset of reactive astrocyte and acute-phase response gene expression in scrapie. J Virol 68, 2383-2387 (1994). 37. Campbell, I. L. & Chiang, C. S. Cytokine involvement in central nervous system disease. Implications from transgenic mice. Ann N Y Acad Sci 771, 301-312 (1995). 38. Campbell, I. L. et al. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci U S A 90, 10061-10065 (1993). 39. Campbell, I. L. Structural and functional impact of the transgenic expression of cytokines in the CNS. Ann N Y Acad Sci 840, 83-96 (1998). 40. Fuller, S., Munch, G. & Steele, M. Activated astrocytes: a therapeutic target in Alzheimer's disease? Expert Rev Neurother 9, 1585-1594, doi:10.1586/ern.09.111 (2009). 41. Maczurek, A., Shanmugam, K. & Munch, G. Inflammation and the redox-sensitive AGE-RAGE pathway as a therapeutic target in Alzheimer's disease. Ann N Y Acad Sci 1126, 147-151, doi:10.1196/annals.1433.026 (2008). 42. Steele, M., Stuchbury, G. & Munch, G. The molecular basis of the prevention of Alzheimer's disease through healthy nutrition. Exp Gerontol 42, 28-36, doi:10.1016/j.exger.2006.06.002 (2007). 43. Huber, A., Stuchbury, G., Burkle, A., Burnell, J. & Munch, G. Neuroprotective therapies for Alzheimer's disease. Curr Pharm Des 12, 705-717 (2006). 44. Stuchbury, G. & Munch, G. Alzheimer's associated inflammation, potential drug targets and future therapies. J Neural Transm 112, 429-453, doi:10.1007/s00702-004-0188-x (2005). 45. Munch, G. et al. Microglial activation induces cell death, inhibits neurite outgrowth and causes neurite retraction of differentiated neuroblastoma cells. Exp Brain Res 150, 1-8, doi:10.1007/s00221-003-1389-5 (2003). 89 Field of Research: Title of Project: 0204 0303 0304 0306 Expanding the Boundaries and Applications of Diffusion NMR Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Allan Torres Email: [email protected] Telephone: 4620 3459 Campus project is offered and conducted: Campbelltown Background (max 500 words) Diffusion NMR is routinely used to study various molecular properties, and interactions occurring in solution. This technique is also valuable in MRI as it can be used to probe microscopic structures in biological tissues. Recently, longlived singlet spin states have been used in NMR diffusion and diffusion-diffraction studies. Unlike regular spin coherences, singlet spin states have significantly longer lifetimes on the order of tens of seconds to a minute making it feasible to study extremely slowly diffusing molecules. In diffusion-diffraction studies, long lived singlet states can potentially be useful for probing structures with larger characteristic distances. In this project, the restricted diffusion of test molecules in glass and flexible silica capillaries will be investigated by utilising singlet spin states and various NMR coherences. The feasibility of performing NMR diffusion experiments in a single capillary with internal diameter of 10-200 micrometers will also be studied. (Would suit students interested in NMR/Physical Chemistry/Physics) Aim of Study: To characterise NMR diffusion in capillaries using various spin coherences and singlet spin states. Methods: Nuclear Magnetic Resonance Spectroscopy Ethics Application Requirements: Not Applicable Key References: 9. M. Carravetta and M.H. Levitt, Long-lived nuclear spin states in high-field solution NMR. J. Am. Chem. Soc. 126 (2004) 6228-6229. 10. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 11. N.N. Yadav, A.M. Torres and W.S. Price, NMR q-space imaging of macroscopic pores using singlet spin states. J. Magn. Reson. 204 (2010) 346-348. 12. A.M. Torres, B. Ghadirian and W.S. Price, Diffusion-diffraction using singlet spin states and various NMR coherences in a J-coupled AX spin system. RSC Advances 8 (2012) 3352-3360. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 90 Field of Research: Title of Project: 0204 0299 0304 0306 Investigating Biostructures using NMR/MRI Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Tim-Stait-Gardner Email: [email protected] Telephone: 4620 3114 Campus project is offered and conducted: Campbelltown Background (max 500 words) Biological tissue is not just an amorphous arrangement of cells. Indeed most tissue has an underlying structure composed of microscopic components as in muscle fibres or, as has more recently been realised, fibre tracts in brain tissue. Although the tracts might ultimately be macroscopic, they are composed of microscopic components. Such structures are not only involved in normal biological function, but also in diseased states, such as multiple sclerosis, epilepsy, and Alzheimer’s disease. Traditional techniques used to visualise such structures are not only limited in their application, but often these methods are invasive and tedious. In this project new NMR/MRI diffusion methods will be used to characterise tissue microstructure on a microscopic scale well below the resolution that is achievable using standard MRI sequences. In addition, the student would participate in the development of new NMR/MRI methods aimed at elucidating sample microstructure. (Would suit students interested in Biology/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To characterise a variety of tissue microstructures (mainly brain and muscle) and to participate in the development of new NMR techniques with this purpose. Methods: Nuclear Magnetic Resonance Spectroscopy and Imaging Ethics Application Requirements: May be necessary for some tissue samples. Key References: 7. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 8. S. Mori, J. Zhang, Principles of diffusion tensor imaging and its applications to basic neuroscience research, Neuron 51 (2006) 527-539. 9. P. Callaghan, Principles of Nuclear Magnetic Resonance Microscopy, Oxford University Press 1994. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 91 Field of Research: Title of Project: 0204 0303 0304 0306 Quantitative Composition-Flavour Relationships Supervisor: Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Co-supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Campus project is offered and conducted: Campbelltown Background (max 500 words) Have you ever thought about why different wines have different tastes? What is controlling the flavour? What chemicals contribute to the flavour generation process? Are these chemicals staying as monomers or forming assemblies in the wine? The results of this study will answer all these tricky questions. (Would suit students interested in Biology/Chemistry/NMR/Physics/Statistics/Wine tasting) Aim of Study: To build an NMR-based wine tasting machine Methods: Nuclear Magnetic Resonance Spectroscopy Pattern Recognition Ethics Application Requirements: Not Applicable Key References: 3. Hu, N., D. Wu, K. Cross, S. Burikov, T. Dolenko, S. Patsaeva, and D.W. Schaefer, Structurability: A collective measure of the structural differences in vodkas. Journal of Agricultural and Food Chemistry, 2010. 58(12): p. 73947401. 4. Polášková, P., J. Herszage, and S.E. Ebeler, Wine flavor: Chemistry in a glass. Chemical Society Reviews, 2008. 37(11): p. 2478-2489. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 92 Field of Research: Title of Project: 0204 0303 0304 0306 Studying Ice Nucleation Protein Motifs with NMR Diffusion Measurements Supervisor: Prof. William S. Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Scott A Willis Email: [email protected] Telephone: 4620 3114 Dr Allan Torres [email protected] 4620 3459 Dr Gang Zheng [email protected] 4620 3729 Campus project is offered and conducted: Campbelltown Background (max 500 words) Freeze tolerance is important for life that exists in low temperature environments. Protection strategies include the use of antifreeze proteins to prevent ice crystal growth or the use of ice nucleation proteins (INPs).1, 2 INPs initiate ice formation earlier so that the organism has a chance to respond to the freezing for thermal protection or could be used as a means of retrieving nutrients from plants.1 INPs are thought to bind to water molecules in a way that resembles an ice crystal3 such that further nucleation is promoted but the mechanism is not fully understood. As such a study of translational diffusion4 and hydration of these proteins in aqueous solutions at various temperatures is pertinent for understanding this and would be of interest for potential applications of these proteins. (Would suit students interested in Biology/Chemistry/NMR) Aim of Study: This project aims to investigate particular motifs common in INPs via NMR diffusion methods at various temperatures to determine if they are useful for ice nucleation. Methods: NMR Diffusion Experiments + Analysis Ethics Application Requirements: Not Applicable Key References: 8. Zachariassen, K. E., Kristiansen, E., Cryobiology, 2000, 41, 257 – 279. 9. Graether, S. P., Jia, Z., Biophysical Journal, 2001, 80, 1169 – 1173. 10. Green, R. L., Warren, G. L., Nature, 1985, 317, 645 – 648. 11. Price, W. S., NMR Studies of Translational Motion. Cambridge University Press: New York, 2009. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 93 Physical Chemistry (incl Structural) 94 Title of Project: The design, synthesis and characterisation of platinum(IV) prodrugs using flow chemistry (FOR Code/s): 030302 Nanochemistry and Supramolecular Chemistry & 030605 Solution Chemistry Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Chris Gordon Contact: [email protected] Co-supervisor: Gang Zheng Contact: [email protected] Location of Project: Campbelltown Project Background: Platinum(II) compounds which X2 OAc X2 OH H2 H2 have exceptional anticancer activity have been N N N N * Pt * developed at UWS and form the basis of an Pt * N * N N N international patent. Some compounds have been H2 H2 OAc OH synthesised and insights gained from the structureactivity relationships which have allowed us to make X2 OAc X2 HO modifications to the structure that have resulted in a H2 H2 N N N N steady improvement in anticancer activity, (assessed * * Pt Pt * by in vitro cytotoxicity assay against the L1210 murine * N N N N H2 H2 leukaemia cell line). For example, substitution at the 5 OH OAc or 5, 6 positions of the intercalator, 1,10phenathroline (phen) produces compounds with increased activity. Moreover, when a chiral ancillary ligand, such as 1S,2S-diaminocyclohexane is included a further increase in activity is produced. Aim of Study: To synthesise and characterise novel platinum(IV) complexes using both conventional and flow chemistry. The anticancer activity of the resulting complexes will be assessed as a prelude to their application as prodrugs. Methods: Uses molecular modelling for design, both conventional inorganic and flow chemistry for synthesis, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel platinum(IV) complexes will be synthesised using both conventional and Flow chemistry and characterised using a combination of 1H and 195Pt nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional 1H / 195Pt heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). The biological activity of the synthesised complexes will be undertaken with the assessment of cellular cytotoxicity and interactions with DNA. Ethics Application Requirements: None required Key References: 1. Metal Complexes and Therapeutic uses thereof, Fenton, R.R. and Aldrich-Wright, J.R. International Patent, Application Number PCT/AU02/00167, Oct., 2002 2. Fisher, D. M.; Bedarski, P. J.; Grunert, R.; Turner, P.; Fenton, R. R.; Aldrich-Wright, J. R. Chiral platinum(II) metallointercalators with potent in vitro cytotoxicity activity, ChemMedChem (2007), 2, 488-495. 3. Brodie, C.; Collins, J.G.; Aldrich-Wright, J.R. The biological activity of some square-planar platinum(II) metallointercalators. Journal of the Chemical Society, Dalton Transactions (2004), 1145-1152. 4. Krause-Heuer, A. M.; Grünert, Kühne, R. S.; Buczkowska, M.; Wheate, N. J.; Le Pevelen, D.; Boag, L. R.; Fisher, D. M.; Kasparkova, J.; Malina, J.; Bednarski, P. J. Brabec, Patrick V.; Aldrich-Wright, J. R. (2009) Studies into the mechanism of action of platinum(II) complexes with potent cytotoxicity in human cancer cells. Journal of Medicinal Chemistry, 52, 5474-5484. 5. Talib, J.; Beck, J. L.; Urathamakul, T.; Nguyen, C. D.; Aldrich-Wright, J. R.; Mackay, J. P.; Ralph, S. F. (2009) A mass spectrometric investigation of the ability of metal complexes to modulate transcription factor activity. Chemical Communications, (37), 5546-5548. 6. Fisher, D. M.; Fenton, R. R.; Aldrich-Wright, J.R. In vivo studies of a platinum(II) metallointercalator. Chemical Communications, (2008), 43, 5613-5615. 7. Krause-Heuer, A. M.; Grant, M. P.; Orkey, N.; Aldrich-Wright, J. R. Drug delivery devices and targeting agents for platinum(II) anticancer complexes, Australian Journal of Chemistry. Invited paper (2008), 61, 675-681 95 Title of Project: Synthesising N4-tetradentates for coordination to transition metals (FOR Code/s): 030302 Nanochemistry and Supramolecular Chemistry & 030605 Solution Chemistry Supervisor: Janice Aldrich-Wright Contact: [email protected] Co-supervisor: Chris Gordon Contact: [email protected] Co-supervisor: Allan Torres Contact: [email protected] Location of Project: Campbelltown Project Background: There are three stereochemical types of continuous chain N4tetradentates: planar, non-planar and facultative. Because of their structural inflexibility, planar N4-tetradentates, coordinate all four donor atoms to the metal in the same plane. Nonplanar N4-tetradentates coordinate the four donor atoms tetrahedrally about a metal atom. Facultative N4-tetradentates can coordinate all four donor atoms in either a planar or nonplanar arrangement because of their structural flexibility. The coordination chemistry of facultative ligands, like triethylenetetramine (trien), can offer a considerable range of stereisomers by arranging their donor atoms around a metal atom in several of ways. The factor which may determine the disposition may be considered, they comprise of E-strain which includes all forces defining the conformation of the chelate rings. B-strain refers to steric effects as substituents are added to the individual chelate rings will cause restrictions on the neighbouring chelate rings. C-strain is due to the incompatibility of the positioning of the donor atoms of a ligand. A balanced combination of these three effects determines the topology adopted by a N4-tetradentate ligand on coordination and consequently the stability of the complex. N4-Tetradentates ligands offer unique structural properties and upon coordination to metals symmetrical cis-α and unsymmetrical cis-β-positions (shown in the figure) can form. Aim of Study: To synthesise and characterise N4-tetradentate ligands and subsequently coordinate them metals, such as ruthenium cobalt or platinum(II) and (IV) using both conventional and flow chemistry, before their biological activity is determined. Methods: Uses, molecular modelling for design, both conventional inorganic and flow chemistry for synthesis, NMR, UV and CD for characterisation and biophysical techniques for biological assessment. Novel complexes will be synthesised and characterised using a combination of 1H nuclear magnetic resonance, two-dimensional 1H correlation spectroscopy (NOSY), two-dimensional heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectroscopy (ESI-MS). The biological activity of the synthesised complexes will be undertaken with the assessment of cellular cytotoxicity and interactions with DNA. Ethics Application Requirements: None required Key References: 1. Aldrich-Wright, J. R.; Fenton, R. F.; Greguric, I. D.; Hambley, T. W.; Williams, P. A. The stereospecific synthesis of α-{dipyrido[3,2-a:2'3'-c](6,7,8,9-tetrahydro)phenazine [N,N'-di(2-picolyl)-2,5-dimethyl-2S,5S-diaminocyclohexane] ruthenium(II)} and related β -isomers. Dalton Transactions, (2002), 4666-4671. 2. Aldrich-Wright, J.; Vagg, R. S.; Williams, P. A. Design of chiral picen-based metal complexes for molecular recognition of α- aminoacids and nucleic acids, Coordination Chemistry Reviews (1997), 166, 361-389. 3. Cross, R.J., Farrugia, L.J., Newman, P.D., Peacock, R.D., and Stirling, D. Metal Complexes of New, Chiral N2O2 Tetradentate Ligands. Inorganic Chemistry (1999). 38, 1186-1192. 96 Title of Project: Towards high quality bioplastics (FOR Code/s): Macromolecular and Materials Chemistry – Synthesis of Materials (030306) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Aurelia Charlot Email: [email protected] Location of Project: Parramatta Project Background It is desirable to replace materials derived from oil, such as current plastics, by new ones derived from renewable resources such as cellulose or galactomannans. Cellulose is a significant waste from agriculture, while galactomannans like guar gums are an additive used in the food industry whose resources are largely under-used [1,2]. This is due to the poor intrinsic mechanical properties of these polysaccharides as well as their high sensitivity to moisture. These polysaccharides are often chemically modified to adjust performance to the level of current plastics. Polysaccharides consist of molecules with different types of saccharide units (glucose, galactose, mannose), different molecular weights and different topologies: linear chains or branched ones. The chemical modification improves the properties but also adds to the complexity of the molecules. The elucidation of their structure is needed for the scientific design of bioplastics. We collaborate with Dr Aurelia Charlot and Prof Etienne Fleury (INSA, Lyon, France) to answer these fundamental questions. This project has a strong potential to lead to industrial collaborations. Aim of Study: To characterise and assess potential bioplastics derived from cellulose or galactomannans. With solidstate NMR [3] we will reveal the interplay between molecular structure and molecular motions, and explore the crucial role of moisture. We will use capillary electrophoresis (in the critical conditions) [4] to separate compounds with different compositions and different degrees of modification. Methods: Capillary electrophoresis, Solid-state NMR spectroscopy. Ethics Application Requirements: Not applicable Key References: [1] C Lacroix, E Sultan, E Fleury, A Charlot, Functional galactomannan platform from convenient esterification in imidazolium-based ionic liquids. Polymer Chemistry 2012, 3, 538-46 [2] G Mangiante, P Alcouffe, B Burdin, M Gaborieau, E Zeno, M Petit-Conil, J Bernard, A Charlot, E Fleury, Green nondegrading approach to alkyne-functionalized cellulose fibers and biohybrids thereof: synthesis and mapping of the derivatization. Biomacromolecules 2013, 14, 254-63 [3] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386 [4] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 97 Title of Project: Polysaccharide-water interactions by solid-state NMR (FOR Code/s): Physical chemistry – Structure Chemistry and Spectroscopy (030606) Macromolecular and Materials Chemistry - Physical Chemistry of Materials (030304) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Robert Graf Email: [email protected] Location of Project: Parramatta Project Background Starch is the main source of energy in human diet, as it is a major component of wheat, maize, potatoes and rice. It is renewable, cheap and biodegradable, and therefore has major applications in the paper, pharmaceutical and textile industries. Starch is a chemically simple polymer (a homopolymer of glucose) but it has a very complex macromolecular (branched) and supramolecular structure, with six identified hierarchical levels, on scales ranging from nm to mm. Its hydrogen-bonding capacity, provided by three hydroxyl groups per glucose unit, is crucial for its solid-state structure as well as its behaviour in solution. Starch granules contain water molecules, which are an integral part of the semi-crystalline structure. Starch-water interactions play an important role in the mechanical properties of starch-based bioplastics. They also define the first stages of cooking of starch, and therefore are expected to play a role in diet-related diseases such as obesity and diabetes. Solid-state Nuclear Magnetic Resonance (NMR) is an invaluable tool in the study of polymer materials such as polysaccharides: it yields local information on their structure and dynamics [1,2]. This project will build on the expertise of Dr Marion Gaborieau in solid-state nuclear magnetic resonance (NMR) of native and functionalized polysaccharides. Aim of Study: In this study, the local dynamics of starch and residual water will be investigated on the molecular level as a function of sample temperature by solid-state nuclear magnetic resonance (NMR) methods. The study will also be extended to other polysaccharides and real food such as breakfast cereals and rice. This will shed light onto hydrogen bonding capacity of starch (as a model polysaccharide) and its interactions with water. It will help elucidate the poorly-understood endothermic transition observed by differential scanning calorimetry for many polysaccharides [3]. Methods: Solid-state NMR spectroscopy, differential scanning calorimetry (DSC). Ethics Application Requirements: Not applicable Key References: [1] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386 [2] G Mangiante, P Alcouffe, B Burdin, M Gaborieau, E Zeno, M Petit-Conil, J Bernard, A Charlot, E Fleury, Green nondegrading approach to alkyne-functionalized cellulose fibers and biohybrids thereof: synthesis and mapping of the derivatization. Biomacromolecules 2013, 14, 254-263 [3] IAM Appelqvist, D Cooke, MJ Gidley, SJ Lane, Thermal properties of polysaccharides at low moisture: An endothermic melting process and water-carbohydrate interactions. Carbohydrate Polymers 1993, 20, 291-299 98 Title of Project: Effect of temperature on branching in rice starch (FOR Code/s): Agriculture - Crop & Pasture Improvement (Selection and Breeding) (070305) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Rachelle Ward Email: [email protected] Co-supervisor: Dr Laura Pallas Email: [email protected] Location of Project: Parramatta Project Background The amount of amylose and the nature of its branching are influenced by night temperatures [1]. This degree of branching has been shown to directly impact the cooking quality and texture of the rice grain. The Waxy gene has been linked to changes in amylose although this does not explain all observed changes in amylose. One hypothesis to explain the amylose structure is the changed activity of starch branching enzymes, however these environmental influences, in combination with genetic differences in the waxy and starch branching enzyme genes have not been studied in the Australian rice germplasm. This investigation will analyse 12 parental lines of rice (Oryza sativa) from the rice breeding program at the Yanco Agricultural Institute. These lines comprise three variations of interest in the waxy gene, high amylose and low amylose contents (identifiable by 3 SNPs within the Waxy gene) along with two possible combinations of Starch Branching Enzymes. The 12 plants will be grown in replicates of 12 in a glasshouse until flowering where half will be moved to a higher temperature glasshouse and the other half to a control/normal temperature. Upon harvesting the amylose from the grain will be measured, then extracted by use of hot water and the starch structure will be analysed by capillary electrophoresis and NMR. Aim of Study: To measure degrees of branching using NMR spectroscopy [2], as well as amylopectin-to-amylose ratio and amylose chain lengths using capillary electrophoresis to identify the effect of night time temperatures on the activity starch branching enzyme. Methods: Capillary electrophoresis, NMR spectroscopy. Ethics Application Requirements: Not applicable Key References: [1] PA Counce, RJ Bryant, CJ Bergman, RC Bautista, YJ Wang, TJ Siebenmorgen, KAK Molenhauer, JFC Meullenet, Rice milling quality, grain dimensions, and starch branching as affected by high night temperatures. AACC International, 2005, 82(6), 645-648 [2] M Gaborieau, H DeBruyn, S Mange, P Castignolles, A Brockmeyer, RG Gilbert, Synthesis and characterization of synthetic polymer colloids colloidally stabilized by cationized starch oligomers. Journal of Polymer Science Part A Polymer Chemistry, 2009, 47, 1836-1852 99 Title of Project: New methods to characterise breakfast cereals (FOR Code/s): Analytical Chemistry – Separation Science (030108) Food Sciences - Food Chemistry and Molecular Gastronomy (excl. Wine) (090801) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Ashok Shrestha Email: [email protected] Telephone: 1296 Location of Project: Parramatta Project Background Breakfast cereals are nutrient-dense processed foods and are expected to have several health benefits. They are expected to have a low glycemic index (low GI, which means that they are digested slowly [1]). Most of them are also externally fortified with folic acid (Pteroylglutamic acid) to prevent the incidence of neural tube defects [2]. Their analysis is complicated by the fact that they are only partially soluble in water [3]. Traditional methods of folic acid analysis such as HPLC, or microbiological assay are tedious and time consuming. Our preliminary results showed that capillary electrophoresis is a fast method to detect folic acid. It is also an excellent tool of the separation and detection of sugars [4,5]. Aim of Study: The aim of the project is to develop new methods for a faster, more accurate, and robust characterisation of cereal-based foods, based on free-solution capillary electrophoresis. Folates and sugars will be quantified. These methods could be compared to the established, but tedious and expensive, HPLC methods. The full samples will also be characterised with solid-state NMR spectroscopy and ATR IR spectroscopy, thus avoiding dissolution artefacts. Methods: Capillary electrophoresis, NMR spectroscopy, ATR IR spectroscopy, high-performance liquid chromatography (HPLC). Ethics Application Requirements: Not applicable Key References: [1] AC Dona, G Pages, RG Gilbert, M Gaborieau, PW Kuchel, Kinetics of in vitro digestion of starches monitored by time-resolved 1H nuclear magnetic resonance. Biomacromolecules, 2009, 10, 638-644 [2] J Arcot, A Shrestha, Folate: methods of analysis. Trends in Food Science & Technology, 2005, 16, 253–266 [3] S Schmitz, AC Dona, P Castignolles, RG Gilbert, M Gaborieau, Assessment of the extent of starch dissolution in dimethylsulfoxide by 1H NMR spectroscopy. Macromolecular Bioscience 2009, 9, 506-514 [4] JD Oliver, M Gaborieau, EF Hilder, P Castignolles, Simple and robust determination of monosaccharides in plant fibers in complex mixtures by capillary electrophoresis and high performance liquid chromatography. Journal of Chromatography A, 2013, 1291, 179-186 [5] JD Oliver, AA Rosser, CM Fellows, Y Guillaneuf, JL Clement, M Gaborieau, P Castignolles, Understanding and improving direct UV detection of monosaccharides and disaccharides in free solution capillary electrophoresis. Analytica Chimica Acta 2014, 809, 183 100 Title of Project: Smart polymers as the additives of the future (FOR Code/s): Macromolecular and Materials Chemistry – Polymerisation mechanisms (030305) Analytical Chemistry - Separation Science (030108) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Prof Mathias Destarac Email: [email protected] Location of Project: Parramatta Project Background ’Smart’ polymeric materials react to changes in temperature or pH. These ‘smart’ polymers are intensively researched for use in drug delivery, water purification and more. The ‘smart’ behaviour of these materials is making their characterization difficult by common liquid chromatography methods. The team of Prof. Mathias Destarac (University Paul Sabatier, Toulouse, France) developed a new technology to synthesize some complex polymers in which part of the polymer chain is cationic, while the other part is neutral and thermoresponsive [1]. The cationic part ensures this polymer has great adhesive properties on a number of substrates. The thermoresponsive properties mean that the materials is water-soluble at low temperature but not at high temperature. Aim of Study: The characterization of these polymers has been extremely challenging up to now due to the presence of the charges. We propose to use this charge at our advantage and separate the polymers using an electric field, i.e. using capillary electrophoresis [2]. The self-assembly of these polymers leads to powerful and fascinating structures that could be characterized using solid-state NMR [3]. Methods: Capillary electrophoresis, solid-state NMR spectroscopy. Ethics Application Requirements: Not applicable Key References: [1] M Destarac, On the critical role of RAFT agent design in reversible addition-fragmentation chain transfer (RAFT) polymerization. Polymer Reviews 2011, 51, 163-187 [2] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 [3] W Gu, M Gaborieau, VT Huynh, PL de Souza, MH Stenzel, Functionalization of microspheres with malonates using Michael addition as a pathway to create a drug delivery system for platinum drugs for the treatment of liver cancer. Polymer 2011, 52, 5993-6002 101 Title of Project: Characterisation of functionalised chitosan films (for cell culture) (FOR Code/s): Physical Chemistry – Colloid and Surface chemistry (030603) Biochemistry and Cell Biology (0601) Macromolecular and Materials Chemistry - Physical Chemistry of Materials (030304) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Richard Wuhrer Email: [email protected] Telephone: 9089 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Location of Project: Parramatta Project Background Chitosan is an amazing polymer derived from chitin, the main component of crab or prawn shells and many others. On top of being a renewable and sustainable material, chitosan is bacteriostatic and it has thus a great potential to produce films for cells culture.[1] Our research group has developed a methodology to functionalise chitosan films with small biomolecules and quantify the grafting and these biomolecules. The surface of the film and its functionality are the key to avoid film-to-film variability in the cell culture. Scanning Electron Microscopy (SEM) allows probing the morphology of the film surface. The functionalization can be assessed through SIMS-ToF. A more in-depth analysis of the roughness is possible through Atomic Force Microscopy (AFM). All these powerful characterisation methods are available at UWS. Aim of Study: To characterise the roughness and functionalization of a chitosan film surface. Methods: SEM, SiMS ToF, AFM Ethics Application Requirements: Not applicable Key References: [1] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis and X-ray diffraction. Biomacromolecules 2011, 12, 1380. 102 Title of Project: Structure of polyamides and adhesive properties (FOR Code/s): Macromolecular and Materials Chemistry – Chemical characterisation of Materials (030301) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Richard Wuhrer Email: [email protected] Telephone: 9089 Location of Project: Parramatta Project Background Polyamides have been a very successful industrial story since their discovery in the 1930s by the company Dupont de Nemours. Nylon is likely the most well-known member of this family. The difficulties to characterise these polymers may have limited the expansion of this family. One key innovation has however been the use of fatty acids (from paper production for example) to produce polyamides for industrial adhesives (hot-melt adhesives). These polyamides come from a sustainable and renewable source, but they are then complex in terms of chemical structure, namely composition. We have shown that capillary electrophoresis (CE) is a simple and robust method to characterise the composition of complex polysaccharides.[1,2] This method will be applied to polyamide subjected to acid hydrolysis. The resulting samples will also be analysed with solution-state NMR spectroscopy. The hydrolysis should only lead to depolymerisation but other degradation processes may also take place. Adhesives, as most industrial materials, are loaded with a number of additives. To investigate potential degradation and the presence of additives, solid state characterisation methods will also be applied: solid-state NMR [3] and ATR IR spectroscopies. This project can lead to collaborations and job opportunities in various manufacturing companies. Aim of Study: To relate the chemical composition of hot meld adhesives to their adhesive properties. Methods: Capillary electrophoresis, solution-state and solid state NMR spectroscopies, ATR IR spectroscopy Ethics Application Requirements: Not applicable Key References: [1] JD Oliver, M Gaborieau, EF Hilder, P Castignolles, Simple and robust determination of monosaccharides in plant fibers in complex mixtures by capillary electrophoresis and high performance liquid chromatography. Journal of Chromatography A 2013, 1291, 179-186 [2] JJ Thevarajah, M Gaborieau, P Castignolles, Separation and characterization of synthetic polyelectrolytes and polysaccharides with capillary electrophoresis. Advances in Chemistry 2014, 2014, Article ID 798503 [3] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis and X-ray diffraction. Biomacromolecules 2011, 12, 1380-1386 103 Title of Project: What is a true solution (of chitosan)? Does it exist? And why does it matter? (FOR Code/s): Macromolecular and Materials Chemistry - Physical Chemistry of Materials (030304) Analytical Chemistry - Separation Science (030108) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Michael O’Connor Email: m.o'[email protected] Telephone: 3902 Location of Project: Mainly Parramatta, but also Campbelltown for cell culture Project Background Chitosan is an amazing polymer derived from chitin, the main component of crab or prawn shells and many others. On top of being a renewable and sustainable material, chitosan is bacteriostatic and it has thus a great potential to produce films for cell culture or transplantation and regenerative medicine.[1] Our research group has developed a methodology to functionalise chitosan films with small biomolecules and quantify the grafting and these biomolecules.[2] However, the homogeneity of the film surface currently needs to be improved. The films are obtained by casting a chitosan “solution” and evaporating the solvent. Preliminary investigations show that the heterogeneity of the chitosan film surface may arise from the presence of aggregates in the chitosan “solution”. Pressure mobilisation or capillary electrophoresis can give a quick assessment of the kinetics of dissolution of the chitosan available from different sources. This can be completed by time-resolved NMR spectroscopy [3] and then quantitative NMR spectroscopy [4]. Different methods to cast the films will also be investigated and compared. Cells will be cultured on these films to assess the homogeneity of the film surface as well as the film-to-film variability. By identifying ways of improving chitosan film production, this project will advance the fields of both polymer chemistry and regenerative medicine. Aim of Study: To obtain a true chitosan solution for reproducible casting of chitosan film with homogenous surfaces Methods: Capillary electrophoresis, NMR spectroscopy, Cell culture Ethics Application Requirements: Not applicable Key References: [1] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis and X-ray diffraction. Biomacromolecules 2011, 12, 1380 [2] C Lefay, Y Guillaneuf, G Moreira, JJ Thevarajah, P Castignolles, F Ziarelli, E Bloch, M Major, L Charles, M Gaborieau, D Bertin, D Gigmes, Heterogeneous modification of chitosan via nitroxide-mediated polymerization. Polymer Chemistry 2013, 4, 322 [3] A Dona, C-WW Yuen, J Peate, RG Gilbert, P Castignolles, M Gaborieau, A new NMR method for directly monitoring and quantifying the dissolution kinetics of starch in DMSO. Carbohydrate Research 2007, 342, 2604 [4] S Schmitz, AC Dona, P Castignolles, RG Gilbert, M Gaborieau, Assessment of the Extent of Starch Dissolution in Dimethyl Sulfoxide by 1H NMR Spectroscopy. Macromolecular Bioscience 2009, 9, 506. 104 Field of Research: Title of Project: 0204 0299 0306 Advanced Water Signal Suppression in in vivo NMR Spectroscopy Supervisor: Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Co-supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Campus project is offered and conducted: Campbelltown Background (max 500 words) In mammalian tissue, the common metabolites (e.g., tCr and NAA) used in NMR based disease diagnosis are present in concentrations several orders of magnitude smaller than water. Consequently, in vivo proton NMR spectra are overwhelmed by the extremely strong water signal, thereby preventing accurate detection of metabolites and thus the diagnostic value is unreliable. In this study, advanced water signal suppression techniques will be developed for better detection of metabolites and thus more accurate NMR based disease diagnoses. (Would suit students interested in Biology/Chemistry/Medical Physics/MRI/NMR) Aim of Study: To build advanced water signal suppression techniques for in vivo NMR spectroscopy Methods: Nuclear Magnetic Resonance Spectroscopy Ethics Application Requirements: Not Applicable Key References: 5. S.W. Provencher, Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnetic Resonance in Medicine, 1993. 30(6): p. 672-679. 6. G. Zheng and W. S. Price. Solvent Signal Suppression in NMR. Prog.NMR Spectrosc. 56 (3): 267-288, 2010. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 105 Field of Research: Title of Project: 0204 0303 0306 Supervisor: Decode Nature’s Way of Detoxification – NMR Studies on Dissolved Organic Matter in Australian Aquatic Systems Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Co-supervisor: Prof William S Price Campus project is offered and conducted: Email: [email protected] Telephone: 4620 3336 Campbelltown Background (max 500 words) Like ourselves, mother nature has many methods for detoxification. Dissolved organic matter (DOM) plays a major role in natural detoxification in aquatic systems. In fresh water, many harmful versions of heavy metals (e.g., methylmercury) latch onto DOM then are more likely broken down into harmless compounds by sunlight. In sea water, however, these nasty metal complexes tend to latch onto salt (i.e., sodium chloride) instead of DOM and therefore are far more likely accumulated through the food chain, according to studies by a US researcher. In this study, the key chemical components of the various DOM in Australian aquatic systems will be identified, their roles in the natural detoxification will be revealed, and environmental factors (e.g., salt) affecting the detoxification process will be identified. (Would suit students interested in Biology/Chemistry/NMR/Physics) Aim of Study: To unveil the role of each key chemical component of DOM in natural aquatic detoxification. Methods: Nuclear Magnetic Resonance Spectroscopy, Fluorescence Spectroscopy, Size Exclusion Chromatography Ethics Application Requirements: Not Applicable Nuclear Magnetic Resonance Spectroscopy, Fluorescence Spectroscopy, Size Exclusion Chromatography Key References: 7. G. Zheng and W.S. Price, Direct hydrodynamic radius measurement on dissolved organic matter in natural waters using diffusion NMR. Environ. Sci. Tech., 2012. 46(3): p. 1675-1680. 8. G. Zheng, T. Stait-Gardner, P.G. Anil Kumar, A.M. Torres, and W.S. Price, PGSTE-WATERGATE: An STE-based PGSE NMR sequence with excellent solvent suppression. J. Magn. Reson., 2008. 191: 159-163. 9. G. Zheng and W.S. Price, Solvent signal suppression in NMR. Prog. Nucl. Magn. Reson. Spec., 2010. 56: 267-288. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 106 Field of Research: Title of Project: 0204 0303 0304 0306 Expanding the Boundaries and Applications of Diffusion NMR Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Allan Torres Email: [email protected] Telephone: 4620 3459 Campus project is offered and conducted: Campbelltown Background (max 500 words) Diffusion NMR is routinely used to study various molecular properties, and interactions occurring in solution. This technique is also valuable in MRI as it can be used to probe microscopic structures in biological tissues. Recently, longlived singlet spin states have been used in NMR diffusion and diffusion-diffraction studies. Unlike regular spin coherences, singlet spin states have significantly longer lifetimes on the order of tens of seconds to a minute making it feasible to study extremely slowly diffusing molecules. In diffusion-diffraction studies, long lived singlet states can potentially be useful for probing structures with larger characteristic distances. In this project, the restricted diffusion of test molecules in glass and flexible silica capillaries will be investigated by utilising singlet spin states and various NMR coherences. The feasibility of performing NMR diffusion experiments in a single capillary with internal diameter of 10-200 micrometers will also be studied. (Would suit students interested in NMR/Physical Chemistry/Physics) Aim of Study: To characterise NMR diffusion in capillaries using various spin coherences and singlet spin states. Methods: Nuclear Magnetic Resonance Spectroscopy Ethics Application Requirements: Not Applicable Key References: 13. M. Carravetta and M.H. Levitt, Long-lived nuclear spin states in high-field solution NMR. J. Am. Chem. Soc. 126 (2004) 6228-6229. 14. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 15. N.N. Yadav, A.M. Torres and W.S. Price, NMR q-space imaging of macroscopic pores using singlet spin states. J. Magn. Reson. 204 (2010) 346-348. 16. A.M. Torres, B. Ghadirian and W.S. Price, Diffusion-diffraction using singlet spin states and various NMR coherences in a J-coupled AX spin system. RSC Advances 8 (2012) 3352-3360. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 107 Field of Research: Title of Project: 0204 0299 0304 0306 Investigating Biostructures using NMR/MRI Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Tim-Stait-Gardner Email: [email protected] Telephone: 4620 3114 Campus project is offered and conducted: Campbelltown Background (max 500 words) Biological tissue is not just an amorphous arrangement of cells. Indeed most tissue has an underlying structure composed of microscopic components as in muscle fibres or, as has more recently been realised, fibre tracts in brain tissue. Although the tracts might ultimately be macroscopic, they are composed of microscopic components. Such structures are not only involved in normal biological function, but also in diseased states, such as multiple sclerosis, epilepsy, and Alzheimer’s disease. Traditional techniques used to visualise such structures are not only limited in their application, but often these methods are invasive and tedious. In this project new NMR/MRI diffusion methods will be used to characterise tissue microstructure on a microscopic scale well below the resolution that is achievable using standard MRI sequences. In addition, the student would participate in the development of new NMR/MRI methods aimed at elucidating sample microstructure. (Would suit students interested in Biology/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To characterise a variety of tissue microstructures (mainly brain and muscle) and to participate in the development of new NMR techniques with this purpose. Methods: Nuclear Magnetic Resonance Spectroscopy and Imaging Ethics Application Requirements: May be necessary for some tissue samples. Key References: 10. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 11. S. Mori, J. Zhang, Principles of diffusion tensor imaging and its applications to basic neuroscience research, Neuron 51 (2006) 527-539. 12. P. Callaghan, Principles of Nuclear Magnetic Resonance Microscopy, Oxford University Press 1994. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 108 Field of Research: Title of Project: 0204 0299 0303 0306 Investigating Phantoms and Biostructures using NMR/MRI Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Tim-Stait-Gardner Email: [email protected] Telephone: 4620 3216 Dr Scott A Willis Campus project is offered and conducted: [email protected] 4620 3114 Campbelltown Background (max 500 words) Biological tissue is not just an amorphous arrangement of cells. Indeed most tissue has an underlying structure composed of microscopic components as in muscle fibres or, as has more recently been realised, fibre tracts in brain tissue. Although the tracts might ultimately be macroscopic, they are composed of microscopic components. Such structures are not only involved in normal biological function, but also in diseased states, such as multiple sclerosis, epilepsy, and Alzheimer’s disease. Traditional techniques used to visualise such structures are not only limited in their application, but often these methods are invasive and tedious. In this project new NMR/MRI diffusion methods will be used to characterise microstructure of suitable phantom (e.g., gels, capillaries) and tissue samples on a microscopic scale well below the resolution that is achievable using standard MRI sequences. In addition, the student would participate in the development of new NMR/MRI methods aimed at elucidating sample microstructure. (Would suit students interested in Biology/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To characterise a variety of microstructures in phantom samples (e.g., gels, capillaries) as well as tissues (e.g., brain, muscle) and to participate in the development of new NMR techniques with this purpose. Methods: Nuclear Magnetic Resonance Spectroscopy and Imaging Ethics Application Requirements: Not Applicable Key References: 10. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 11. S. Mori, J. Zhang, Principles of diffusion tensor imaging and its applications to basic neuroscience research, Neuron 51 (2006) 527-539. 12. P. Callaghan, Principles of Nuclear Magnetic Resonance Microscopy, Oxford University Press 1994. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 109 Field of Research: Title of Project: 0204 0299 0303 0306 Investigating Restricted Diffusion using NMR Techniques Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Bahman Ghadirian Email: [email protected] Telephone: 4620 3216 Campus project is offered and conducted: Campbelltown Background (max 500 words) Modelling self-diffusion in complicated geometries is of fundamental importance in many areas of science including medicine. Modelling diffusion-controlled reactions - which occur widely in chemical, and biochemical systems, and nuclear magnetic resonance diffusion experiments in bounded systems, provide many prominent examples of where such modelling is required. Using a simple cellular system as an example, a reacting species diffuses to the enzymatic membrane and then reacts in some way, being either transformed into a product, becoming bound to the surface or transported through the surface. The nature of the interaction at the surface determines the boundary conditions in the modelling. Presently only solutions for some simple geometries are available. This is a serious impediment as most real-world structures that chemical reactions occur in have complicated geometries. Thus, there is a need to develop techniques for modelling diffusive processes near surfaces which are applicable to different geometries and arbitrary boundary conditions. (Would suit students interested in Biology/Chemistry/Mathematics/Medical Physics/MRI/NMR) Aim of Study: To develop theoretical and experimental method for investigating diffusion in restricted systems and studying their application. Methods: Analytical modelling and numerical computer programming in Mathcad or Matlab, and testing the models using NMR experiments. Ethics Application Requirements: Not Applicable Key References: 19. C. H. Neuman, J. Chem. Phys. 60, 4508 (1974). 20. S. D. Traytak and W. S. Price, J. Chem. Phys. 127, 184508 (2007). 21. G. A. Truskey, F. Yuan, and D. F. Katz, Transport Phenomena in Biological Systems. (Pearson, London, 2004). 22. W. S. Price, NMR Studies of Translational Motion. (Cambridge University Press, Cambridge, 2009). 23. D. G. Duffy, Mixed Boundary Value Problems. (Chapman & Hall / CRC, New York, 2008). 24. B. Ghadirian, A. M. Torres, N. N. Yadav, and W. S. Price. J. Chem. Phys. 138:094202-1-094202-11 (2013). This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 110 Field of Research: Title of Project: 0204 0301 0303 0306 Investigation of diffusive averaging and viscosity effects in bimodal polymer solutions Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Assoc. Prof. Gary Dennis [email protected] 9685 9939 Dr Scott A Willis [email protected] 4620 3114 Campus project is offered and conducted: Campbelltown Background (max 500 words) The most fundamental form of molecular transport is self-diffusion – the random motion of molecules – and measurements of which provide information on the size of the molecule as well as any influences from restrictions/obstructions (e.g., diffusion in a cell or porous rock) or aggregation processes (e.g., drug-binding). A powerful, versatile and non-invasive method for measuring self-diffusion is pulse gradient spin-echo (PGSE) nuclear magnetic resonance (NMR). However, measurements of self-diffusion in polydisperse systems (e.g., polymer solutions with different molecular weight polymers present or aggregating proteins) is complicated by diffusive averaging effects since the NMR signals are the same or overlapped. Studying diffusive averaging in bimodal polymer solutions is of great significance as synthetic (e.g., polystyrene) and natural (e.g., proteins) polymers are inherently polydisperse. In this project, diffusive averaging will be studied for different bimodal polymer solutions (i.e., two molecular weights or two types of polymers present) of either chemically identical polymers of different molecular weights or mixtures of chemically different polymers of different or similar molecular weights. Several types of polymers could be considered for this study. Measurements of the viscosity of bimodal and monomodal polymer solutions will help to elucidate the diffusive averaging processes. (Would suit students interested in Physical chemistry/Mathematics/NMR) Aim of Study: To use NMR diffusion measurements and viscosity measurements to develop better models for diffusive averaging phenomena. Methods: Viscometry and NMR diffusometry. Ethics Application Requirements: Not Applicable Key References: 9. Price, W. S., NMR Studies of Translational Motion. Cambridge University Press: New York, 2009. 10. Willis, S. A.; Dennis, G. R.; Zheng, G.; Price, W. S. Macromolecules 2010, 43, 7351-7356. 11. Willis, S. A.; Price, W. S.; Eriksson-Scott, I. K.; Zheng, G.; Dennis, G. R. J. Mol. Liq. 2012, 167, 110-114. 12. Callaghan, P. T.; Pinder, D. N. Macromolecules 1985, 18, 373-379. 111 Field of Research: Title of Project: 0204 1103 1112 0306 MRI-based Electron Density Mapping for Radiotherapy Treatment Planning Supervisor: Prof William S Price Email: Co-supervisor: Dr Stephen Bosi (UNE) Email: [email protected] Telephone: 4620 3336 Telephone: Other members of the Nanoscale Research Group Campus project is offered and conducted: Campbelltown Background (max 500 words) Radiation therapy is a recommended treatment for approximately half of cancer cases [Delaney et al 2005]. Accurate planning of radiation dose requires both a picture of a patient's tissues and a map of the "electron density" of these tissues, currently obtained using CT (or "CAT") scans which use ionising radiation. At present an electron density (ED) map derived from a CT of the patient is the minimum requirement for treatment planning (TP) for external beam radiotherapy. Magnetic resonance imaging (MRI) scans actually provide a clearer tissue image than CT scans (and without using ionising radiation), but traditional medical MRI methods cannot provide a density map – at least not at the present time. Development of a new method which allows MRI to be used to measure tissue composition AND density would eliminate the extra radiation dose of a CT scan and streamline treatment planning. (Would suit students interested in Biology/Chemistry/Medical Physics/NMR) Aim of Study: The aim is to develop a method allowing MRI scanners to provide a tissue density map which is required for accurate radiation dose planning for radiation therapy. Methods: MRI Experiments + Analysis Ethics Application Requirements: Not Applicable Key References: 12. Delaney G., Jacob S., Featherstone C. et al. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer 104 1129-1137 (2005). 13. Khan F.M. "The Physics of Radiation Therapy" - 3rd ed., Lippincott & Wilkins. Philadelphia USA, 2003. 14. Wu Y., Reese T.G., Cao H., et al. Bone Mineral Imaged In Vivo by 31P Solid State MRI of Human Wrists J. Magn. Reson. Imaging. 34, 623–633 (2011). This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 112 Field of Research: Title of Project: 0204 0299 0303 0306 NMR Simulation using Symbolic Algebra Supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Co-supervisor: Dr Tim-Stait-Gardner Email: [email protected] Telephone: 4620 3216 Campus project is offered and conducted: Campbelltown Background (max 500 words) Understanding spin-dynamics is of fundamental importance for NMR students. However, in many instances to understand such complicated theory we must resort to computer simulation, which turns boring memorization into exciting practice. Numerical and symbolic algebra simulation programs can be used for the development of new NMR pulse sequences. In this project students will perform NMR simulations based on a full understanding of spindynamics to enhance the development of new NMR methods (e.g. water suppression and diffusion measurements). Exact numerical simulations of NMR experiments are often required for the development of new techniques and for the extraction of structural and dynamic information from the spectra. (Would suit students interested in Mathematics/MRI/NMR/Physics) Aim of Study: In this project, user friendly liquid state NMR simulation software will be developed based on density matrix, product operator and quaternion theories by the use of symbolic algebra software (e.g. Mathematica, Maple). The newly developed software will be distributed around UWS to assist NMR teaching and scientific research. Methods: Nuclear Magnetic Resonance Spectroscopy and computer simulation. Ethics Application Requirements: Not Applicable Key References: 5. W.S. Price, NMR Studies of Translational Motion, Cambridge University Press, Cambridge, 2009. 6. R.P.F. Kanters et al., A Computer-Algebra Application for the Description of NMR Experiments Using the ProductOperator Formalism, J. Magn. Reson. 101, 23-29, 1993. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 113 Field of Research: Title of Project: 0204 0303 0304 0306 Quantitative Composition-Flavour Relationships Supervisor: Dr Gang Zheng Email: [email protected] Telephone: 4620 3729 Co-supervisor: Prof William S Price Email: [email protected] Telephone: 4620 3336 Campus project is offered and conducted: Campbelltown Background (max 500 words) Have you ever thought about why different wines have different tastes? What is controlling the flavour? What chemicals contribute to the flavour generation process? Are these chemicals staying as monomers or forming assemblies in the wine? The results of this study will answer all these tricky questions. (Would suit students interested in Biology/Chemistry/NMR/Physics/Statistics/Wine tasting) Aim of Study: To build an NMR-based wine tasting machine Methods: Nuclear Magnetic Resonance Spectroscopy Pattern Recognition Ethics Application Requirements: Not Applicable Key References: 5. Hu, N., D. Wu, K. Cross, S. Burikov, T. Dolenko, S. Patsaeva, and D.W. Schaefer, Structurability: A collective measure of the structural differences in vodkas. Journal of Agricultural and Food Chemistry, 2010. 58(12): p. 73947401. 6. Polášková, P., J. Herszage, and S.E. Ebeler, Wine flavor: Chemistry in a glass. Chemical Society Reviews, 2008. 37(11): p. 2478-2489. This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 114 Environmenal Sciences Including: Environmental Science and Management 115 Environmental Science and Management 116 Title of Project: Turtle Conservation Team: Optimising Management to Address Turtle Declines (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Turtles are evolutionary survivors. Their hard protective shell and longevity has allowed them to survive 220 million years of natural selective pressures. But the combination of rapid, human-induced, changes (invasive species, harvesting and river regulation) has led to nearly half of all turtle fauna either endangered or extinct in the wild and without strategic intervention, much of the turtle lineage will be extinct by the end of the 21st century. Besides their conservation value as an iconic native vertebrate, the rapid decline of freshwater turtles may have far greater implications for the entire ecosystem, because their biomass is a similar magnitude to fis, and their role in the food chain is likely to be complex and diverse, yet completely unknown. Given their longevity, however, anthropogenic changes to the River ecosystem through the introduction of invasive species and changes in water management may only now be manifesting into population declines and local extinctions. This project will team with management agencies throughout the Murray River to identify and address threats to freshwater turtles, which are endangered in many states of Australia. The project will determine predation rates on turtle nests and nesting females, trial new fox management options, and assess turtle nesting preferences. TurtleSAT (TurtleSAT.org.au) will be used in this project, which will allow GIS spatial analysis to develop broad-scale predictive maps of turtle and fox ‘hotspots’ throughout the Murray River. You will be part of a large team of researchers, including post-docs and PhD students. You will have the opportunity to work closely with researchers from the University of Sydney, University of NSW and University of Canberra, as well as management agencies from three states. Animal Ethics approval is required. 117 Title of Project: Turtle Conservation Team: Impact of Dams on Turtle Movement and Recruitment (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Turtles are evolutionary survivors. Their hard protective shell and longevity has allowed them to survive 220 million years of natural selective pressures. But the combination of rapid, human-induced, changes (invasive species, harvesting and river regulation) has led to nearly half of all turtle fauna either endangered or extinct in the wild and without strategic intervention, much of the turtle lineage will be extinct by the end of the 21st century. Besides their conservation value as an iconic native vertebrate, the rapid decline of freshwater turtles may have far greater implications for the entire ecosystem, because their biomass is a similar magnitude to fis, and their role in the food chain is likely to be complex and diverse, yet completely unknown. Given their longevity, however, anthropogenic changes to the River ecosystem through the introduction of invasive species and changes in water management may only now be manifesting into population declines and local extinctions. Many river and wetland systems are fragmented by dams and altered ecologically through flow regulation, increasing the likelihood of population isolation for many aquatic species. Hence knowledge about the distribution and connectivity of species across important ecosystems, like the Murray-Darling Basin, both at the population and genetic levels, is essential if we are to manage them properly. Distinct metapopulations may exist between dams, as well as, in billabongs that are disconnected from the river except during major floods. If dispersal regularly occurs from certain key sites within these metapopulations, gene frequencies may be homogenised and local adaptation to fox predation may be reduced. Radiotracking (Telemetry) and molecular nuclear markers will be used to provide estimates of gene flow between populations to assess impact altering flow and connectivity. You will be part of a large team of researchers, including post-docs and PhD students. You will have the opportunity to work closely with researchers from the University of Sydney, University of NSW and University of Canberra, as well as management agencies from three states. Animal approval is required. 118 Title of Project: Power of Citizen Science: Using WomSAT to Manage Wombat Road Mortalities (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Australia Wide Project Background WomSAT is a new community mapping tool to that employs citizen science to determine the location of wombats throughout Australia. Many of these sightings are of road mortalities. This project will employ WomSAT and advanced GIS mapping techniques to determine hotspots of mortality. Important habitat data at these hotspots will be collected to determine if consistent patterns exist, which will allow harm mitigation strategies to be implemented. The project will also explore the social aspects of citizen science and promote WomSAT among management groups. Human Ethics approval may be required. 119 Title of Project: Impact of Domestic Cats on Native Wildlife in Urban Fringes (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Blue Mountains Project Background This project will evaluate the impact of cats on native wildlife in the Blue Mountains. The project will specifically target domestic cats and their owners to determine perception versus reality of domestic cat impacts. We will employ new control devices that spray liquids on cats as they investigate lures. The liquid can deliver a toxin, but in this project will spray domestic cats with coloured dyes- the colour will depend how far into the bush the cat has wandered. Owners will be encouraged to report the colour on the cat and their location through a website/app. The project will work very closely with environmental officers from Blue Mountains City Council. Animal and Human Ethics approval is required. 120 Title of Project: Turtle Conservation Team: Ecological Function of Turtles (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Turtles are evolutionary survivors. Their hard protective shell and longevity has allowed them to survive 220 million years of natural selective pressures. But the combination of rapid, human-induced, changes (invasive species, harvesting and river regulation) has led to nearly half of all turtle fauna either endangered or extinct in the wild and without strategic intervention, much of the turtle lineage will be extinct by the end of the 21st century. Besides their conservation value as an iconic native vertebrate, the rapid decline of freshwater turtles may have far greater implications for the entire ecosystem, because their biomass is a similar magnitude to fis, and their role in the food chain is likely to be complex and diverse, yet completely unknown. Given their longevity, however, anthropogenic changes to the River ecosystem through the introduction of invasive species and changes in water management may only now be manifesting into population declines and local extinctions. The project will develop complex food webs in a range of habitats throughout eastern Australia. We will also manipulate turtle composition and abundance in experimental wetlands on the Hawkesbury campus and evaluate changes in food web dynamics and the relative importance of turtles on ecosystem function. The project will implement a large-scale experimental flood into Hawkesbury wetlands to evaluate the importance of regular inundations for food web dynamics and particular species of turtle. You will be part of a large team of researchers, including post-docs and PhD students. You will have the opportunity to work closely with researchers from the University of Sydney, University of NSW and University of Canberra, as well as management agencies from three states. Animal Ethics approval is required. 121 Biological Sciences Including: Biochemistry & Cell Biology Ecology Evolutionary Biology Genetics Microbiology Physiology Plant Biology Zoology 122 Biochemistry & Cell Biology 123 Title of Project: Role of tachykinin neuropeptides in the regulation of synaptic copper homeostasis. (FOR Code/s): 030201 (50%), 060105 (35%), 060112 (15%) Supervisor: Dr Christopher Jones Contact: [email protected], ph: 9685 9908 Co-supervisor: Dr Mark Jones Contact: [email protected] Location of Project: Parramatta Project Background Tachykinin neuropeptides are involved in diverse biological functions, including regulating neuroprotective and neuroinflammatory pathways in the brain. In a neuroprotective capacity, these peptides have been shown to protect against neurotoxic processes in Alzheimer’s disease, yet it is not clear how they achieve this. One feature of Alzheimer’s disease is the disruption of normal copper homeostasis in the brain. Normally, neurons can release the metal into the synapse where it is thought to modulate the activity of proteins, such as receptors, that function within the synapse. There is now evidence that some tachykinin neuropeptides are able to bind copper, and recent work from our laboratory has shown that one member, neurokinin B, can inhibit the uncontrolled cellular uptake of the metal into brain cells called astrocytes. Uncontrolled cellular copper uptake results in disruption to intracellular calcium levels, and also promotes formation of dangerous reactive oxygen species, and both processes contribute to cell death. We hypothesis that neurokinin B is a key member of synaptic copper homeostasis, which helps protect brain cells against copper-induced toxicity, and that loss of this activity contributes to cell death observed in Alzheimer’s disease. This project would suit someone with an interest in cell biology and biochemistry. Aim of Study: influence and control copper uptake into both neurons and astrocytes. Key questions to answer are: 9. Do the tachkinins completely inhibit copper uptake, or do they just ensure metal uptake occurs only via correct pathways? 10. Is the effect on astrocytes the same as neurons, or is the ability to control copper uptake cell specific? 11. Does copper remain bound to the tachykinins even in the presence of specific tachykinin receptors? 12. Does copper-bound NKB influence trafficking of the NKB-receptor to the nucleus? Methods: Cell culture of neurons and astrocytes, fluorescence spectroscopy, confocal microscopy, western blotting. Ethics Application Requirements: None required. Key References: Russino DR, McDonald E, Hejazi L, Hanson GR, Jones CE. The tachykinin neuropeptide Neurokinin B binds copper forming an unusual [Cu(II)(NKB)2] complex, and inhibits copper uptake into 1321N1 astrocytes. ACS Chem. Neurosci. 4(10), 1371-81, 2013. Grosas AB, Kalimuthu P, Smith AC, Williams PA, Millar TJ, Bernhardt PV and Jones CE. The tachykinin peptide neurokinin B binds Cu(I) and Ag(I) and undergoes quasi-reversible electrochemistry. Towards a new role for the peptide in the brain. Neurochem. Int. 70, 1-9, 2014 124 Title of Project: Elucidating the structure and metal-binding properties of peptides that regulate feeding in starfish. (FOR Code/s): 030201 (30%), 060105 (35%), 060112 (35%) Supervisor: Dr Christopher Jones Contact: [email protected], ph: 9685 9908 Co-supervisor: Dr Feng Li Contact: [email protected], ph 9685 9987 Location of Project: Parramatta Project Background The SALMFamides are a family of neuropeptides found in species of the phylum Echinodermata (e.g. starfish) where they appear to function as muscle relaxants. Starfish feed by everting their stomach over their prey and, as muscle relaxants, the SALMFamides help trigger stomach eversion. We have characterised two neuropeptides, called S1 and S2 where S1 is an octapeptide (GFNSALMF-NH2) and S2 is a dodecapeptide (SGPYSFNSGLTF-NH2). S2 is 10 times more potent than S1, and potency is a combination of both primary sequence and the structure adopted by the neuropeptide. Intriguingly, S2 is able to self-associate and is so far unique in this ability within the SALMFamide family. However, these peptides are cleaved from precursor proteins that contain at least seven other SALMFamides, and all are presumably functionally present at the same time. We don’t know if these other peptides can either self-associate or interact with each other to form dimers or larger structures. Based on sequence analysis of some SALMFamides, we predict that metals may help regulate association by acting as a link between different peptides. Understanding the mechanisms underlying starfish feeding may open new avenues for controlling crown-of-thorn feeding on corals of the Great Barrier Reef. This project would suit someone with an interest in protein structure and coordination chemistry. Aim of Study: This study will investigate the structure and metal-binding behaviour of six SALMFamide neuropeptides from Asterias rubens. Key aims to answer are: 13. Do any peptides undergo self-assocation to form dimers or higher order structures? 14. What conditions promote self-association? 15. Do any of the peptides bind metals – specifically copper, zinc or nickel, and what is the affinity for the different metal ions? 16. How do metal ions influence peptide structure – e.g. can metal-linked dimers or oligomers of different peptides be formed? Methods: Electronic spectroscopy, Nuclear magnetic resonance, Circular dichroism. Ethics Application Requirements: N/A. Key References: Otara C, Jones CE, Younan ND, Viles JH and Elphick MR. Structural analysis of the starfish SALMFamide neuropeptides S1 and S2: The N-terminal region of S2 facilitates self-association. BBA-Proteins and Proteomics. 1844, 358-265, 2014. Jones CE, Otara C, Younan ND, Viles JH and Elphick MR. Bioactivity and structural properties of chimeric analogs of the starfish SALMF-amide neuropeptides S1 and S2. BBA-Proteins and Proteomics, 1844, 1842-1850, 2014. 125 Title of Project: Investigation into the role of protein kinase CK2 in metal ion uptake by fluorescent imaging (FOR Code/s): 0601 Biochemistry and Cell Biology; 0605 Microbiology Supervisor: Dr Ming J Wu Contact: [email protected] Co-supervisor: Dr Yossi Buskila Contact: [email protected] Location of Project: UWS, Campbelltown Project Background Protein kinase CK2 is the first kinase discovered and many questions still remains open. It is certain, based on the accumulated findings of the past decades, that the kinase plays multiple roles in regulating cellular functions, including cell proliferation, cell cycle, and apoptosis. The fact that it is constitutively active demonstrates its prominence and necessity to the cell’s survival. Despite the intensive research activities on CK2, there is a clear deficiency of data addressing its potential role in metal ion homeostasis. In this project, by the means of metal-specific fluorescent imaging, the role of CK2 in metal ion uptake will be investigated using Saccharomyces cerevisiae and mammalian cell lines. The key advantage of S. cerevisiae is the availability of CK2 subunit knockout mutants (cka1∆, cka2∆, ckb1∆ and ckb2∆). The conservation of genes and biological processes between the yeast and mammalian cell makes the findings relatable from one to another. Fluorescent imaging is to be carried out for quantification of metal ion uptake by using specific fluorophores for aluminium (Al3+), calcium (Ca2+), zinc (Zn2+) and chromium (Cr6+). Aim of Study: To uncover the role of CK2 in metal ion uptake Methods: The experimental approaches include: (1) preparation of the yeast (wild type and mutants) and mammalian cells; (2) quantification of metal ions influx by fluorescent imaging. Ethics Application Requirements: Not applicable Key References: To be provided on request 126 Title of Project: Investigating the association between altered cholesterol and fat metabolism, and redox (antioxidant) balance and free radical accumulation/damage in cells. (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact:[email protected] Co-supervisor: Contact: Location of Project:Campbelltown campus Project Background Maintenance of an optimal redox environment in cells (i.e. reducing/oxidising) is critical for functioning of many cellular processes and for protecting cells against the damaging effects of reactive oxygen species (ROS). Cells are continually exposed to reactive oxygen species (ROS or free radicals) as part of normal metabolism. These ROS are toxic, affect redox balance, and have been implicated in many diseases including cancer, cardiovascular disease and arthritis. Key cellular systems (e.g. glutathione) maintain redox balance. Lipid metabolism and maintenance of an optimal redox environment are intimately linked through their requirement for NADPH as a cofactor. Substantial NADPH supplies are consumed in maintaining redox (antioxidant) systems as well as in the synthesis of lipids e.g. sterols (ergosterol/cholesterol) and fatty acids. Equally synthesis of sterols consumes appreciable levels of oxygen, and membrane sterol composition modulates oxygen diffusion. Sterols therefore may function in protecting of cells against oxygen or more specifically ROS (i.e. free radicals). Altered lipid metabolism, redox balance and/or ROS accumulation are associated with many diseases including, diabetes and neurodegenerative diseases including Alzheimer’s and Parkinson’s. Surprisingly an in depth understanding of how abnormal lipid metabolism affects redox/antioxidant defences, and detoxification of ROS has not been thoroughly investigated. Conversely how changes in redox/ROS affect lipid metabolism has not been studied in detail. Aim of Study: This project will study how the DNA synthesis and repair mechanisms of cells is impacted by changes in redox balance. The project also aims to study the converse, that is how changes in DNA homeostasis affect a cells ability to maintain redox balance and detoxification of reactive oxygen species. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) to study the extent to which lipid metabolic pathways, redox homeostasis and ROS production are inter-connected. These resources include novel redox sensing probes based on green fluorescent protein (roGFP) that can selectively measure dynamic changes in redox balance in real-time in live cells. Production of free radical species will also be measured. This project will use a range of instrumentation and techniques including flow cytometry, fluorescence microscopy and assays detecting DNA damage. The project will also exploit the vast resources of genome-wide deletion/overexpression strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, as well as gene libraries that allow researchers to selectively overexpress most genes in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to test almost any hypotheses. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 127 Title of Project: Investigating the link between DNA synthesis/repair, redox balance and production of free radicals (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact:[email protected] Co-supervisor: Contact: Location of Project:Campbelltown campus Project Background Maintenance of an optimal redox environment in cells (i.e. reducing/oxidising) is critical for functioning of many cellular processes and for protecting cells against the damaging effects of certain free radical species. Cells are equipped with key systems (e.g. glutathione) that maintain redox balance. Altered redox balance is associated with many diseases including, cancer, diabetes, neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases, and has been implicated as an important factor regulating cell growth and ageing. Cells of are continually exposed to reactive oxygen species (ROS or free radicals) as part of normal metabolism. These ROS are toxic, affect redox balance, and have been implicated in many diseases including cancer, cardiovascular disease, arthritis and those listed above. Altered lipid metabolism has also been associated with many of the above diseases. Maintenance and repair of DNA and maintenance of an optimal redox environment are closely linked through their requirement for NADPH as a cofactor. NADPH is used in the synthesis of DNA but is also used to keep redox/protective systems in balance. Combined treatments of cells with agents that affect redox systems in conjunction with DNA damaging agents has shown strong efficacy in treatment of some cancers. Surprisingly there an in depth understanding of how changes in DNA metabolism affect the ability of cells to maintain their redox environment and vice-versa is lacking. Aims: This project will study how the DNA synthesis and repair mechanisms of cells is impacted by changes in redox balance. The project also aims to study the converse, that is how changes in DNA homeostasis affect a cells ability to maintain redox balance and detoxification of reactive oxygen species. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) to study the extent to which lipid metabolic pathways, redox homeostasis and ROS production are inter-connected. These resources include novel redox sensing probes based on green fluorescent protein (roGFP) that can selectively measure dynamic changes in redox balance in real-time in live cells. Production of free radical species will also be measured. This project will use a range of instrumentation and techniques including flow cytometry, fluorescence microscopy and assays detecting DNA damage. The project will also exploit the vast resources of genome-wide deletion/overexpression strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, as well as gene libraries that allow researchers to selectively overexpress most genes in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to test almost any hypotheses. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 128 Title of Project: The interaction between mitochondrial function and sphingolipid metabolism. Implications for programmed cell death and human diseases. (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact:[email protected] Co-supervisor: Contact: Location of Project:Campbelltown campus Project Background Sphingolipids play key roles in a broad range of cellular processes including: the formation of lipid micro domains “rafts” in membrane bilayers, that influence protein sorting and signal transduction; signaling molecules in cell differentiation, growth and cell cycle progress/arrest, cholesterol metabolism and stress signaling; and immune function, endocytosis and programmed cell death. Due to the role of sphingolipids in important cellular processes the impact of altered sphingolipid metabolism can have very serious consequences for cells. Altered sphingolipid metabolism has also been shown to play an important role in the pathobiology of diseases including: cancer, diabetes and metabolic syndrome; heart disease; Alzheimer’s disease; Niemann-Pick; and immune dysfunction. In some cancers altered sphingolipid homestasis appears to play a key role in disease progression. Crucially, despite the role of sphingolipids in a diverse range of serious human diseases, on a global or a “systems-wide” level very little is known of how the broad array of cellular functions influence sphingolipid homeostasis and/or vice-versa. Recently we have identified novel links between mitochondrial function and sphingolipid metabolism. This is a two bidirectional effect whereby altered mitochondrial function impacts on sphingolipid metabolism, and conversely, we have identified cases were altered sphingolipid metabolism disrupts mitochondrial respiration. Aims: To investigate how mitochondrial dysfunction (e.g. respiratory ) leads to abnormal sphingolipid homeostasis, and, vice-versa how defects in sphingolipid metabolism impact mitochondrial function, including respiratory capacity. This study also aims to identify on a genome-wide level how the various process conducted in cells affects sphingolipid metabolism. The findings will help us to better understand the factors that contribute to abnormal sphingolipid metabolism and inform our understanding of diseases (e.g. metabolic syndrome, cancer, neurodegenerative diseases) where altered sphingolipid metabolism has been implicated. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) as well as leading edge techniques and resources. The project will exploit the genome-wide deletion strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, lipid analyses, as well as suite of powerful yeast strain libraries that allow us to selectively manipulate almost all genes (deletion or overexpression) in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to readily test most hypotheses. This project will utilise sophisticated analytical methodology including flow cytometry, mass spectrometry and fluorescent microscopy If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 129 Title of Project: Understanding why depleting the key antioxidant, glutathione, leads to catastrophic loss of mitochondrial DNA in cells. (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact: [email protected] Co-supervisor: Contact: Location of Project: Campbelltown campus Project Background Glutathione is an essential molecule that acts as a key redox buffer, antioxidant and protectant against toxins such as heavy metals and drugs. Decreased cellular levels of GSH in cells leads to a range of detrimental effects including increased accumulation of free radicals and cellular damage, defects in protein folding and severe disturbance of iron metabolism. Glutathione is non to decrease during the ageing process and GSH depletion has been linked with numerous disease process including Alzheimer’s disease, Parkinson’s disease, diabetes, and alcoholic liver disease. In the latter case depletion of mitochondrial glutathione has been implicated in the disease process. Glutathione depletion is also known to occur as part of the natural ageing process by also can be caused acutely through exposure to many toxins including heavy metals, poisons and medications (e.g. paracetamol). We have recently demonstrated that GSH depletion in yeast leads to a catastrophic and complete loss of the mitochondrial DNA from cells (mtDNA). Loss of mDNA was found to correlate with iron overload in mitochondria, a burst of reactive oxygen species (ROS) production. While we have some key pieces of the puzzle, it is still unclear what the precise mechanisms underlying mtDNA loss are. Since damage or loss of mtDNA poses serious implications for human health and disease the significance of understanding the mechanism(s) involved are anticipated to be far reaching. Aims: This project will aim to elucidate how the mechanisms through which glutathione depletion affects mtDNA integrity. The project will also aim to study mitochondrial glutathione homeostasis using high through put flow cytometry and novel in vivo redox probes based on roGFP (redox GFP). Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast), including genome-wide collections of strains that either have a gene deleted or conversely overexpressed. The project will involve the use of highly sophisticated flow cytometry methods to analyse mtDNA loss, mitochondrial energization, mitochondrial redox and ROS production. These resources used will include novel redox sensing probes based on green fluorescent protein (roGFP) that can selectively measure dynamic changes in redox balance in mitochondria in real-time. Production of free radical species will also be measured using fluorescent dyes. This project will use a range of instrumentation and techniques including flow cytometry, fluorescence microscopy and assays detecting mitochondrial DNA damage. The project will also exploit the vast resources of genome-wide deletion/overexpression strain collections, drug treatments, a range of recombinant DNA biochemical assays, as well as gene libraries that allow researchers to selectively overexpress most genes in the yeast genome. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 130 Title of Project: Molecular investigation into the effect of manganese and hydrogen peroxide on the phenotype of yeast hom6Δ mutant (FOR Code/s): 0601 Biochemistry and Cell Biology; 0605 Microbiology Supervisor: Dr Ming J Wu Contact: [email protected] Co-supervisor: Dr Cindy Kersaitis Contact: [email protected] Location of Project: UWS, Campbelltown Project Background HOM6 encoding homoserine dehydrogenase is a major gene in the aspartate pathway which leads to biosynthesis of threonine, methionine and cysteine. The phenotypes of the gene deletion mutant (hom6∆) in a variety of cultural conditions have previously provided meaningful insights into the biological roles of HOM6 and its upstream intermediate metabolites such as aspartate β-semialdehyde. This metabolic pathway is heavily targeted by the recent research for antifungal drug development because of its uniqueness for fungi and its absence in mammalian hosts. We have demonstrated previously that both manganese (Mn2+) and hydrogen peroxide (H2O2) can promote the growth of hom6Δ, with the latter exerting such effect only under anaerobic condition. This Honours project intends to delineate the underlying molecular mechanism for the effect of these two agents on hom6Δ mutant. Aim of Study: To delineate the underlying molecular mechanism for the positive effect of Mn2+ and H2O2 on the growth of hom6Δ mutant Methods: Three experimental approaches will be carried out in this project, namely, (1) manipulation of aspartic acid pathway by supplementation of specific metabolites; (2) manipulation of aspartic acid pathway by enzyme inhibitors; (2) molecular analysis of gene expression by quantitative polymerase chain reaction (qPCR). It is anticipated that the outcomes should provide a basis for the underlying molecular mechanism of the findings with Mn2+ and H2O2 on the growth of hom6Δ mutant Ethics Application Requirements: Not applicable Key References: To be provided on request 131 Title of Project: Efficacy and Mechanism of Chinese herbal medicine in treatment of colorectal cancer (FOR Code/s): Biochemistry and Cell Biology (0601) Supervisor: Qihan Dong Contact: Email: [email protected] Co-supervisor: Contact: Location of Project: Campbelltown Project Background Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females worldwide with over 1.2 million new cases and ~600,000 deaths annually [1]. Although early diagnosis has identified more patients with negative lymph nodes metastasis leading to a successful surgical removal of CRC, about 20% of these patients have recurrences and die of disease within 5 years (2). In patients with positive lymph nodes metastasis, the recurrence rate is as high as 40%, despite the chemotherapy following surgery (3). Hence, patients with CRC are increasingly exploring the use of phytomedicines in particular Chinese herbal medicine (CHM) for treatment and prevention of disease recurrence. Dr Zhong Li (Professor, Beijing University of TCM) has examined numerous recipes of CHM, and selected some to treat patients with CRC at his Beijing Clinic. Great successes have been reported and published in Chinese medical literature. However, how these CHM influence CRC cancer cell survival and growth is not clear. We established collaboration with Professor Li in 2013 to verify if and how these CHM affect CRC cells using an in vitro platform. The preliminary results have demonstrated that two recipes possess potent anti-proliferative effect against CRC cancer cells compared with other CHMs. Aim of Study: To determine mechanism whereby the two recipes of CHM exert the suppressive effect on CRC cell proliferation. Methods: Honours students will learn cell culture, CHM treatment, SYBR Green Analysis, immunoblot and flow cytometry. Ethics Application Requirements: No Key References: 1. Siegel, R., D. Naishadham, and A. Jemal, Cancer statistics, 2012. CA Cancer J Clin, 2012. 62(1): p. 10-29. 2. Chang, G.J., et al., Practical application of a calculator for conditional survival in colon cancer. J Clin Oncol, 2009. 27(35): p. 5938-43. 3. Marshall, J.L., et al., Adjuvant Therapy for Stage II and III Colon Cancer: Consensus Report of the International Society of Gastrointestinal Oncology. Gastrointest Cancer Res, 2007. 1(4): p. 146-54. 132 Title of Project: Mechanism of cell cycle re-entry by quiescent prostate cancer cells (FOR Code/s): Biochemistry and Cell Biology (0601) Supervisor: Qihan Dong Contact: Email: [email protected] Co-supervisor: Contact: Location of Project: Campbelltown Project Background Cancers are made up of both actively dividing and "resting" cancer cells. These resting or quiescent cancer cells are thought to be central to relapse, after actively dividing cancer cells are eliminated by chemo- or radio-therapy. One can envisage if cell cycle re-entry by these quiescent cancer cells is blocked, cancer recurrence can be prevented or delayed. However, the regulatory signals required for quiescent cancer cells to re-enter the cell cycle have not been determined. Identification of these signals will provide needed molecular targets for preventing cancer recurrence. We have found a list of genes that are over-expressed in advanced form of prostate cancer compared with either normal prostate or organ-confined prostate cancer. The role these gene products play in promoting cell cycle re-entry by quiescent prostate cancer cells is unclear. Aim of Study: To determine the effect of gene products that are over-expressed in advanced form of prostate cancer in cell cycle reentry by quiescent prostate cancer cells. Methods: Honours students will learn cell culture and immunoblot and use these techniques to determine the identified gene product (proteins) in cell cycle re-entry by quiescent cancer cells. Ethics Application Requirements: Not required as all are in vitro studies. Key References: Desoize B, Jardillier J. Multicellular resistance: a paradigm for clinical resistance? Crit Rev Oncol Hematol 2000;36:193207. 133 Field of Research: Molecular Physiology / Neuroscience (FOR Code/s): 1109, 0606, 1101, 0601 Title of Project: Defining Molecular Mechanisms Underlying Multiple Sclerosis Supervisor: Prof. Jens Coorssen Email: [email protected] Co-supervisor: Dr. Simon Myers Email: [email protected] Campus project is offered and conducted: Campbelltown Telephone: 46203802 Telephone: 46203383 Background (max 500 words) Multiple Sclerosis (MS) is a CNS disorder of as yet undefined aetiology. It has long been assumed to be an autoimmune disorder, and there is no doubt that such a component is an active part of the disease process and its progression. Nonetheless, it has also become apparent that this aspect alone does not necessarily explain the initiation/development of MS; a newer hypothesis holds that MS may first and foremost be a degenerative disorder, specifically an oligodendrocytosis. We are currently engaged in a research project to better distinguish between these aspects of MS using different mouse models as well as blood/white cell samples from human patients. The outcomes will be important in terms of enabling earlier and/or better identification of (i) MS patients; (ii) prognostic indicators; and (iii) new therapeutic targets. Aim of Study: Hypothesis – MS is fundamentally a degenerative disease. Aims - Use detailed proteomic or lipidomic analyses to better understand molecular changes occurring in mouse models of MS - Identify specific CNS changes; - Identify specific changes in white cells Specific details for an Honours project can be discussed and refined with a suitable candidate. Methods: We have well established protocols for tissue processing, protein and lipid extraction, and all aspects of (i) proteomic analyses using a refined, quantitative 2D gel approach; and (ii) lipidomic analyses using a refined, quantitative high performance thin layer chromatography approach. Ethics Application Requirements: Both human (hospital) and animal ethics approval are in place. 134 Field of Research: Molecular Physiology / Proteomics (FOR Code/s): 0601, 1101 Title of Project: Toward Single-Cell Proteomics Supervisor: Prof. Jens Coorssen Email: [email protected] Co-supervisor: Dr. Chandra Malladi Email: [email protected] Campus project is offered and conducted: Campbelltown Telephone: 46203802 Telephone: 46203813 Background We lack fundamental understanding of molecular mechanisms underlying most serious healthcare burdens, or why therapeutics often fail after initially proving effective. Identifying meaningful disease biomarkers and understanding molecular mechanisms demands far more rigorous analyses than provided by many research approaches popularised over the last decade. As proteins are the active players in all cellular functions, alterations in their structure, function, and/or abundance underlie disease states; they are thus the fundamental and rational targets of virtually all drugs. Large-scale, quantitative, and systematic analysis of all the proteins in a sample (i.e. top-down proteomics) offers the most direct path to understanding molecular mechanisms and thus identification of new therapeutic targets and biomarkers. However, a more recently recognised need is for single cell proteomics to understanding clinically critical cell heterogeneities, including those responsible for cancer metastasis. Aim of Study: Over the last several years we have developed a combined and highly refined protocol for sample handing, 2D gel electrophoresis, protein detection, and imaging that yields top-down proteomic analyses of the highest resolution and sensitivity [1-3]. We are now aiming to progressively drive these analyses to the single-cell level through a series of further refinements in combination with other ongoing analytical work in the group. Here we test the hypothesis that simply altering the physical parameters of the resolving gels will enable substantial decreases in the total amount of starting material required for an effective top-down proteomic analysis. Methods: Systematic testing and refinement of alterations in the size and composition of protein resolving gels; this will also likely include developing alternate handling and protein extraction methods more compatible with the analysis of single cells. Preliminary results have established this as a feasible approach. Ethics Application Requirements: not applicable Key References: 1. Wright, E.P., Partridge, M.A., Padula, M.P., Gauci, V.J., Malladi, C.S., and Coorssen, J.R. (2014) Top-down proteomics: Enhancing 2D gel-electrophoresis from tissue processing to high sensitivity protein detection. Proteomics 14, 872-889. 2. Gauci, V.J., Padula, M.P., and Coorssen, J.R. (2013) Coomassie blue staining for high sensitivity gel-based proteomics. Journal of Proteomics 90, 96-106. 3. Wright, E.P., Prasad, K.A.G., Padula, M.P., and Coorssen, J.R. (2014) Deep Imaging: How much of the Proteome does current top-Down technology already resolve? PLoS ONE 9(1): e86058. 135 Field of Research: Molecular Physiology / Proteomics (FOR Code/s): 0601, 1101 Title of Project: Improving Protein Identifications Using Mass Spectrometry Supervisor: Prof. Jens Coorssen Email: [email protected] Co-supervisor: Dr. Chandra Malladi Email: [email protected] Campus project is offered and conducted: Campbelltown Telephone: 46203802 Telephone: 46203813 Background We lack fundamental understanding of molecular mechanisms underlying most serious healthcare burdens, or why therapeutics often fail after initially proving effective. Identifying meaningful disease biomarkers and understanding molecular mechanisms demands far more rigorous analyses than provided by many research approaches popularised over the last decade. As proteins are the active players in all cellular functions, alterations in their structure, function, and/or abundance underlie disease states; they are thus the fundamental and rational targets of virtually all drugs. Large-scale, quantitative, and systematic analysis of all the proteins in a sample (i.e. top-down proteomics) offers the most direct path to understanding molecular mechanisms and thus identification of new therapeutic targets and biomarkers. Such gel-resolved proteins are excellent substrates for proteolytic digestion prior to LC/MS analysis of peptides to then identify (ID) proteins from a number of different databases; ID quality hinges on several criteria, including overall sequence coverage - this is often proportional to the amount of starting material. The issue is how to effectively handle lower abundance proteins that we now routinely detect using our refined proteome analyses. Aim of Study: We have developed a combined and highly refined protocol for sample handing, 2D gel electrophoresis, protein detection, and imaging that yields top-down proteomic analyses of the highest resolution and sensitivity [1-3]. Thus, we routinely detect low abundance proteins that require high quality IDs. What is needed is a systematic evaluation of in-gel protein spot density (i.e. amount of protein) vs. trypsin digestion conditions (i.e. concentration, time, & temperature) to ensure optimal peptide yields and thus high quality protein IDs. Here we test the hypothesis that optimising digestion parameters relative to spot density enables optimal & consistent protein IDs. Methods: Systematic testing and refinement of digestion conditions relative to protein spot density, followed by LC/MS analyses and database searching to ensure the best possible protein IDs. Preliminary results have established this as a feasible approach. Ethics Application Requirements: not applicable Key References: 1. Wright, E.P., Partridge, M.A., Padula, M.P., Gauci, V.J., Malladi, C.S., and Coorssen, J.R. (2014) Top-down proteomics: Enhancing 2D gel-electrophoresis from tissue processing to high sensitivity protein detection. Proteomics 14, 872-889. 2. Gauci, V.J., Padula, M.P., and Coorssen, J.R. (2013) Coomassie blue staining for high sensitivity gel-based proteomics. Journal of Proteomics 90, 96-106. 3. Wright, E.P., Prasad, K.A.G., Padula, M.P., and Coorssen, J.R. (2014) Deep Imaging: How much of the Proteome does current top-Down technology already resolve? PLoS ONE 9(1): e86058. 136 Field of Research: Molecular Physiology / Neuroscience (FOR Code/s): 1109, 0601, 0606 Title of Project: Examining Molecular Mechanisms Underlying Ca2+ Triggered Neurotransmitter Release Supervisor: Prof. Jens Coorssen Email: [email protected] Telephone: 46203802 Co-supervisor: Dr. Chandra Malladi Email: [email protected] Telephone: 46203813 Campus project is offered and conducted: Campbelltown Background (max 500 words) Ca2+ triggered release of neurotransmitters (i.e. regulated synaptic vesicle exocytosis) is the process underlying basic central nervous system functions such as learning and memory. This process is known to be disturbed in debilitating disease including depression, epilepsy, and schizophrenia. Understanding the essential molecular mechanisms of exocytosis is thus a rational approach to addressing such disorders. Aim of Study: Although the basic pathway leading to neurotransmitter release has been established, the current challenge is to identify components that mediate each stage [1, 2]. Using a bias-free small-molecule based approach coupled with molecular/functional analysis, our laboratory has previously identified several proteins and lipids as either critical or modulatory components [3-6]. We now aim to test the roles of these candidates utilising an in vitro neurotransmitter release assay. To this end, this project aims to: 1) Establish an in vitro synaptic vesicle exocytosis assay to monitor several stages of neurotransmitter release; and 2) utilise the developed assay to understand the specific roles of critical proteins and lipids. Methods: Synaptosomes (functional nerve terminals) and synaptic vesicles will be isolated from rat brain using established protocols, and electron microscopy will be used to verify the purity of these preparations. A time-resolved Förster resonance energy transfer (FRET) based fluorescence assay to monitor exocytosis is under development. Well established molecular assays are available in the lab to monitor global changes in protein and lipid composition, as required [7, 8]. Preliminary results have established this as a feasible approach. Ethics Application Requirements: Approval from the UWS Animal Ethics Committee is in place. Key References: 1. Becherer, U. and J. Rettig, Vesicle pools, docking, priming, and release. Cell Tissue Res, 2006. 326(2): p. 393407. 2. Rogasevskaia, T.P. and J.R. Coorssen, A new approach to the molecular analysis of docking, priming, and regulated membrane fusion. J Chem Biol, 2011. 4(3): p. 117-136. 3. Furber, K.L., D.M. Brandman, and J.R. Coorssen, Enhancement of the Ca(2+)-triggering steps of native membrane fusion via thiol-reactivity. J Chem Biol, 2009. 2(1): p. 27-37. 4. Furber, K.L., K.T. Dean, and J.R. Coorssen, Dissecting the mechanism of Ca2+-triggered membrane fusion: probing protein function using thiol reactivity. Clin Exp Pharmacol Physiol, 2010. 37(2): p. 208-217. 5. Churchward, M.A. and J.R. Coorssen, Cholesterol, regulated exocytosis and the physiological fusion machine. Biochem J, 2009. 423(1): p. 1-14. 6. Churchward, M.A., et al., Specific lipids supply critical negative spontaneous curvature--an essential component of native Ca2+-triggered membrane fusion. Biophys J, 2008. 94(10): p. 3976-3986. 7. Wright, E.P., et al., Top‐down proteomics: Enhancing 2D gel‐electrophoresis from tissue processing to high sensitivity protein detection. Proteomics, 2014. 8. Churchward, M.A., et al., Copper (II) sulfate charring for high sensitivity on-plate fluorescent detection of lipids and sterols: quantitative analyses of the composition of functional secretory vesicles. J Chem Biol, 2008. 1(1-4): p. 79-87. 137 Title of Project: Characterising the role of hSSB1 dimer formation in oxidative damage (FOR Code/s): 0601 (Biochemistry and Molecular Biology) Supervisor: Dr Liza Cubeddu Contact: [email protected] Co-supervisor: Dr Roland Gamsjaeger Contact: [email protected] Location of Project: Campbelltown Project Background Cancer is a multi-step process driven by genome instability. An effective DNA damage response is fundamental in maintaining genetic integrity and cellular survival. One major DNA damage repair pathway in humans is Base Excision Repair (BER). BER removes damaged DNA bases such as those caused by oxidative damage, a normal by-product of cellular respiration. Oxidative DNA damage, in the form of 8-oxo-Guanine (8-oxoG), is highly mutagenic, causing G-T transitions, a feature common in cancer. Single stranded DNA binding (SSB) proteins have important roles in many DNA repair mechanisms. We identified a novel human single-stranded DNA binding proteins (hSSB1) involved in initiating the repair of lethal double-stranded DNA breaks. More recently we have implicated hSSB1 in the BER response to oxidative damage. We have shown that hSSB1 is recruited rapidly to genomic DNA containing oxidised bases and that cells depleted of hSSB1 fail to repair 8oxoG damage. The main enzyme that removes and repairs of 8-oxoG bases in humans is oxo-guanine glycosylase 1 (hOgg1). We have found that hSSB1 is required for the recruitment of Ogg1 to chromatin following oxidative stress, and that the dimeric form of hSSB1 appears to be essential for this function. It is well established that some chemotherapeutic agents and radiation therapy generate reactive oxygen species in patients during cancer therapy, our molecular characterisation will pave the way to design hSSB1-based drugs that can be utilized to sensitize tumours to DNA-damaging therapies. Aim of Study: Aim 1: Design and produce hSSB1 point mutants to determine their effects on the ability of hSSB1 to dimerise. Aim 2: Determine oxidatively damaged DNA-binding ability of point mutants that abrogate dimerisation of hSSB1. Methods: Cloning and Site Directed Mutagenesis. Recombinant Protein Expression and Purification techniques. Biophysical methods to determine stoichiometry (Multi angle laser light scattering) and affinity (Biosensor) of hSSB1 monomer/dimer interactions. Ethics Application Requirements: NA Key References: Ashton NW, Bolderson E, Cubeddu L, O'Byrne KJ, Richard DJ. (2013) Human single-stranded DNA binding proteins are essential for maintaining genomic stability. BMC Molecular Biology 2013; 14(1):9 Richard DJ, Bolderson E, Cubeddu L, Wadsworth RI, Savage K, et al. (2008) Single-stranded DNA-binding protein hSSB1 is critical for genomic stability. Nature 453: 677-681 Richard DJ, Savage K, Bolderson E, Cubeddu L, So S, et al. (2011) hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex. Nucleic Acids Res 39: 1692-1702 Richard DJ, Cubeddu L, Urquhart AJ, Bain A, Bolderson E, et al. (2011) hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity. Nucleic Acids Res 39: 3643-3651 138 Title of Project: The role of the PID domain of Brd4 in the interaction with the P-TEFb transcriptional complex (FOR Code/s): 1116 (Medical Physiology), 0601 (Biochemistry and Molecular Biology) Supervisor: Dr Roland Gamsjaeger Contact: [email protected] Co-supervisor: Dr Liza Cubeddu Contact: [email protected] Location of Project: Campbelltown Project Background It is well established that chromatin, which packages eukaryotic DNA, plays an important role in transcriptional regulation. Recently, post-translational modifications on histone tails have been directly implicated with gene activation or repression. Although the role of bromodomains as effective ‘readers’ of acetylation marks on histones has been established over the last 5–10 years, accumulating evidence points to a scenario in which these proteins also have a role in other essential cellular processes. To date, the most widely studied is the involvement of the BET-family bromodomain protein Brd4 in the recruitment of P-TEFb, which regulates gene expression by enabling the elongation of transcription. The related BET bromodomain protein Brd3 has also been identified as a binding partner of P-TEFb, however, comparatively little is known about the molecular details of this interaction. Recent studies have shown that displacement of Brd4 from acetylated histones on chromatin using small molecule inhibitors is a promising new therapy for effective treatment of MLL-fusion leukaemia and pharmaceutical companies are currently aggressively pursuing Brd4 inhibitors. However, the same inhibitors that abrogate Brd4 binding show equal efficacy against Brd3. If such inhibitors are to be clinically useful, understanding, at a fundamental level, the role of Brd3 is absolutely critical for targeting specific disease states and preventing undesired off-target side effects. Aim of Study: Determine the role of the PID domain of Brd4 in the interaction with the P-TEFb complex using biophysical and structural approaches. Methods: Expression of the PID domain (Protein Interaction domain) of Brd4. Testing the interaction of the PID domain with CycT1 and Cdk9, both components of the P-TEFb complex. Structural characterisation of the PID domain and comparison with Brd3. Ethics Application Requirements: NA Key References: Dawson, M.A., Prinjha, R.K., Dittmann, A., Giotopoulos, G., Bantscheff, M., Chan, W.I., Robson, S.C., Chung, C.W., Hopf, C., Savitski, M.M. et al. (2011) Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature, 478, 529-533 Gamsjaeger, R., Webb, S.R., Lamonica, J.M., Billin, A., Blobel, G.A. and Mackay, J.P. (2011) Structural basis and specificity of acetylated transcription factor GATA1 recognition by BET family bromodomain protein Brd3. Mol Cell Biol, 31, 2632-2640 Zuber, J., Shi, J., Wang, E., Rappaport, A.R., Herrmann, H., Sison, E.A., Magoon, D., Qi, J., Blatt, K., Wunderlich, M. et al. (2011) RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature, 478, 524-528 139 Title of Project: Characterisation of functionalised chitosan films (for cell culture) (FOR Code/s): Physical Chemistry – Colloid and Surface chemistry (030603) Biochemistry and Cell Biology (0601) Macromolecular and Materials Chemistry - Physical Chemistry of Materials (030304) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Richard Wuhrer Email: [email protected] Telephone: 9089 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Location of Project: Parramatta Project Background Chitosan is an amazing polymer derived from chitin, the main component of crab or prawn shells and many others. On top of being a renewable and sustainable material, chitosan is bacteriostatic and it has thus a great potential to produce films for cells culture.[1] Our research group has developed a methodology to functionalise chitosan films with small biomolecules and quantify the grafting and these biomolecules. The surface of the film and its functionality are the key to avoid film-to-film variability in the cell culture. Scanning Electron Microscopy (SEM) allows probing the morphology of the film surface. The functionalization can be assessed through SIMS-ToF. A more in-depth analysis of the roughness is possible through Atomic Force Microscopy (AFM). All these powerful characterisation methods are available at UWS. Aim of Study: To characterise the roughness and functionalization of a chitosan film surface. Methods: SEM, SiMS ToF, AFM Ethics Application Requirements: Not applicable Key References: [1] C Gartner, BL Lopez, L Sierra, R Graf, HW Spiess, M Gaborieau, Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis and X-ray diffraction. Biomacromolecules 2011, 12, 1380. 140 Title of Project: Importance of branching and debranching in anticancer drug carriers (FOR Code/s): Biological Sciences, Analytical Biochemistry (060101) Macromolecular and Materials Chemistry - Synthesis of Materials (030306) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Prof. Jens Coorssen Email: [email protected] Telephone: 3802 Location of Project: Parramatta Project Background Poly(acrylic acid) is used in our research group to produce potential anticancer drug carriers. This polymer is smart: it reacts to pH changes thus releasing the drug in acidic media such as tumours. Large molecule such as polymers can either have a linear structure or a branched one (tree-like). We have shown that poly(acrylic acid) is branched [1] and this is beneficial to ensure that the drug does not leak out of the polymer in physiological conditions. The branched structure controls the release and retention of the drug. To understand these, the size (molar mass distribution) of the branches needs to be determined. In addition, the poly(acrylic acid) drug carrier is too large to be eliminated by the body after the drug delivery. Poly(acrylic acid) was designed to be debranched into small fragments on a longer time frame. The kinetics of debranching in physiological conditions will be investigated to ensure that the drug carrier does not accumulate for example in the kidneys. Aim of Study: To debranch a branched poly(acrylic acid) to characterise the branches and assess the potential of this poly(acrylic acid) for anticancer drug delivery. Methods: Capillary Electrophoresis, NMR spectroscopy Ethics Application Requirements: Not applicable Key References: [1] A Maniego, D Ang, Y Guillaneuf, C Lefay, D Gigmes, J Aldrich-Wright, M Gaborieau, P Castignolles, Separation of poly(acrylic acid) salts according to topology using capillary electrophoresis in the critical conditions. Analytical and Bioanalytical Chemistry 2013, 405, 9009 141 Title of Project: Using stem cell-derived lens epithelial cells to study primary and secondary cataract. (FOR Code/s): 0601, 1103, 0303, 0301 Supervisor: Dr Michael O’Connor Contact: [email protected] Location of Project: School of Medicine, Campbelltown Campus Project Background: Primary and secondary cataracts in adults, children and babies place a large burden on medical health systems worldwide. Ocular lens surgery is currently the only option to restore vision in these patients, but costs billions of dollars annually around the world. It is therefore clear that anti-cataract drug screening methods need to be developed in order to identify compounds that can inhibit or delay the formation or progression of primary and secondary cataract. Until now, development of such methods has been severely hampered by limited access to normal human lens tissue. Encouragingly, my group recently established a new method for generating pure populations of human lens epithelial cells from pluripotent stem cells. This new source of human lens cells will enable the establishment of methods for high-throughput anti-cataract drug screening. It may also enable regeneration of functional human lenses in vitro, similar to the in vitro regenerated rat lenses previously generated by my group. Such in vitro human lenses could be used for studies of lens and cataract development, toxicology studies of new drugs and cosmetics, and identification of anti-primary cataract drugs. Aim of Study: This study will give students training in key stem cell and regenerative medicine techniques specific to lens and cataract research that are also highly relevant to regenerative medicine approaches to all human tissues. Students will be encouraged to present their work at conferences and publish their findings in peer reviewed journals Methods: Students will be taught widely applicable regenerative medicine techniques including tissue culture maintenance of human pluripotent stem cells, directed differentiation to ocular lens cells, purification of lens epithelial cells, production of lens fibre cells for in vitro human lens regeneration, and application of lens epithelial cells to drug screening. Cell type characterisation will be performed by a range of techniques including flow cytometry, polymerase chain reaction, and high-content imaging. Students considering this project must be comfortable working with human embryonic stem cells before applying. Ethics Application Requirements: Appropriate ethics and biosafety approvals have been obtained for the project. Key References: 4. O’Connor and McAvoy. In vitro generation of functional lens-like structures with relevance to age-related nuclar cataract. Investigative Ophthalmology and Visual Science. 2007. 48(3):1245-52. 5. Yang et al. Efficient generation of lens progenitor cells and lentoid bodies from human embryonic stem cells in chemically defined conditions. FASEB J. 2010. 24(9):3274-83. 6. Murphy and O’Connor. A rapid, simple and efficient method for generating pure populations of lens epithelial cells from human pluripotent stem cells. In preparation. 142 Title of Project: Protein arginine methylation – a key player in cellular events (FOR Code/s): 0601 mainly (but others including 0605, 0607 and 1109 may also apply depending on project) Supervisor: Sabine C. Piller Contact: [email protected] or 46203354 Co-supervisor: TBA depending on project Contact: Location of Project: Campbelltown but some projects may involve work on other campuses including Hawkesbury, Parramatta or external as indicated below Project Background Protein arginine methylation is a post-translational modification like phosphorylation, acetylation and ubiquitination. Recent research and advances in technology have revived the initial research carried out on protein methylation in the early 1960ies (1), and protein arginine methylation has become one of the hot topics of research in a variety of fields including virology, cell biology and molecular mechanisms of disease as well as potential drug target development. Protein arginine methylation is a likely key modulator of cellular processes such as transcription, cell signalling, nuclear transport, ageing and cellular stress which has implications for a wide range of diseases including cancer, cardiovascular diseases, viral infections, lung disease and potentially neuronal diseases. Protein arginine methyltransferases (PRMTs) are a protein family that is highly conserved and can even be found in yeast (2). There are now 4 types of PRMTs known and arginine residues can be mono-methylated on the terminal nitrogen (by types, I, II and III) or on an internal nitrogen (by type IV). Arginine residues can further be modified by type I PRMTs resulting in asymmetric dimethylation of the terminal nitrogen, while type II PRMTs result in symmetric dimethylation of the terminal nitrogens. This field of research is fast moving and new findings about the mechanism and importance of protein arginine methylation are discovered and published every month. My lab has started to study protein arginine methylation initially in the HIV virus (3, 4) and work continues to clarify the role of protein arginine methylation of 2 HIV proteins. In addition, we have obtained preliminary data suggesting that arginine methylation may be important in the ageing process and may overlap with traditional Chinese herbal medicines used as anti-ageing compounds. Further, the work of one of my PhD students in 2011 has identified neuronal proteins that are methylated. We are in the process of studying the importance and role of protein arginine methylation in neurons and neuronal diseases as well as in other diseases including hepatitis, liver diseases, and cancer. Other areas of interest include studying the role of protein arginine methylation in cyanobacteria, bacteria and other microorganisms (collaborative projects with Dr Michelle Moffitt, Dr Oliver Morton, and Dr Colin Stack), in plants and mycorrhizal fungi (in collaboration with Dr Jonathan Plett at the HIE) and in ion channel forming proteins. Honours projects are available for each of the aims of the overall focus to elucidate the molecular mechanism of protein arginine methylation as listed below. Aim of Study: The major aim of the work conducted in my laboratory is to better understand protein arginine methylation and its importance in cellular pathways and disease in order to identify potential future drug targets to combat a variety of diseases. The specific aims and individual projects include: 1. Role of protein methylation in neurons and neuronal disease 2. Role of protein methylation in liver disease 3. Role of protein methylation in the regulation of cell cycle and cancer (in collaboration with Dr Qihan Dong) 4. Role of protein methylation in mycorrhizal fungi (in collaboration with Dr Jonathan Plett, HIE, Hawkesbury) 5. Role of protein methylation in microorganisms including cyanobacteria (co-supervised project with supervisor Dr Michelle Moffitt) 6. Role of protein methylation in ion channel forming proteins 7. Role of protein methylation in nuclear transport 8. Role of protein methylation in viral diseases including HIV, HCV, HBV 9. Role of protein methylation in ageing 10. Role of AdOx in protein and DNA methylation (in collaboration with Dr Patrice Castignolles, Parramatta) Methods: The major methods and techniques employed include, cell and tissue culture techniques (bacteria, yeast, eukaryotic cells), transformation, transfection, plasmid DNA preparations and purifications, PCR, site-directed mutagenesis, SDSPAGE, agarose gels, Western Blotting, immunoprecipitation, FACS studies, fluorescent confocal microscopy, and potentially some advanced microscopy techniques (FRET) ; 2D gels and mass spectrometry. Reagents and infrastructure as well as expertise with techniques is available in the Piller laboratory and from national and 143 international collaborators (including Prof Muench at SoM, Ass/Prof Roslyn London at UWA, Dr Michelle Moffitt, Dr Colin Stack, Dr Oliver Morton, Dr Patrice Castignolles, Dr Qihan Dong; SSH; Dr Jonathan Plett; HIE). Ethics Application Requirements: Most experiments are performed in cell lines and ethics approval for mouse work of primary cultured neurons is current and valid until end of 2015. Key References: 1) Paik et al. 2007 Trends in Biochemical Sciences 32(2):146-152; 2) Bedford and Clarke 2009 Molecular Cell 33: 1-13; 3) Willemsen et al. 2006 Retrovirology 3:92; 4) Mirto & Piller 2010 Future Medicine - HIV Therapy 4(1): 65. 144 Title of Project: The effect of chronic electrical stimulation on neuritogenesis. (FOR Code/s): 1109 Neurosciences 1103 Clinical sciences 060199 Biochemistry and Cell Biology not elsewhere classified 920107 Hearing, Vision, Speech and their disorders Supervisor: Dr Cherylea Browne Contact: 4620 3491 - [email protected] Co-supervisor: Dr Jennie Cederholm Contact: [email protected] Location of Project: Translational Neuroscience Facility, the University of New South Wales, and UWS Campbelltown. Project Background The events involved in transmitting sound information are crucial for us to perceive our surrounding environments. Unfortunately, there is a large population of people that suffer from hearing-related disorders, severe hearing loss or were born deaf [1]. The cochlear implant has been designed to stimulate the auditory neurons with electrical energy. The cochlear implant apparatus includes an external receiver, which receives sound information and transmits it to an external processor. The external processor transmits the electrical energy to the cochlear implant array which is positioned inside the cochlea. The signal is transmitted through the electrodes which stimulated the adjacent spiral ganglion neurons. The main issue that arises with cochlear implants is the poor electro-neural interface [2, 3]. The spiral ganglion neurites tend not to grow towards or connect to the implant array. However, it has been shown that spiral ganglion neurites can be encouraged to regenerate and grow in response to molecular therapy (e.g. neurotrophins) [4]. In addition to the efficacy of neurotrophins in restoring cochlear nerve vitality [5, 6], it is evident from several studies that electrical stimulation inherent to the cochlear implant can sustain the spiral ganglion neurons in the absence of neurotrophins [7]. Aim of Study: To determine the effect of chronic electrical stimulation on nerve cell outgrowth (neuritogenesis). Methods: The effect of chronic electrical stimulation on neuritogenesis will be assessed using an in vitro mouse spiral ganglion explant culture system we have developed at the University of New South Wales, Australia, which provides defined charge-balanced pulsed electric fields across the spiral ganglion cells (which is termed an “explant”). Spiral ganglion explants will be collected from young mice cochleae and cultured for two days in a mixture of growth factors. During this time the explant will be chronically stimulated with varying electric currents. Explants will then be processed for immunohistochemistry and will be analysed using a confocal microscope for growth and neurite extension in response to chronic stimulation. Ethics Application Requirements: Animal Ethics Approval applications will be made to the UNSW and UWS Animal Ethics Committees. Key References: 1. Mathers, C., Smith, A., & Concha, M. (2000). Global burden of hearing loss in the year 2000. Global burden of Disease, 18, 1-30. 2. Long, C. J., Holden, T. A., McClelland, G. H., Parkinson, W. S., Shelton, C., Kelsall, D. C., & Smith, Z. M. (2014). Examining the Electro-Neural Interface of Cochlear Implant Users Using Psychophysics, CT Scans, and Speech Understanding. Journal of the Association for Research in Otolaryngology, 1-12. 3. Bierer, J. A., Faulkner, K. F., & Tremblay, K. L. (2011). Identifying cochlear implant channels with poor electrodeneuron interface: electrically-evoked auditory brainstem responses measured with the partial tripolar configuration. Ear and hearing, 32(4), 436. 4. J. L. Pinyon, S. F. Tadros, K. E. Froud, A. C. Y. Wong, I. T. Tompson, E. N. Crawford, M. Ko, R. Morris, M. Klugmann, G. D. Housley, Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear. Sci. Transl. Med. 6, 233ra54 (2014). 5. Wise, A.K., et al., Effects of localized neurotrophin gene expression on spiral ganglion neuron resprouting in the deafened cochlea. Mol Ther, 2010. 18(6): p. 1111-22. 6. Yu, Q., et al., Protection of spiral ganglion neurons from degeneration using small-molecule TrkB receptor agonists. J Neurosci, 2013. 33(32): p. 13042-52. 7. Leake, P.A., G.T. Hradek, and R.L. Snyder, Chronic electrical stimulation by a cochlear implant promotes survival of spiral ganglion neurons after neonatal deafness. J Comp Neurol, 1999. 412(4): p. 543-62. 145 Title of Project: To investigate the role of SMG1 in innate immune signalling. (FOR Code/s): 060111 Signal Transduction, 110707 Innate Immunity, 111201 Cancer Cell Biology, 111206 Haematological Tumours Supervisor: Dr Tara Roberts Contact: [email protected] Co-supervisor: Dr Uda Ho (TBC) Contact: (02) 87389020 Location of Project: The Ingham Institute for Applied Medical Research. Project Background SMG1 is a member of the PI-3 kinase like kinase (PIKK) family of proteins which include ATM, DNA-PK and mTOR. Members of this family have well-characterised roles in responses to cellular stress including DNA damage and nutrient deprivation. We recently described a novel role for SMG1 as a tumour suppressor. Decreased SMG1 protein expression led to increased development of cancer, particularly lymphomas and lung adenocarcinomas. SMG1 loss also increased basal inflammation and oxidative damage to tissues prior to tumour development. These data suggest that SMG1 may contribute to cancer development, at least partially, by promoting inflammation. Aim of Study: To understand how loss of SMG1 alters innate immune responses. This study will focus on determining if and how SMG1 loss alters toll-like receptor mediated responses and inflammasome activation. Methods: This project will utilise a range of methods including mammalian cell tissue culture, siRNA knockdown, cellular activation assays (ELISA, Flow cytometry), cell signalling analysis (western blotting, immunofluorescence) as well as isolation and analysis of cells from genetically modified mice. Ethics Application Requirements: This project already has animal ethics and OGTR approval. Key References: Background to project: Roberts TL, Ho U, et al. (2013) Smg1 haploinsufficiency predisposes to tumor formation and inflammation. Proc Natl Acad Sci U S A 110(4):E285-294. Hanahan D & Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646-674. Li N, Grivennikov SI, et al. (2011) The unholy trinity: inflammation, cytokines, and STAT3 shape the cancer microenvironment. Cancer Cell 19(4):429-431. Indication of techniques: Roberts TL, Dunn JA, et al. (2011) The immunostimulatory activity of phosphorothioate CpG oligonucleotides is affected by distal sequence changes. Mol Immunol 48(8):1027-1034. Roberts TL, Idris A, et al. (2009) HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science 323(5917):1057-1060. 146 Ecology 147 Field of Research: Ecology/Molecular Biology/Immunology Title of Project: Wombat mange Supervisor: Dr Julie Old Email:[email protected] Co-supervisor: Dr Lauren Young Email:[email protected] Campus project is offered and conducted: HWK Telephone: x1283 Telephone: NA Background (max 500 words) Wombats suffer from sarcoptic mange, a debilitating disease that eventually leads to their death. This project will incorporate field (habitat surveys and spotlighting) and laboratory skills (molecular biology) to investigate the role of mange in wombat populations. Several more specific projects are available in this area. Aim of Study: Investigate mange in wombats using laboratory and/or field skills. Methods: The projects involves field and/or molecular biology skills. Ethics Application Requirements: Ethics, biosafety and NSW NPWS licences have been granted. Risk assessments will be required. Key References: 148 Field of Research: Biochemistry/Microbiology/Immunology Title of Project: Lipid profiles in marsupial pouches over the different reproductive stages Supervisor: Dr Julie Old Email:[email protected] Telephone: x1283 Co-supervisor: Dr Jo-Anne Chuck Email:[email protected] Telephone: x9906 Campus project is offered and conducted: HWK/PTA Background (max 500 words) Marsupials are born without functional immune tissues and are therefore unable to mount specific immune responses. Despite this, marsupial neonates survive in the microbial-rich pouch. Recently, peptides have been identified in marsupial pouches at the time of oestrus with antimicrobial properties. Lipids secreted by the pouch skin of marsupials may also have antimicrobial properties, and play a role in innate immunity of young marsupials. The project can be adapted to allow to suit a chemistry, microbiology, biochemistry, or immunology student. Aim of Study: The project will identify lipids in the pouches of tammar wallabies (Macropus eugenii) during the different reproductive stages to determine if they may play a role in immunological protection of the neonatal marsupial. Methods: It is a laboratory-based biochemistry/immunology project, however some animal handling experience can be incorporated. Ethics Application Requirements: Risk assessments will be required. All other requirements are in place. Key References: Old J, Deane E (2000) Development of the immune system and immunological protection in marsupial pouch young. Dev Comp Immunol. 24, 445-454. ISSN 0145-305X 149 Field of Research: Molecular Biology/Immunology/Developmental Biology Title of Project: Marsupial immunology Supervisor: Dr Julie Old Email:[email protected] Co-supervisor: Dr Lauren Young Email:[email protected] Campus project is offered and conducted: HWK Telephone: x1283 Telephone:NA Background (max 500 words) Various projects are available in the area of marsupial immunology. Very little is known about Dasyurid marsupials (carnivorous marsupials), including their immunology, with many species in the Family listed as endangered or threatened. One of the key immunological questions in marsupials involves understanding how newborn marsupials survive the microbial onslaught in the pouch when they lack mature immune tissues and are therefore unable to mount their own immune response to pathogens. Aim of Study: The project aims to isolate the cDNA sequences for key immunological molecules using molecular techniques in the phascogale (Phascogale calura) and/or other Dasyurid species with the aim of increasing the understanding of the development and in the longer term function of their immune system. Once isolated the expression levels of these molecules will be determined using qPCR. Methods: The project involves molecular laboratory work as well as a small animal handling component with the animals housed on campus. Ethics Application Requirements: Ethics, biosafety and NSW NPWS licences have been granted. Risk assessments will be required. Key References: Old J, Deane E (2000) Development of the immune system and immunological protection in marsupial pouch young. Dev Comp Immunol. 24, 445-454. ISSN 0145-305X Belov K, Miller RD, Old JM, Young LJ (2013). Marsupial Immunology Bounding Ahead. Australian Journal of Zoology. 61, 24-40. ISSN 0004-959X 150 Field of Research: 060208 Terrestrial Ecology Title of Project: Ecological restoration of the Cumberland Plain Woodland: Is local always best? Supervisor: Paul Rymer Email: [email protected] Co-supervisor: Email: Campus project is offered and conducted: HWK Telephone: 02 4570 1094 Telephone: Background (max 500 words) Aim of Study: The Cumberland Plain Woodland (CPW) is listed as a critically endangered ecological community. It has experienced extensive habitat loss and fragmentation through agricultural and urban development; as such the small remnants are at increased risk of extinction. Ecological restoration aims to restore degraded sites through removal of weeds and reestablishment of native species. Best practise maintains local provenances to reduce mixing of gene pools that may be locally adapted to different sites. This, however, imposes a significant constraint on seed collectors which in the context of highly fragmented landscapes limits the amount and genetic diversity of seed for restoration. This project will explore the relative importance of local adaptation and genetic diversity for successful ecological restoration. Students will work in collaboration with Greening Australia to develop a project with applied outcomes for ecological restoration. This project will develop students’ field, glasshouse and laboratory skills, along with their analytical and writing skills. Methods: Seed set and viability, temperature response of seed germination and plant growth, and plant stress response (optional chromosome counts and genome size estimation). Ethics Application Requirements: No Key References: Rymer PD, Sandiford M, Harris SA, Billingham MR, Boshier DH (2013) Remnant Pachira quinata pasture trees have greater opportunities to self and suffer reduced reproduction due to inbreeding depression. Heredity. [JIF 4.110] P.D. Rymer, R.J. Whelan, D.J. Ayre, P.H. Weston, K.G. Russell (2005). Reproductive success and pollinator effectiveness differ in common and rare Persoonia species (Proteaceae). Biological Conservation, 123, 521-532. [Cited 28, JIF 3.794] Hancock, N. & Hughes, L. (2012) How far is it to your local? A survey on local provenance use in New South Wales. Ecological Management and Restoration, 13, 259-266. Hancock, N., Leishman, M.R. & Hughes, L. (in press) Testing the "local provenance" paradigm: a common garden experiment in Cumberland Plain Woodland, Sydney, Australia. Restoration Ecology, Early View, Article first published online: 17 Oct 2012. doi:10.111/j.1526-100X.2012.00931.x. Paul Gibson-Roy, Greg Moore, John Delpratt and Jess Gardner (2010) Expanding horizons for herbaceous ecosystem restoration: the Grassy Groundcover Restoration Project. Ecological Management & Restoration. Volume 11, Issue 3, pages 176–186 151 Field of Research: 060208 Terrestrial Ecology Title of Project: How do plant-insect interactions behave along steep environmental gradients? Supervisor: Paul Rymer Email: [email protected] Co-supervisor: James Cook Email: [email protected] Campus project is offered and conducted: HWK Telephone: 02 4570 1094 Telephone: 02 4570 1371 Background (max 500 words) Aim of Study: Many plant-insect associations have evolved over millions of years; however some interactions have emerged more recently with environmental change. This can break up key mutualistic interactions (such as pollination) and antagonistic interactions (such as seed predation) with the loss and emergence of different species in the landscape. Critically, the disruption of plant-insect associations can threaten the viability of natural populations, alter species distributions, and result in a loss of biodiversity. This project will explore plant-insect interactions along a steep altitudinal gradient from coastal Sydney to upland Blue Mountains. It will focus on insects associated with legumes (including Acacia, Dillwynia, Pultenaea) within established plots in the Biological Adaptation Transect Sydney. Students will be engaged in fieldwork to sample insects during plant flowering and seed set, insect identification with morphology (and potentially DNA barcoding), followed by ecological and evolutionary analyses to deduce the stability / variability of plant-insect interactions with changing climate. Methods: Fieldwork to sample insects from Sydney to the Blue Mountains, insect identification via morphology (and potentially DNA barcoding), and ecological and evolutionary analyses Ethics Application Requirements: No Key References: Rymer PD, Sandiford M, Harris SA, Billingham MR, Boshier DH (2013) Remnant Pachira quinata pasture trees have greater opportunities to self and suffer reduced reproduction due to inbreeding depression. Heredity. [JIF 4.110] Rymer PD, Johnson SD, Savolainen V (2010). Pollinator behaviour and plant speciation: can assortative mating and disruptive selection maintain distinct floral morphs in sympatry? New Phytologist 188(2): 426-436. [Cited 4, JIF 6.736] P.D. Rymer, R.J. Whelan, D.J. Ayre, P.H. Weston, K.G. Russell (2005). Reproductive success and pollinator effectiveness differ in common and rare Persoonia species (Proteaceae). Biological Conservation, 123, 521-532. [Cited 28, JIF 3.794] Segar ST, Pereira RAS, Compton SG, Cook JM, (2013) 'Convergent structure of multitrophic communities over three continents', Ecology Letters, vol.16, no.12, pp 1436-1445 Al-Beidh S, Dunn DW, Power SA, Cook JM, (2012) 'Parasites and mutualism function: Measuring enemy-free space in a fig-pollinator symbiosis', Oikos, vol.121, no.11, pp 1833-1839 Oliver TH, Leather SR, Cook JM, (2012) 'Ant larval demand reduces aphid colony growth rates in an ant-aphid interaction', Insects, vol.3, no.1, pp 120-130 152 Title of Project: Behavioural impacts of ocean acidification: are cuttlefish resilient? (FOR Code/s): 0602 Supervisor: Professor Pauline Ross Contact: [email protected] Co-supervisor: Dr Laura Parker Contact: [email protected] Location of Project: Sydney Institute of marine Science (SIMS) Mosman Project Background Ocean acidification, caused by the increased absorption of anthropogenic atmospheric carbon dioxide (CO2) emissions by the ocean, is occurring at an alarming rate. Current emissions scenarios suggests that by the end of this century the pH of the surface oceans will have dropped by an average of 0.3-0.5 pH units compared to present day levels. Understanding how this change in ocean chemistry will impact on marine organisms is critical to making predictions of the future fate of marine ecosystems. Over the last decade, numerous studies have documented negative impacts of ocean acidification on the physiology and development of marine species. These impacts include alterations in acidbase status and metabolic rate, reductions in growth and calcification, immune response, reproduction, fertilisation, larval development, settlement and survival. More recently, however, a handful of studies have suggested that ocean acidification may also have negative impacts on the behaviour or marine organisms. In fish for example, exposure to ocean acidification has been shown to cause an increase in boldness and activity, altered auditory preferences, impaired olfactory function and a loss of behavioural lateralization. Further, in the only study to look at the behavioural response of a marine mollusc, exposure to ocean acidification reduced the ability of a gastropod conch snail to decide to escape from a predator. Whether ocean acidification will impact on the behaviour of other marine organisms and how their behaviour will be impacted remains largely unknown. Cuttlefish are cephalopod molluscs which have a high capacity to regulate ion and acid-base status. As a result of this, unlike other mollusc species, cuttlefish have shown an inbuilt resilience to the impacts of ocean acidification. Previous studies looking at the impact of ocean acidification on the physiology and development of cuttlefish species have found neutral and sometimes even positive effects. But the impacts of ocean acidification on the behavioural patterns of cuttlefish are yet to be considered. Cuttlefish are among the most intelligent marine invertebrate species and as such they display highly developed behavioural patterns. Aim of Study: This study will measure whether the behavioural response of an Australian cuttlefish species is altered during prolonged exposure to ocean acidification. Methods: This project will use state of the art aquarium facilities at SIMS which has controlled CO2 and temperature rooms. Ethics Application Requirements: Nil Key References: Parker, L.M.; Ross, P.M.; O’Connor, W.A.; Borysko, L.; Raftos, D.A.; Pörtner, H.O. Adult exposure influences offspring response to ocean acidification in oysters. Glob. Change Biol. 2012, 18, 82–92. Gutowska, M.A.; Pörtner, H.O.; Melzner, F. Growth and calcification in the cephalopod Sepia officinalis under elevated seawater pCO2. Mar. Ecol. Prog. Ser. 2008, 373, 303–309. Gutowska, M.A.; Melzner, F.; Pörtner, H.O.; Meier, S. Cuttlebone calcification increases during exposure to elevated seawater pCO2 in the cephalopod Sepia officinalis. Mar. Biol. 2010, 157, 1653–1663. 153 Title of Project: Restoration of oyster reefs in eutrophic estuaries (FOR Code/s): 0602 Supervisor: Professor Pauline Ross Contact: [email protected] Co-supervisor: Drs Laura Parker and Victoria Cole Contact: [email protected]; [email protected] Location of Project: Office of Environment and Heritage (OEH), Lidcombe Declining water quality, including eutrophication, has been identified as a major coastal issue. Excess nutrients result from activities within the catchment, e.g. runoff from agricultural areas and urban stormwater. The over-abundance of nutrients increase phytoplankton blooms which cause decreases in biodiversity and adverse impacts on human health. Oysters have an important role in estuaries by improving water quality in terms of reducing suspended solids, phytoplankton blooms and organic carbon. Increasing oysters has been proposed as a management strategy to improve water quality in eutrophic estuaries, and has been shown to be highly successful overseas. Aim of Study: This project aims to determine the usefulness of oysters in the management of nutrient-rich urban waterways. We aim to develop a predictive tool that links eutrophication risk with the abundance and filtration capacity of oysters. Furthermore, these findings will be linked to the enhancement of coastal biodiversity through restoration of oyster reefs. Methods: This project will make use of novel field methods, historical data and risk assessment models to determine the effectiveness of bivalves in mediating urban waterways. Using the Coastal Eutrophication Risk Assessment Tool (CERAT) developed by the NSW Office of Environment and Heritage (OEH), available online free through the OZCoasts website, estuaries with range of eutrophication risks along the NSW coast will be selected. The estuaries will be of a similar size but range from highly eutrophic to completely pristine. In each of the 5 estuaries, which have oysters, the abundance of oysters will be determined from surveys. In each estuary, a hierarchically nested sampling design will be used, in which 10 locations, each with 2 sites, and 6 replicate 50 x 50 cm quadrats will be sampled. Each of the small patches will be destructively sampled. Oysters and associated fauna will be preserved in 70% ethanol for processing in the laboratory. For each sample, the size (shell height and shell length) of each oyster will be measured. The mass of dried oyster flesh will be also determined by scooping out each oyster from the shell and drying it in at 50°C oven for 24 hours or until constant weight using an electric balance is achieved. From each of these samples, the associated biodiversity will determined. All macrofauna, retained on a 500µm will be identified to species and enumerated. Ethics Application Requirements: Nil Key References: Coen, L. D., R. D. Brumbaugh, D. Bushek, R. Grizzle, M. W. Luckenbach, M. H. Posey, S. P. Powers, and S. G. Tolley. 2007. Ecosystem services related to oyster restoration. Marine Ecology-Progress Series 341:303-307. Cole, V. J. and C. D. McQuaid. 2010. Bioengineers and their associated fauna respond differently to the effects of biogeography and upwelling. Ecology 91:3549-3562. Grabowski, J. H., A. R. Hughes, D. L. Kimbro, and M. A. Dolan. 2005. How habitat setting influences restored oyster reef communities. Ecology 86:1926-1935. Grabowski, J. H. and C. H. Peterson. 2007. Restoring oyster reefs to recover ecosystem services. Pages 281-294 in K. Cuddington, J. E. Beyers, A. Hastings, and W. G. Wilson, editors. Ecosystem Engineers. Elsevier, Oxford 154 Title of Project: Microplastics in the marine environment (FOR Code/s): 0602 Supervisor: Professor Pauline Ross Contact: [email protected] Co-supervisor: Drs Laura Parker and Victoria Cole Contact: [email protected]; [email protected] Location of Project: Sydney Institute of Marine Science (SIMS) Mosman Plastic pollution is a major global issue. In marine environments “microplastics” which are small plastic particles, less than five hundred micrometers, result from the degradation of large plastic, exfoliants in face creams and shedding of synthetic fibres during domestic clothes washing. Microplastics can be found in the sediment and water column being e abundant in urban waterways. Once in the marine environment, they are small enough to be filtered by numerous marine filter feeding organisms, where they have been found to enter the digestive and circulatory system. Already preliminary observations have found microplastic pollution in the sediment of Parramatta River, Sydney Harbour. Microplastics have also been found circulating in the haemolymph of ecologically and economically significant filter feeding organisms such Sydney rock oyster, Saccostrea glomerata. Aim of Study: This study will determine the level of microplastic ingestion of a wide variety of marine organisms using carboxylatemodified polystyrene latex beads. It will also determine the potential impact on organism health due to the toxic materials which attach to microplastics. Ethics Application Requirements: Nil Key References: Browne, M, Dissanayake, A, Galloway, TS, Lowe, DM and Thompson, RC 2008, Ingested microscopic plastic translocates to the circulatory system of the mussel, Mytilus edulis (L), Envrionmental Science Technology, vol. 42, no. 13, pp. 5026-5031. Thompson, R, Olsen, Y, Mitchell, P, Davis, A, Rowland, S, John, A, McGonigle, D, Russell, A 2004, Lost at Sea, Where is all the plastic?, Science, vol. 304, no. 5672, pp. 838. Thompson, R, Moore, F, Vom Saal, F and Swan S 2009, Plastics, the environment and human health: current consensus and future trends, Philosophical Transactions of the Royal Society B: Biological Sciences, vol. 364, no. 1526, pp. 2153–2166. 155 Title of Project: Turtle Conservation Team: Optimising Management to Address Turtle Declines (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Turtles are evolutionary survivors. Their hard protective shell and longevity has allowed them to survive 220 million years of natural selective pressures. But the combination of rapid, human-induced, changes (invasive species, harvesting and river regulation) has led to nearly half of all turtle fauna either endangered or extinct in the wild and without strategic intervention, much of the turtle lineage will be extinct by the end of the 21st century. Besides their conservation value as an iconic native vertebrate, the rapid decline of freshwater turtles may have far greater implications for the entire ecosystem, because their biomass is a similar magnitude to fis, and their role in the food chain is likely to be complex and diverse, yet completely unknown. Given their longevity, however, anthropogenic changes to the River ecosystem through the introduction of invasive species and changes in water management may only now be manifesting into population declines and local extinctions. This project will team with management agencies throughout the Murray River to identify and address threats to freshwater turtles, which are endangered in many states of Australia. The project will determine predation rates on turtle nests and nesting females, trial new fox management options, and assess turtle nesting preferences. TurtleSAT (TurtleSAT.org.au) will be used in this project, which will allow GIS spatial analysis to develop broad-scale predictive maps of turtle and fox ‘hotspots’ throughout the Murray River. You will be part of a large team of researchers, including post-docs and PhD students. You will have the opportunity to work closely with researchers from the University of Sydney, University of NSW and University of Canberra, as well as management agencies from three states. Animal Ethics approval is required. 156 Title of Project: Turtle Conservation Team: Impact of Dams on Turtle Movement and Recruitment (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Turtles are evolutionary survivors. Their hard protective shell and longevity has allowed them to survive 220 million years of natural selective pressures. But the combination of rapid, human-induced, changes (invasive species, harvesting and river regulation) has led to nearly half of all turtle fauna either endangered or extinct in the wild and without strategic intervention, much of the turtle lineage will be extinct by the end of the 21st century. Besides their conservation value as an iconic native vertebrate, the rapid decline of freshwater turtles may have far greater implications for the entire ecosystem, because their biomass is a similar magnitude to fis, and their role in the food chain is likely to be complex and diverse, yet completely unknown. Given their longevity, however, anthropogenic changes to the River ecosystem through the introduction of invasive species and changes in water management may only now be manifesting into population declines and local extinctions. Many river and wetland systems are fragmented by dams and altered ecologically through flow regulation, increasing the likelihood of population isolation for many aquatic species. Hence knowledge about the distribution and connectivity of species across important ecosystems, like the Murray-Darling Basin, both at the population and genetic levels, is essential if we are to manage them properly. Distinct metapopulations may exist between dams, as well as, in billabongs that are disconnected from the river except during major floods. If dispersal regularly occurs from certain key sites within these metapopulations, gene frequencies may be homogenised and local adaptation to fox predation may be reduced. Radiotracking (Telemetry) and molecular nuclear markers will be used to provide estimates of gene flow between populations to assess impact altering flow and connectivity. You will be part of a large team of researchers, including post-docs and PhD students. You will have the opportunity to work closely with researchers from the University of Sydney, University of NSW and University of Canberra, as well as management agencies from three states. Animal approval is required. 157 Title of Project: Turtle Conservation Team: Turtle Nest Adaptations (FOR Code/s): Ecology and Evolution (Group in 0602, 0603 and 0608) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Over the last 3 years, our group have discovered some amazing adaptations that embryos, hatchlings and even mothers use to improve survival of eggs in the nest. This project will focus on turtle emergence from the nest and what drives some turtles to over-winter in the nest for up to 9-12 months, surviving only on yolk provided in the egg. You will use military technology to find turtle nests and hatchlings underground. Laboratory experiments will run parrallel with field tests. Animal approval is required. 158 Title of Project: Power of Citizen Science: Using WomSAT to Manage Wombat Road Mortalities (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Australia Wide Project Background WomSAT is a new community mapping tool to that employs citizen science to determine the location of wombats throughout Australia. Many of these sightings are of road mortalities. This project will employ WomSAT and advanced GIS mapping techniques to determine hotspots of mortality. Important habitat data at these hotspots will be collected to determine if consistent patterns exist, which will allow harm mitigation strategies to be implemented. The project will also explore the social aspects of citizen science and promote WomSAT among management groups. Human Ethics approval may be required. 159 Title of Project: Impact of Domestic Cats on Native Wildlife in Urban Fringes (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Blue Mountains Project Background This project will evaluate the impact of cats on native wildlife in the Blue Mountains. The project will specifically target domestic cats and their owners to determine perception versus reality of domestic cat impacts. We will employ new control devices that spray liquids on cats as they investigate lures. The liquid can deliver a toxin, but in this project will spray domestic cats with coloured dyes- the colour will depend how far into the bush the cat has wandered. Owners will be encouraged to report the colour on the cat and their location through a website/app. The project will work very closely with environmental officers from Blue Mountains City Council. Animal and Human Ethics approval is required. 160 Title of Project: Turtle Conservation Team: Ecological Function of Turtles (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Turtles are evolutionary survivors. Their hard protective shell and longevity has allowed them to survive 220 million years of natural selective pressures. But the combination of rapid, human-induced, changes (invasive species, harvesting and river regulation) has led to nearly half of all turtle fauna either endangered or extinct in the wild and without strategic intervention, much of the turtle lineage will be extinct by the end of the 21st century. Besides their conservation value as an iconic native vertebrate, the rapid decline of freshwater turtles may have far greater implications for the entire ecosystem, because their biomass is a similar magnitude to fis, and their role in the food chain is likely to be complex and diverse, yet completely unknown. Given their longevity, however, anthropogenic changes to the River ecosystem through the introduction of invasive species and changes in water management may only now be manifesting into population declines and local extinctions. The project will develop complex food webs in a range of habitats throughout eastern Australia. We will also manipulate turtle composition and abundance in experimental wetlands on the Hawkesbury campus and evaluate changes in food web dynamics and the relative importance of turtles on ecosystem function. The project will implement a large-scale experimental flood into Hawkesbury wetlands to evaluate the importance of regular inundations for food web dynamics and particular species of turtle. You will be part of a large team of researchers, including post-docs and PhD students. You will have the opportunity to work closely with researchers from the University of Sydney, University of NSW and University of Canberra, as well as management agencies from three states. Animal Ethics approval is required. 161 Evolutionary Biology 162 Title of Project: Turtle Conservation Team: Turtle Nest Adaptations (FOR Code/s): Ecology and Evolution (Group in 0602, 0603 and 0608) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Over the last 3 years, our group have discovered some amazing adaptations that embryos, hatchlings and even mothers use to improve survival of eggs in the nest. This project will focus on turtle emergence from the nest and what drives some turtles to over-winter in the nest for up to 9-12 months, surviving only on yolk provided in the egg. You will use military technology to find turtle nests and hatchlings underground. Laboratory experiments will run parrallel with field tests. Animal approval is required. 163 Field of Research: 060303 Biological Adaptation Title of Project: Climate change impacts on different plant functional groups along a steep natural environmental gradient Supervisor: Paul Rymer Email: [email protected] Telephone: 02 4570 1094 Co-supervisor: David Tissue Email: [email protected] Telephone: 02 4570 1853 Campus project is offered and conducted: HWK Background (max 500 words) Aim of Study: Acknowledging that the impacts of climate change will vary both by region and plant type, we aim to identify gene pools within natural populations of plants, representing different functional groups, along a steep environmental gradient. In particular, we are interested in assessing the capacity of these different functional groups to adapt to future climate conditions. We will assess natural populations from eastern Australia, ranging in environment from subtropical coastal to cold upland areas, among a range of plant functional groups (e.g. C3 & C4 grasses, herbs, seeders, resprouters, and trees). Importantly this gradient traverses several IBRA bioregions that encompass striking differences in key climatic variables (temperature and rainfall), which are predicted to change in future climate scenarios. Molecular, ecological and physiological approaches will be undertaken to characterise plant and ecosystem capacity to respond to changing climate conditions. A combination of field, glasshouse and laboratory experiments will determine (1) genetic connectivity among populations and bioregions, (2) seedling establishment, growth, and physiological response to abiotic and biotic conditions, and (3) gene expression and sequence variation linked to differential response among bioregions and functional groups. We aim to identify gene pools with adaptive capacity and geographic areas suitable for the successful establishment of plantations and ecosystem function. In addition, these quantitative parameters of dispersal, plasticity and adaptation will be incorporated into mechanistic models to estimate the fundamental niche under current and future climate conditions. Students will be encouraged to develop field, glasshouse, and/or laboratory components to provide them with a broad training and understanding of the ecological and evolutionary patterns and processes in the system. There will be ample opportunity for students to direct their research towards ecological, physiological and/or population genetic areas of investigation. Students will also have the scope to focus on specific functional or taxonomic groups. Collaborating institutions: Botanic Gardens Trust, National Parkes & Wildlife Services, Greening Australia, CSIRO Methods: Experimental manipulations, plant growth, trait measurements, physiology and/or molecular analyses. Statistics and writing. Ethics Application Requirements: No Key References: Rymer PD, Dick CW, Vendramin GG, Buonamici A, Boshier D (2013) Recent phylogeographic structure in a widespread ‘weedy’ Neotropical tree species, Cordia alliodora (Boraginaceae). Journal of Biogeography. [Cited 2, JIF 4.863] Rymer PD, Manning JC, Goldblatt P, Powell MP, Savolainen V (2010). Evidence of recent and continuous speciation in a biodiversity hotspot: a population genetic approach in southern African gladioli (Gladiolus; Iridaceae). Molecular Ecology 19(21): 4765-4782. [Cited 10, JIF 6.275] Duan H, Amthor JS, Duursma RA, O'Grady AP, Choat B, Tissue DT, (2013) 'Carbon dynamics of eucalypt seedlings exposed to progressive drought in elevated [CO2] and elevated temperature', Tree Physiology, vol.33, no.8, pp 779792 Mitchell PJ, O'Grady AP, Tissue DT, White DA, Ottenschlaeger ML, Pinkard EA (2013) 'Drought response strategies define the relative contributions of hydraulic dysfunction and carbohydrate depletion during tree mortality', New Phytologist, vol.197, no.3, pp 862-872 164 Genetics 165 Title of Project: Investigating the association between altered cholesterol and fat metabolism, and redox (antioxidant) balance and free radical accumulation/damage in cells. (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact:[email protected] Co-supervisor: Contact: Location of Project:Campbelltown campus Project Background Maintenance of an optimal redox environment in cells (i.e. reducing/oxidising) is critical for functioning of many cellular processes and for protecting cells against the damaging effects of reactive oxygen species (ROS). Cells are continually exposed to reactive oxygen species (ROS or free radicals) as part of normal metabolism. These ROS are toxic, affect redox balance, and have been implicated in many diseases including cancer, cardiovascular disease and arthritis. Key cellular systems (e.g. glutathione) maintain redox balance. Lipid metabolism and maintenance of an optimal redox environment are intimately linked through their requirement for NADPH as a cofactor. Substantial NADPH supplies are consumed in maintaining redox (antioxidant) systems as well as in the synthesis of lipids e.g. sterols (ergosterol/cholesterol) and fatty acids. Equally synthesis of sterols consumes appreciable levels of oxygen, and membrane sterol composition modulates oxygen diffusion. Sterols therefore may function in protecting of cells against oxygen or more specifically ROS (i.e. free radicals). Altered lipid metabolism, redox balance and/or ROS accumulation are associated with many diseases including, diabetes and neurodegenerative diseases including Alzheimer’s and Parkinson’s. Surprisingly an in depth understanding of how abnormal lipid metabolism affects redox/antioxidant defences, and detoxification of ROS has not been thoroughly investigated. Conversely how changes in redox/ROS affect lipid metabolism has not been studied in detail. Aim of Study: This project will study how the DNA synthesis and repair mechanisms of cells is impacted by changes in redox balance. The project also aims to study the converse, that is how changes in DNA homeostasis affect a cells ability to maintain redox balance and detoxification of reactive oxygen species. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) to study the extent to which lipid metabolic pathways, redox homeostasis and ROS production are inter-connected. These resources include novel redox sensing probes based on green fluorescent protein (roGFP) that can selectively measure dynamic changes in redox balance in real-time in live cells. Production of free radical species will also be measured. This project will use a range of instrumentation and techniques including flow cytometry, fluorescence microscopy and assays detecting DNA damage. The project will also exploit the vast resources of genome-wide deletion/overexpression strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, as well as gene libraries that allow researchers to selectively overexpress most genes in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to test almost any hypotheses. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 166 Title of Project: Investigating the link between DNA synthesis/repair, redox balance and production of free radicals (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact:[email protected] Co-supervisor: Contact: Location of Project:Campbelltown campus Project Background Maintenance of an optimal redox environment in cells (i.e. reducing/oxidising) is critical for functioning of many cellular processes and for protecting cells against the damaging effects of certain free radical species. Cells are equipped with key systems (e.g. glutathione) that maintain redox balance. Altered redox balance is associated with many diseases including, cancer, diabetes, neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases, and has been implicated as an important factor regulating cell growth and ageing. Cells of are continually exposed to reactive oxygen species (ROS or free radicals) as part of normal metabolism. These ROS are toxic, affect redox balance, and have been implicated in many diseases including cancer, cardiovascular disease, arthritis and those listed above. Altered lipid metabolism has also been associated with many of the above diseases. Maintenance and repair of DNA and maintenance of an optimal redox environment are closely linked through their requirement for NADPH as a cofactor. NADPH is used in the synthesis of DNA but is also used to keep redox/protective systems in balance. Combined treatments of cells with agents that affect redox systems in conjunction with DNA damaging agents has shown strong efficacy in treatment of some cancers. Surprisingly there an in depth understanding of how changes in DNA metabolism affect the ability of cells to maintain their redox environment and vice-versa is lacking. Aims: This project will study how the DNA synthesis and repair mechanisms of cells is impacted by changes in redox balance. The project also aims to study the converse, that is how changes in DNA homeostasis affect a cells ability to maintain redox balance and detoxification of reactive oxygen species. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) to study the extent to which lipid metabolic pathways, redox homeostasis and ROS production are inter-connected. These resources include novel redox sensing probes based on green fluorescent protein (roGFP) that can selectively measure dynamic changes in redox balance in real-time in live cells. Production of free radical species will also be measured. This project will use a range of instrumentation and techniques including flow cytometry, fluorescence microscopy and assays detecting DNA damage. The project will also exploit the vast resources of genome-wide deletion/overexpression strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, as well as gene libraries that allow researchers to selectively overexpress most genes in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to test almost any hypotheses. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 167 Title of Project: The interaction between mitochondrial function and sphingolipid metabolism. Implications for programmed cell death and human diseases. (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact:[email protected] Co-supervisor: Contact: Location of Project:Campbelltown campus Project Background Sphingolipids play key roles in a broad range of cellular processes including: the formation of lipid micro domains “rafts” in membrane bilayers, that influence protein sorting and signal transduction; signaling molecules in cell differentiation, growth and cell cycle progress/arrest, cholesterol metabolism and stress signaling; and immune function, endocytosis and programmed cell death. Due to the role of sphingolipids in important cellular processes the impact of altered sphingolipid metabolism can have very serious consequences for cells. Altered sphingolipid metabolism has also been shown to play an important role in the pathobiology of diseases including: cancer, diabetes and metabolic syndrome; heart disease; Alzheimer’s disease; Niemann-Pick; and immune dysfunction. In some cancers altered sphingolipid homestasis appears to play a key role in disease progression. Crucially, despite the role of sphingolipids in a diverse range of serious human diseases, on a global or a “systems-wide” level very little is known of how the broad array of cellular functions influence sphingolipid homeostasis and/or vice-versa. Recently we have identified novel links between mitochondrial function and sphingolipid metabolism. This is a two bidirectional effect whereby altered mitochondrial function impacts on sphingolipid metabolism, and conversely, we have identified cases were altered sphingolipid metabolism disrupts mitochondrial respiration. Aims: To investigate how mitochondrial dysfunction (e.g. respiratory ) leads to abnormal sphingolipid homeostasis, and, vice-versa how defects in sphingolipid metabolism impact mitochondrial function, including respiratory capacity. This study also aims to identify on a genome-wide level how the various process conducted in cells affects sphingolipid metabolism. The findings will help us to better understand the factors that contribute to abnormal sphingolipid metabolism and inform our understanding of diseases (e.g. metabolic syndrome, cancer, neurodegenerative diseases) where altered sphingolipid metabolism has been implicated. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) as well as leading edge techniques and resources. The project will exploit the genome-wide deletion strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, lipid analyses, as well as suite of powerful yeast strain libraries that allow us to selectively manipulate almost all genes (deletion or overexpression) in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to readily test most hypotheses. This project will utilise sophisticated analytical methodology including flow cytometry, mass spectrometry and fluorescent microscopy If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 168 Title of Project: Understanding why depleting the key antioxidant, glutathione, leads to catastrophic loss of mitochondrial DNA in cells. (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact: [email protected] Co-supervisor: Contact: Location of Project: Campbelltown campus Project Background Glutathione is an essential molecule that acts as a key redox buffer, antioxidant and protectant against toxins such as heavy metals and drugs. Decreased cellular levels of GSH in cells leads to a range of detrimental effects including increased accumulation of free radicals and cellular damage, defects in protein folding and severe disturbance of iron metabolism. Glutathione is non to decrease during the ageing process and GSH depletion has been linked with numerous disease process including Alzheimer’s disease, Parkinson’s disease, diabetes, and alcoholic liver disease. In the latter case depletion of mitochondrial glutathione has been implicated in the disease process. Glutathione depletion is also known to occur as part of the natural ageing process by also can be caused acutely through exposure to many toxins including heavy metals, poisons and medications (e.g. paracetamol). We have recently demonstrated that GSH depletion in yeast leads to a catastrophic and complete loss of the mitochondrial DNA from cells (mtDNA). Loss of mDNA was found to correlate with iron overload in mitochondria, a burst of reactive oxygen species (ROS) production. While we have some key pieces of the puzzle, it is still unclear what the precise mechanisms underlying mtDNA loss are. Since damage or loss of mtDNA poses serious implications for human health and disease the significance of understanding the mechanism(s) involved are anticipated to be far reaching. Aims: This project will aim to elucidate how the mechanisms through which glutathione depletion affects mtDNA integrity. The project will also aim to study mitochondrial glutathione homeostasis using high through put flow cytometry and novel in vivo redox probes based on roGFP (redox GFP). Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast), including genome-wide collections of strains that either have a gene deleted or conversely overexpressed. The project will involve the use of highly sophisticated flow cytometry methods to analyse mtDNA loss, mitochondrial energization, mitochondrial redox and ROS production. These resources used will include novel redox sensing probes based on green fluorescent protein (roGFP) that can selectively measure dynamic changes in redox balance in mitochondria in real-time. Production of free radical species will also be measured using fluorescent dyes. This project will use a range of instrumentation and techniques including flow cytometry, fluorescence microscopy and assays detecting mitochondrial DNA damage. The project will also exploit the vast resources of genome-wide deletion/overexpression strain collections, drug treatments, a range of recombinant DNA biochemical assays, as well as gene libraries that allow researchers to selectively overexpress most genes in the yeast genome. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 169 Field of Research: 060411 Population, Ecological and Evolutionary Genetics Title of Project: Contrasting the population genetic structure of Eucalypts with continuous and disjunct distributions: Implications for plant adaptation to climate change Supervisor: Dr Paul Rymer Email: [email protected] Telephone: 4570 1094 Co-supervisor: Email: Telephone: Campus project is offered and conducted: HWK Background (max 500 words) Aim of Study: Genetic diversity enhances the ability for plants and animals to respond to the changing world. Variation is not distributed randomly in space and time; it is influenced by historical, geographic and environmental factors. As such some populations will have greater genetic variation to be selected under different environmental conditions. Populations at the warm edge of species distributions will select for ‘warm’ genes that will become abundant and spread to other cooler populations. Geographic barrier (such as oceans, mountain ranges, and inhospitable habitat) may limit the spread of pre-adapted genes to Global Warming. This study will contrast the population genetic structure of Eucalypts with continuous and disjunct distributions. It will utilise existing plant collections and nuclear microsatellite markers optimised in molecular lab, along with high performance computing for statistical analyses. An enthusiastic student will be trained in DNA purification, PCR, genotyping of microsatillites, and population genetic analysis. The findings will be related to glasshouse experiments quantifying the ability of plants to respond to warming, and genes identified from RNA sequencing. This exciting project will result in a quality honours thesis and high-impact publication. Methods: DNA extraction of silica dried leaf material. PCR amplification of microsatellite markers. Genotyping and population genetic analyses. Ethics Application Requirements: No Key References: S.‐L. Tapper, M. Byrne, C. J. Yates, G. Keppel, S. D. Hopper, K. Van Niel, A. G. T. Schut, L. Mucina, G. W. Wardell‐ Johnson. Isolated with persistence or dynamically connected? Genetic patterns in a common granite outcrop endemic. Diversity and Distributions (Impact Factor: 6.12). 03/2014; DOI:10.1111/ddi.12185 Elen Oneal, David B. Lowry, Kevin M. Wright, Zhirui Zhu and John H. Willis. Divergent population structure and climate associations of a chromosomal inversion polymorphism across the Mimulus guttatus species complex. Accepted manuscript online: 2 MAY 2014 07:25AM EST | DOI: 10.1111/mec.12778 Rymer PD, Sandiford M, Harris SA, Billingham MR, Boshier DH (2013) Remnant Pachira quinata pasture trees have greater opportunities to self and suffer reduced reproduction due to inbreeding depression. Heredity. [JIF 4.110] Rymer PD, Dick CW, Vendramin GG, Buonamici A, Boshier D (2013) Recent phylogeographic structure in a widespread ‘weedy’ Neotropical tree species, Cordia alliodora (Boraginaceae). Journal of Biogeography. [Cited 2, JIF 4.863] Rymer PD, Manning JC, Goldblatt P, Powell MP, Savolainen V (2010). Evidence of recent and continuous speciation in a biodiversity hotspot: a population genetic approach in southern African gladioli (Gladiolus; Iridaceae). Molecular Ecology 19(21): 4765-4782. [Cited 10, JIF 6.275] M. Rossetto, D. Crayn, A. Ford, P. Ridgeway, P.D. Rymer (2007) The comparative study of range-wide genetic structure across related, co-distributed rainforest trees reveals contrasting evolutionary histories. Australian Journal of Botany, 55, 416-424. [Cited 11, JIF 1.204] P.D. Rymer, D.J. Ayre (2006) Does genetic diversity and gene flow vary with rarity in obligate seeding Persoonias (Proteaceae)? Conservation Genetics, 7, 919-930. [Cited 5, JIF 2.183] 170 Microbiology 171 Title of Project: Investigation into the role of protein kinase CK2 in metal ion uptake by fluorescent imaging (FOR Code/s): 0601 Biochemistry and Cell Biology; 0605 Microbiology Supervisor: Dr Ming J Wu Contact: [email protected] Co-supervisor: Dr Yossi Buskila Contact: [email protected] Location of Project: UWS, Campbelltown Project Background Protein kinase CK2 is the first kinase discovered and many questions still remains open. It is certain, based on the accumulated findings of the past decades, that the kinase plays multiple roles in regulating cellular functions, including cell proliferation, cell cycle, and apoptosis. The fact that it is constitutively active demonstrates its prominence and necessity to the cell’s survival. Despite the intensive research activities on CK2, there is a clear deficiency of data addressing its potential role in metal ion homeostasis. In this project, by the means of metal-specific fluorescent imaging, the role of CK2 in metal ion uptake will be investigated using Saccharomyces cerevisiae and mammalian cell lines. The key advantage of S. cerevisiae is the availability of CK2 subunit knockout mutants (cka1∆, cka2∆, ckb1∆ and ckb2∆). The conservation of genes and biological processes between the yeast and mammalian cell makes the findings relatable from one to another. Fluorescent imaging is to be carried out for quantification of metal ion uptake by using specific fluorophores for aluminium (Al3+), calcium (Ca2+), zinc (Zn2+) and chromium (Cr6+). Aim of Study: To uncover the role of CK2 in metal ion uptake Methods: The experimental approaches include: (1) preparation of the yeast (wild type and mutants) and mammalian cells; (2) quantification of metal ions influx by fluorescent imaging. Ethics Application Requirements: Not applicable Key References: To be provided on request 172 Title of Project: Survival of Cryptosporidium parvum in animal faeces (FOR Code/s): 0605 Microbiology; 060502 Infectious Agents Supervisor: Michelle Moffitt Contact: [email protected] Andrew Ball (Sydney Catchment Authority) Co-supervisor: Colin Stack Contact: [email protected] Location of Project: Campbelltown campus and Sydney Catchment Authority Project Background In Australia the critical contaminant in many source waters used for drinking-water supply is Cryptosporidium, which is the focus of considerable quantitative microbial risk assessment (QMRA) activity. Wild animals and livestock are the main source of Cryptosporidium oocysts in many drinking-water catchments and may pose a significant risk of waterborne disease. The prevalence and concentration of Cryptosporidium in animal dung and the amount of accumulated dung in the catchment are elements of risk assessment that have been studied but the survival times of infective oocysts in animal dung under ambient conditions is not well understood. This project will be conducted by the successful applicant of a $10 000 student scholarship funded by Water Research Australia. To apply for the scholarship, please visit the following website http://www.waterra.com.au/educationprogram/scholarship-initiatives/projects-commencing-2015-seeking-students/. The successful applicant will also have the opportunity to travel interstate to national Water Research Australia meetings and network with members in the water industry. This is a great opportunity for a student wishing to work in the water industry. Scholarship applications close October 31st. Aim of Study: This project will examine the decimal reduction times in infective oocysts in seeded animal dung under various controlled conditions of temperature and humidity and in the field to provide estimates of survival time that can be used in quantitative microbial risk assessment. Methods: obtain quantity of dung from cattle and sheep, seed with a known concentration of infectious C. parvum and homogenise storage of artificial scats seeded with oocysts under various conditions quantify oocysts and measure oocyst infectivity periodically using eukaryotic cell cultures calculate oocyst survival times (T90) under the various conditions Ethics Application Requirements: None Key References: King BJ, Monis PT. Critical processes affecting Cryptosporidium oocyst survival in the environment. Parasitology. 2007;134(Pt 3):309-23. 173 Title of Project: Survival of Cryptosporidium parvum in animal faeces (FOR Code/s): 0605 Microbiology; 060502 Infectious Agents Supervisor: Michelle Moffitt Contact: [email protected] Andrew Ball (Sydney Catchment Authority) Co-supervisor: Colin Stack Contact: [email protected] Location of Project: Campbelltown campus and Sydney Catchment Authority Project Background In Australia the critical contaminant in many source waters used for drinking-water supply is Cryptosporidium, which is the focus of considerable quantitative microbial risk assessment (QMRA) activity. Wild animals and livestock are the main source of Cryptosporidium oocysts in many drinking-water catchments and may pose a significant risk of waterborne disease. The prevalence and concentration of Cryptosporidium in animal dung and the amount of accumulated dung in the catchment are elements of risk assessment that have been studied but the survival times of infective oocysts in animal dung under ambient conditions is not well understood. This project will be conducted by the successful applicant of a $10 000 student scholarship funded by Water Research Australia. To apply for the scholarship, please visit the following website http://www.waterra.com.au/educationprogram/scholarship-initiatives/projects-commencing-2015-seeking-students/. The successful applicant will also have the opportunity to travel interstate to national Water Research Australia meetings and network with members in the water industry. This is a great opportunity for a student wishing to work in the water industry. Aim of Study: This project will examine the decimal reduction times in infective oocysts in seeded animal dung under various controlled conditions of temperature and humidity and in the field to provide estimates of survival time that can be used in quantitative microbial risk assessment. Methods: obtain quantity of dung from cattle and sheep, seed with a known concentration of infectious C. parvum and homogenise storage of artificial scats seeded with oocysts under various conditions quantify oocysts and measure oocyst infectivity periodically using eukaryotic cell cultures calculate oocyst survival times (T90) under the various conditions Ethics Application Requirements: None Key References: King BJ, Monis PT. Critical processes affecting Cryptosporidium oocyst survival in the environment. Parasitology. 2007;134(Pt 3):309-23. 174 Title of Project: Investigating the association between altered cholesterol and fat metabolism, and redox (antioxidant) balance and free radical accumulation/damage in cells. (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact:[email protected] Co-supervisor: Contact: Location of Project:Campbelltown campus Project Background Maintenance of an optimal redox environment in cells (i.e. reducing/oxidising) is critical for functioning of many cellular processes and for protecting cells against the damaging effects of reactive oxygen species (ROS). Cells are continually exposed to reactive oxygen species (ROS or free radicals) as part of normal metabolism. These ROS are toxic, affect redox balance, and have been implicated in many diseases including cancer, cardiovascular disease and arthritis. Key cellular systems (e.g. glutathione) maintain redox balance. Lipid metabolism and maintenance of an optimal redox environment are intimately linked through their requirement for NADPH as a cofactor. Substantial NADPH supplies are consumed in maintaining redox (antioxidant) systems as well as in the synthesis of lipids e.g. sterols (ergosterol/cholesterol) and fatty acids. Equally synthesis of sterols consumes appreciable levels of oxygen, and membrane sterol composition modulates oxygen diffusion. Sterols therefore may function in protecting of cells against oxygen or more specifically ROS (i.e. free radicals). Altered lipid metabolism, redox balance and/or ROS accumulation are associated with many diseases including, diabetes and neurodegenerative diseases including Alzheimer’s and Parkinson’s. Surprisingly an in depth understanding of how abnormal lipid metabolism affects redox/antioxidant defences, and detoxification of ROS has not been thoroughly investigated. Conversely how changes in redox/ROS affect lipid metabolism has not been studied in detail. Aim of Study: This project will study how the DNA synthesis and repair mechanisms of cells is impacted by changes in redox balance. The project also aims to study the converse, that is how changes in DNA homeostasis affect a cells ability to maintain redox balance and detoxification of reactive oxygen species. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) to study the extent to which lipid metabolic pathways, redox homeostasis and ROS production are inter-connected. These resources include novel redox sensing probes based on green fluorescent protein (roGFP) that can selectively measure dynamic changes in redox balance in real-time in live cells. Production of free radical species will also be measured. This project will use a range of instrumentation and techniques including flow cytometry, fluorescence microscopy and assays detecting DNA damage. The project will also exploit the vast resources of genome-wide deletion/overexpression strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, as well as gene libraries that allow researchers to selectively overexpress most genes in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to test almost any hypotheses. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 175 Title of Project: Investigating the link between DNA synthesis/repair, redox balance and production of free radicals (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact:[email protected] Co-supervisor: Contact: Location of Project:Campbelltown campus Project Background Maintenance of an optimal redox environment in cells (i.e. reducing/oxidising) is critical for functioning of many cellular processes and for protecting cells against the damaging effects of certain free radical species. Cells are equipped with key systems (e.g. glutathione) that maintain redox balance. Altered redox balance is associated with many diseases including, cancer, diabetes, neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases, and has been implicated as an important factor regulating cell growth and ageing. Cells of are continually exposed to reactive oxygen species (ROS or free radicals) as part of normal metabolism. These ROS are toxic, affect redox balance, and have been implicated in many diseases including cancer, cardiovascular disease, arthritis and those listed above. Altered lipid metabolism has also been associated with many of the above diseases. Maintenance and repair of DNA and maintenance of an optimal redox environment are closely linked through their requirement for NADPH as a cofactor. NADPH is used in the synthesis of DNA but is also used to keep redox/protective systems in balance. Combined treatments of cells with agents that affect redox systems in conjunction with DNA damaging agents has shown strong efficacy in treatment of some cancers. Surprisingly there an in depth understanding of how changes in DNA metabolism affect the ability of cells to maintain their redox environment and vice-versa is lacking. Aims: This project will study how the DNA synthesis and repair mechanisms of cells is impacted by changes in redox balance. The project also aims to study the converse, that is how changes in DNA homeostasis affect a cells ability to maintain redox balance and detoxification of reactive oxygen species. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) to study the extent to which lipid metabolic pathways, redox homeostasis and ROS production are inter-connected. These resources include novel redox sensing probes based on green fluorescent protein (roGFP) that can selectively measure dynamic changes in redox balance in real-time in live cells. Production of free radical species will also be measured. This project will use a range of instrumentation and techniques including flow cytometry, fluorescence microscopy and assays detecting DNA damage. The project will also exploit the vast resources of genome-wide deletion/overexpression strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, as well as gene libraries that allow researchers to selectively overexpress most genes in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to test almost any hypotheses. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 176 Title of Project: Shining a light on the molecular and cellular mechanisms underlying Trichoptyton rubrum infection. (FOR Code/s): 060505; 060502 Supervisor: Colin Stack Contact: E-mail: [email protected] Tel: 46203237 Co-supervisor: Oliver Morton Contact: E-mail: [email protected] Tel: 46203446 Location of Project: Campbelltown Campus Project Background: Trichophyton spp. are fungi that cause a spectrum of superficial infections in humans such as athlete’s foot and ringworm. These fungi rarely cause serious disease but can be difficult to treat leading to prolonged periods of discomfort. Amongst the treatment options available are the topical application of fungicides in creams, however these can have poor penetration into tissues such as nails. Novel treatments include the use of photodynamic therapy (PDT) where light is used to activate potent antimicrobials at the site of infection however very little is known about the effects of this procedure on human cells. Aim of Study: The aim of the study is to understand the mechanism through which the antimicrobial agent rose bengal inhibits fungal growth when used in combination with PDT and to identify how T. rubrum responds to suboptimal doses of PDT. The study will also aim to decipher the molecular and cellular interactions that take place between the fungus and host during the course of an infection. The effect of serine protease inhibitors on the progression of infection will also be studied. Methods: This study will involve the culture of epithelial and fungal cells, the use of light emitting diodes in PDT, protein isolation and purification, serine protease assays, 2-dimensional gel electrophoresis, and mass spectrometry. Ethics Application Requirements: No ethics applications required. Key References: Leng W., liu T., Li R., Wei C., Zhang W., and Jin Q. (2008) Proteomics profiling of dormant Trichophyton rubrum conidia. BMC Genomics, 9; 303 doi: 10.1186/1471-2164-9-303. Cronin L., Moffitt M., Mawad D., Morton OC, Lauto A., and Stack C. (2014) An in vitro study of the photodynamic effect of rose bengal on Trichophyton rubrum. J. Biophotonics 6; 410-417 doi: 10.1002/jbio.201200168. Liu T., Xu X., Leng W., Xuew Y., Dong J., and Jin Q. (2014) Analysis of gene expression changes in Trichophyton rubrum after skin interaction. J. Med. Microbiol., 5: 642-648. doi: 10.1099/jmm.0.059386-0. 177 Title of Project: The interaction between mitochondrial function and sphingolipid metabolism. Implications for programmed cell death and human diseases. (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact:[email protected] Co-supervisor: Contact: Location of Project:Campbelltown campus Project Background Sphingolipids play key roles in a broad range of cellular processes including: the formation of lipid micro domains “rafts” in membrane bilayers, that influence protein sorting and signal transduction; signaling molecules in cell differentiation, growth and cell cycle progress/arrest, cholesterol metabolism and stress signaling; and immune function, endocytosis and programmed cell death. Due to the role of sphingolipids in important cellular processes the impact of altered sphingolipid metabolism can have very serious consequences for cells. Altered sphingolipid metabolism has also been shown to play an important role in the pathobiology of diseases including: cancer, diabetes and metabolic syndrome; heart disease; Alzheimer’s disease; Niemann-Pick; and immune dysfunction. In some cancers altered sphingolipid homestasis appears to play a key role in disease progression. Crucially, despite the role of sphingolipids in a diverse range of serious human diseases, on a global or a “systems-wide” level very little is known of how the broad array of cellular functions influence sphingolipid homeostasis and/or vice-versa. Recently we have identified novel links between mitochondrial function and sphingolipid metabolism. This is a two bidirectional effect whereby altered mitochondrial function impacts on sphingolipid metabolism, and conversely, we have identified cases were altered sphingolipid metabolism disrupts mitochondrial respiration. Aims: To investigate how mitochondrial dysfunction (e.g. respiratory ) leads to abnormal sphingolipid homeostasis, and, vice-versa how defects in sphingolipid metabolism impact mitochondrial function, including respiratory capacity. This study also aims to identify on a genome-wide level how the various process conducted in cells affects sphingolipid metabolism. The findings will help us to better understand the factors that contribute to abnormal sphingolipid metabolism and inform our understanding of diseases (e.g. metabolic syndrome, cancer, neurodegenerative diseases) where altered sphingolipid metabolism has been implicated. Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast) as well as leading edge techniques and resources. The project will exploit the genome-wide deletion strain collections, drug treatments, a range of recombinant DNA and protein analysis techniques, biochemical assays, lipid analyses, as well as suite of powerful yeast strain libraries that allow us to selectively manipulate almost all genes (deletion or overexpression) in the yeast genome. The advantage of such resources is that allow almost unlimited capacity to manipulate the genetics and biology of cells to readily test most hypotheses. This project will utilise sophisticated analytical methodology including flow cytometry, mass spectrometry and fluorescent microscopy If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 178 Title of Project: Understanding why depleting the key antioxidant, glutathione, leads to catastrophic loss of mitochondrial DNA in cells. (FOR Code/s): 601, 604, 605 Supervisor: Dr Gabriel Perrone Contact: [email protected] Co-supervisor: Contact: Location of Project: Campbelltown campus Project Background Glutathione is an essential molecule that acts as a key redox buffer, antioxidant and protectant against toxins such as heavy metals and drugs. Decreased cellular levels of GSH in cells leads to a range of detrimental effects including increased accumulation of free radicals and cellular damage, defects in protein folding and severe disturbance of iron metabolism. Glutathione is non to decrease during the ageing process and GSH depletion has been linked with numerous disease process including Alzheimer’s disease, Parkinson’s disease, diabetes, and alcoholic liver disease. In the latter case depletion of mitochondrial glutathione has been implicated in the disease process. Glutathione depletion is also known to occur as part of the natural ageing process by also can be caused acutely through exposure to many toxins including heavy metals, poisons and medications (e.g. paracetamol). We have recently demonstrated that GSH depletion in yeast leads to a catastrophic and complete loss of the mitochondrial DNA from cells (mtDNA). Loss of mDNA was found to correlate with iron overload in mitochondria, a burst of reactive oxygen species (ROS) production. While we have some key pieces of the puzzle, it is still unclear what the precise mechanisms underlying mtDNA loss are. Since damage or loss of mtDNA poses serious implications for human health and disease the significance of understanding the mechanism(s) involved are anticipated to be far reaching. Aims: This project will aim to elucidate how the mechanisms through which glutathione depletion affects mtDNA integrity. The project will also aim to study mitochondrial glutathione homeostasis using high through put flow cytometry and novel in vivo redox probes based on roGFP (redox GFP). Methods: This project will exploit the extensive genetic and cell biology resources of the model eukaryotic organism, Saccharomyces cerevisiae (budding yeast), including genome-wide collections of strains that either have a gene deleted or conversely overexpressed. The project will involve the use of highly sophisticated flow cytometry methods to analyse mtDNA loss, mitochondrial energization, mitochondrial redox and ROS production. These resources used will include novel redox sensing probes based on green fluorescent protein (roGFP) that can selectively measure dynamic changes in redox balance in mitochondria in real-time. Production of free radical species will also be measured using fluorescent dyes. This project will use a range of instrumentation and techniques including flow cytometry, fluorescence microscopy and assays detecting mitochondrial DNA damage. The project will also exploit the vast resources of genome-wide deletion/overexpression strain collections, drug treatments, a range of recombinant DNA biochemical assays, as well as gene libraries that allow researchers to selectively overexpress most genes in the yeast genome. If you are interested in further details please arrange a time to meet with me to discuss the projects in person Ethics Application Requirements: None required Key References: A range of relevant references can be provided upon request 179 Title of Project: Molecular investigation into the effect of manganese and hydrogen peroxide on the phenotype of yeast hom6Δ mutant (FOR Code/s): 0601 Biochemistry and Cell Biology; 0605 Microbiology Supervisor: Dr Ming J Wu Contact: [email protected] Co-supervisor: Dr Cindy Kersaitis Contact: [email protected] Location of Project: UWS, Campbelltown Project Background HOM6 encoding homoserine dehydrogenase is a major gene in the aspartate pathway which leads to biosynthesis of threonine, methionine and cysteine. The phenotypes of the gene deletion mutant (hom6∆) in a variety of cultural conditions have previously provided meaningful insights into the biological roles of HOM6 and its upstream intermediate metabolites such as aspartate β-semialdehyde. This metabolic pathway is heavily targeted by the recent research for antifungal drug development because of its uniqueness for fungi and its absence in mammalian hosts. We have demonstrated previously that both manganese (Mn2+) and hydrogen peroxide (H2O2) can promote the growth of hom6Δ, with the latter exerting such effect only under anaerobic condition. This Honours project intends to delineate the underlying molecular mechanism for the effect of these two agents on hom6Δ mutant. Aim of Study: To delineate the underlying molecular mechanism for the positive effect of Mn2+ and H2O2 on the growth of hom6Δ mutant Methods: Three experimental approaches will be carried out in this project, namely, (1) manipulation of aspartic acid pathway by supplementation of specific metabolites; (2) manipulation of aspartic acid pathway by enzyme inhibitors; (2) molecular analysis of gene expression by quantitative polymerase chain reaction (qPCR). It is anticipated that the outcomes should provide a basis for the underlying molecular mechanism of the findings with Mn2+ and H2O2 on the growth of hom6Δ mutant Ethics Application Requirements: Not applicable Key References: To be provided on request 180 Title of Project: Natural products produced by bacteria and fungi (FOR Code/s): 0605 Microbiology Supervisor: Michelle Moffitt Contact: [email protected] Co-supervisor: Contact: Location of Project: Campbelltown campus Project Background Many bacteria produce small molecules during secondary metabolism that have specific biological activities. These molecules, referred to as natural products, are thought to have evolved to enhance the survival of the microorganism in it’s environment. Their biological activities are of interest to humans for their pharmaceutical benefits. They also tell us about the ecology of the microbial environment and how microorganisms interact with each other. We are also particularly interested in the way in which these chemicals are constructed by bacteria in Nature. Working together with the University of New South Wales, this project will analyse bacterial and fungal strains that have been isolated from Antarctic soils. It is hypothesised that these strains produce novel antimicrobial or antifungal agents which give the organisms a competitive advantage and help them survive in this harsh environment. Aim of Study: To analyse the activity of natural products from Antarctic soil bacteria and fungi. Methods: This project will require microbial culturing techniques as well as antibacterial and antifungal testing. You will also employ microbial genetics and PCR techniques. Ethics Application Requirements: None Key References: 181 Title of Project: Protein arginine methylation – a key player in cellular events (FOR Code/s): 0601 mainly (but others including 0605, 0607 and 1109 may also apply depending on project) Supervisor: Sabine C. Piller Contact: [email protected] or 46203354 Co-supervisor: TBA depending on project Contact: Location of Project: Campbelltown but some projects may involve work on other campuses including Hawkesbury, Parramatta or external as indicated below Project Background Protein arginine methylation is a post-translational modification like phosphorylation, acetylation and ubiquitination. Recent research and advances in technology have revived the initial research carried out on protein methylation in the early 1960ies (1), and protein arginine methylation has become one of the hot topics of research in a variety of fields including virology, cell biology and molecular mechanisms of disease as well as potential drug target development. Protein arginine methylation is a likely key modulator of cellular processes such as transcription, cell signalling, nuclear transport, ageing and cellular stress which has implications for a wide range of diseases including cancer, cardiovascular diseases, viral infections, lung disease and potentially neuronal diseases. Protein arginine methyltransferases (PRMTs) are a protein family that is highly conserved and can even be found in yeast (2). There are now 4 types of PRMTs known and arginine residues can be mono-methylated on the terminal nitrogen (by types, I, II and III) or on an internal nitrogen (by type IV). Arginine residues can further be modified by type I PRMTs resulting in asymmetric dimethylation of the terminal nitrogen, while type II PRMTs result in symmetric dimethylation of the terminal nitrogens. This field of research is fast moving and new findings about the mechanism and importance of protein arginine methylation are discovered and published every month. My lab has started to study protein arginine methylation initially in the HIV virus (3, 4) and work continues to clarify the role of protein arginine methylation of 2 HIV proteins. In addition, we have obtained preliminary data suggesting that arginine methylation may be important in the ageing process and may overlap with traditional Chinese herbal medicines used as anti-ageing compounds. Further, the work of one of my PhD students in 2011 has identified neuronal proteins that are methylated. We are in the process of studying the importance and role of protein arginine methylation in neurons and neuronal diseases as well as in other diseases including hepatitis, liver diseases, and cancer. Other areas of interest include studying the role of protein arginine methylation in cyanobacteria, bacteria and other microorganisms (collaborative projects with Dr Michelle Moffitt, Dr Oliver Morton, and Dr Colin Stack), in plants and mycorrhizal fungi (in collaboration with Dr Jonathan Plett at the HIE) and in ion channel forming proteins. Honours projects are available for each of the aims of the overall focus to elucidate the molecular mechanism of protein arginine methylation as listed below. Aim of Study: The major aim of the work conducted in my laboratory is to better understand protein arginine methylation and its importance in cellular pathways and disease in order to identify potential future drug targets to combat a variety of diseases. The specific aims and individual projects include: 1. Role of protein methylation in neurons and neuronal disease 2. Role of protein methylation in liver disease 3. Role of protein methylation in the regulation of cell cycle and cancer (in collaboration with Dr Qihan Dong) 4. Role of protein methylation in mycorrhizal fungi (in collaboration with Dr Jonathan Plett, HIE, Hawkesbury) 5. Role of protein methylation in microorganisms including cyanobacteria (co-supervised project with supervisor Dr Michelle Moffitt) 6. Role of protein methylation in ion channel forming proteins 7. Role of protein methylation in nuclear transport 8. Role of protein methylation in viral diseases including HIV, HCV, HBV 9. Role of protein methylation in ageing 10. Role of AdOx in protein and DNA methylation (in collaboration with Dr Patrice Castignolles, Parramatta) Methods: The major methods and techniques employed include, cell and tissue culture techniques (bacteria, yeast, eukaryotic cells), transformation, transfection, plasmid DNA preparations and purifications, PCR, site-directed mutagenesis, SDSPAGE, agarose gels, Western Blotting, immunoprecipitation, FACS studies, fluorescent confocal microscopy, and potentially some advanced microscopy techniques (FRET) ; 2D gels and mass spectrometry. Reagents and infrastructure as well as expertise with techniques is available in the Piller laboratory and from national and 182 international collaborators (including Prof Muench at SoM, Ass/Prof Roslyn London at UWA, Dr Michelle Moffitt, Dr Colin Stack, Dr Oliver Morton, Dr Patrice Castignolles, Dr Qihan Dong; SSH; Dr Jonathan Plett; HIE). Ethics Application Requirements: Most experiments are performed in cell lines and ethics approval for mouse work of primary cultured neurons is current and valid until end of 2015. Key References: 1) Paik et al. 2007 Trends in Biochemical Sciences 32(2):146-152; 2) Bedford and Clarke 2009 Molecular Cell 33: 1-13; 3) Willemsen et al. 2006 Retrovirology 3:92; 4) Mirto & Piller 2010 Future Medicine - HIV Therapy 4(1): 65. 183 Title of Project: Examining the cell surface components on fungi that are recognised by phagocytic cells. What makes a tasty fungus? (FOR Code/s): 0605 Supervisor: Oliver Morton Contact: 0246203446 [email protected] Co-supervisor: Gabriel Perrone Contact: 0246203286 [email protected] Location of Project: Campbelltown Campus Project Background: The cells of the innate immune system, neutrophils, macrophages and dendritic cells are important for defence against pathogenic fungi. Inhaled fungi are ingested through phagocytosis by macrophages and neutrophils in the alveoli. The fungi within the phagocytic vacuoles are usually killed but can overwhelm the immune cell if they are present in sufficient numbers. Many pathogens are able to evade phagocytosis by covering or shedding surface receptors that are recognised by the immune system, this study will examine which cell surface molecules make fungi attractive to immune cells. Aim of Study: The aim of this study is to determine which molecules influence the ability of immune cells and mycophagous protozoa to ingest fungi. To do this we will screen the Saccharomyces cerevisiae deletion mutant library to identify mutants which cause increases or decreases in the rate of phagocytosis. We will determine if human immune cells (THP1 monocytes) and phagocytic protozoa (Trichomonas vaginalis) recognise the same components of the fungal cell. Methods: The students will gain experience in a number of techniques including sterile culture of protozoa and tissue culture of human cell lines. The analysis of the cellular interactions will be conducted using several methods including flow cytometry to measure uptake of fungi by phagocytic cells and confocal microscopy. The student will utilise high throughput methods to screen S. cerevisiae mutants. This project will utilise the EM facility in Parramatta to generate high quality images of the fine details of interactions between the phagocytic cells and the fungi. Ethics Application Requirements: None required Key References: Pereira-Neves A, Benchimol M. (2007) Phagocytosis by Trichomonas vaginalis: new insights. Biol Cell. 99(2):87101.PMID:17029588 Chamilos G, Lionakis MS, Lewis RE, Kontoyiannis DP. (2007) Role of mini-host models in the study of medically important fungi. Lancet Infect Dis; 7(1):42-55. PMID:17182343 Morton CO, Varga JJ, Hornbach A, Mezger M, Sennefelder H, Kneitz S, Kurzai O, Einsele H, Nierman W, Rogers TR & Loeffler J (2011). The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro. PLoS One 6(1): e16016. 184 Title of Project: Examining the effects of antifungal drugs on the interaction between phagocytic cells and pathogenic fungi. (FOR Code/s): 0605 Supervisor: Oliver Morton Contact: 0246203446 [email protected] Co-supervisor: Colin Stack Contact: 0246203237 [email protected] Location of Project: Campbelltown Campus Project Background: The cells of the innate immune system, neutrophils, macrophages and dendritic cells are important for defence against pathogenic fungi. Inhaled fungi are ingested through phagocytosis by macrophages and neutrophils in the alveoli. The timing of antifungal treatment is critical in achieving clearance of infection but the effects that these drugs have on interactions between fungi and immune cells is unclear. Aim of Study: The aim of this study is to determine if antifungal drugs affect the functioning of immune cells during interactions with pathogenic fungi. Methods: The methods used will be RT-qPCR to measure the expression of immune genes by the immune cells and to measure expression of fungal virulence genes. Flow cytometry will be used to quantify defects in the ability of cells to ingest and kills pathogens. Various forms of microscopy including confocal microscopy and electron microscopy will be used to monitor the experiments. Ethics Application Requirements: None required Key References: Morton CO, Varga JJ, Hornbach A, Mezger M, Sennefelder H, Kneitz S, Kurzai O, Einsele H, Nierman W, Rogers TR & Loeffler J (2011). The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro. PLoS One 6(1): e16016. Morton CO, Bouzani M, Loeffler J & Rogers TR (2012). Direct interaction studies between Aspergillus fumigatus and human immune cells; what have we learned about pathogenicity and host immunity? Frontiers in microbiology, 3, 413.(PMID: 23264771). Serhan G, Perrone GG, Stack CM, Morton CO (2014). The polyene antifungals, amphotericin B and nystatin, cause cell death in Saccharomyces cerevisiae by a distinct mechanism to amphibian-derived antimicrobial peptides. Annals of Clinical Microbiology and Antimicrobials, 13:18. PMID: 24884795 185 Physiology 186 Field of Research: Molecular Physiology / Neuroscience (FOR Code/s): 1109, 0606, 1101, 0601 Title of Project: Defining Molecular Mechanisms Underlying Multiple Sclerosis Supervisor: Prof. Jens Coorssen Email: [email protected] Co-supervisor: Dr. Simon Myers Email: [email protected] Campus project is offered and conducted: Campbelltown Telephone: 46203802 Telephone: 46203383 Background (max 500 words) Multiple Sclerosis (MS) is a CNS disorder of as yet undefined aetiology. It has long been assumed to be an autoimmune disorder, and there is no doubt that such a component is an active part of the disease process and its progression. Nonetheless, it has also become apparent that this aspect alone does not necessarily explain the initiation/development of MS; a newer hypothesis holds that MS may first and foremost be a degenerative disorder, specifically an oligodendrocytosis. We are currently engaged in a research project to better distinguish between these aspects of MS using different mouse models as well as blood/white cell samples from human patients. The outcomes will be important in terms of enabling earlier and/or better identification of (i) MS patients; (ii) prognostic indicators; and (iii) new therapeutic targets. Aim of Study: Hypothesis – MS is fundamentally a degenerative disease. Aims - Use detailed proteomic or lipidomic analyses to better understand molecular changes occurring in mouse models of MS - Identify specific CNS changes; - Identify specific changes in white cells Specific details for an Honours project can be discussed and refined with a suitable candidate. Methods: We have well established protocols for tissue processing, protein and lipid extraction, and all aspects of (i) proteomic analyses using a refined, quantitative 2D gel approach; and (ii) lipidomic analyses using a refined, quantitative high performance thin layer chromatography approach. Ethics Application Requirements: Both human (hospital) and animal ethics approval are in place. 187 Field of Research: Molecular Physiology / Neuroscience (FOR Code/s): 1109, 0601, 0606 Title of Project: Examining Molecular Mechanisms Underlying Ca2+ Triggered Neurotransmitter Release Supervisor: Prof. Jens Coorssen Email: [email protected] Telephone: 46203802 Co-supervisor: Dr. Chandra Malladi Email: [email protected] Telephone: 46203813 Campus project is offered and conducted: Campbelltown Background (max 500 words) Ca2+ triggered release of neurotransmitters (i.e. regulated synaptic vesicle exocytosis) is the process underlying basic central nervous system functions such as learning and memory. This process is known to be disturbed in debilitating disease including depression, epilepsy, and schizophrenia. Understanding the essential molecular mechanisms of exocytosis is thus a rational approach to addressing such disorders. Aim of Study: Although the basic pathway leading to neurotransmitter release has been established, the current challenge is to identify components that mediate each stage [1, 2]. Using a bias-free small-molecule based approach coupled with molecular/functional analysis, our laboratory has previously identified several proteins and lipids as either critical or modulatory components [3-6]. We now aim to test the roles of these candidates utilising an in vitro neurotransmitter release assay. To this end, this project aims to: 1) Establish an in vitro synaptic vesicle exocytosis assay to monitor several stages of neurotransmitter release; and 2) utilise the developed assay to understand the specific roles of critical proteins and lipids. Methods: Synaptosomes (functional nerve terminals) and synaptic vesicles will be isolated from rat brain using established protocols, and electron microscopy will be used to verify the purity of these preparations. A time-resolved Förster resonance energy transfer (FRET) based fluorescence assay to monitor exocytosis is under development. Well established molecular assays are available in the lab to monitor global changes in protein and lipid composition, as required [7, 8]. Preliminary results have established this as a feasible approach. Ethics Application Requirements: Approval from the UWS Animal Ethics Committee is in place. Key References: 1. Becherer, U. and J. Rettig, Vesicle pools, docking, priming, and release. Cell Tissue Res, 2006. 326(2): p. 393407. 2. Rogasevskaia, T.P. and J.R. Coorssen, A new approach to the molecular analysis of docking, priming, and regulated membrane fusion. J Chem Biol, 2011. 4(3): p. 117-136. 3. Furber, K.L., D.M. Brandman, and J.R. Coorssen, Enhancement of the Ca(2+)-triggering steps of native membrane fusion via thiol-reactivity. J Chem Biol, 2009. 2(1): p. 27-37. 4. Furber, K.L., K.T. Dean, and J.R. Coorssen, Dissecting the mechanism of Ca2+-triggered membrane fusion: probing protein function using thiol reactivity. Clin Exp Pharmacol Physiol, 2010. 37(2): p. 208-217. 5. Churchward, M.A. and J.R. Coorssen, Cholesterol, regulated exocytosis and the physiological fusion machine. Biochem J, 2009. 423(1): p. 1-14. 6. Churchward, M.A., et al., Specific lipids supply critical negative spontaneous curvature--an essential component of native Ca2+-triggered membrane fusion. Biophys J, 2008. 94(10): p. 3976-3986. 7. Wright, E.P., et al., Top‐down proteomics: Enhancing 2D gel‐electrophoresis from tissue processing to high sensitivity protein detection. Proteomics, 2014. 8. Churchward, M.A., et al., Copper (II) sulfate charring for high sensitivity on-plate fluorescent detection of lipids and sterols: quantitative analyses of the composition of functional secretory vesicles. J Chem Biol, 2008. 1(1-4): p. 79-87. 188 Field of Research: 060603 Neurobiology Title of Project: Examination of the axon initial segment in retinal ganglion cells of the retinally degenerate (rd/rd) mouse. Supervisor: Dr. Morven Cameron Email: [email protected] Telephone: 02 4620 3853 Co-supervisor: Prof. John Morley Email: j. [email protected] Telephone: 02 4620 3748 Campus project is offered and conducted: Campbelltown Background (max 500 words) This project focuses on comparing structural differences in the axon initial segment (AIS) of retinal ganglion cells (RGCs) between the retinae of wild-type and blind mice (rd/rd). The retinally degenerate rd/rd mouse lacks both rods and cones, but retains interneurons and RGCs. After degeneration, light input to these post-synaptic neurons is lost, likely causing widespread changes in these neurons. The AIS is a proximal region of the axon that consists of a specialised complex of proteins required for action potential generation. Studies in other areas of the nervous system indicate that the structure of the AIS can be substantially altered when neuronal input is increased or decreased. This project aims to assess potential changes to the AIS of RGCs in the rd/rd retina following photoreceptor degeneration. Aim of Study: The Australian Bionic Eye project aims to activate RGCs with electrical stimulation in patients suffering from retinal degenerations. The AIS is the area on the RGC where electrical activation is most efficacious due to its high concentration of voltage-gated sodium channels. By characterising changes to the AIS after retinal degeneration, we aim to better target RGCs with electrical stimulation. Methods: This project will involve the following wet-lab techniques: cryogenic tissue slicing, immunohistochemistry and confocal laser microscopy. Ethics Application Requirements: This work is covered under ethics protocol A10396. Key References: Kaphzan, H., Buffington, S. A., Jung, J. I., Rasband, M. N., & Klann, E. (2011). Alterations in intrinsic membrane properties and the axon initial segment in a mouse model of Angelman syndrome. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 31(48), 17637–48. doi:10.1523/JNEUROSCI.4162-11.2011 Jensen, R. J., & Rizzo, J. F. (2008). Activation of retinal ganglion cells in wild-type and rd1 mice through electrical stimulation of the retinal neural network. Vision Research, 48(14), 1562–8. doi:10.1016/j.visres.2008.04.016 189 Plant Biology 190 Title of Project: Protein arginine methylation – a key player in cellular events (FOR Code/s): 0601 mainly (but others including 0605, 0607 and 1109 may also apply depending on project) Supervisor: Sabine C. Piller Contact: [email protected] or 46203354 Co-supervisor: TBA depending on project Contact: Location of Project: Campbelltown but some projects may involve work on other campuses including Hawkesbury, Parramatta or external as indicated below Project Background Protein arginine methylation is a post-translational modification like phosphorylation, acetylation and ubiquitination. Recent research and advances in technology have revived the initial research carried out on protein methylation in the early 1960ies (1), and protein arginine methylation has become one of the hot topics of research in a variety of fields including virology, cell biology and molecular mechanisms of disease as well as potential drug target development. Protein arginine methylation is a likely key modulator of cellular processes such as transcription, cell signalling, nuclear transport, ageing and cellular stress which has implications for a wide range of diseases including cancer, cardiovascular diseases, viral infections, lung disease and potentially neuronal diseases. Protein arginine methyltransferases (PRMTs) are a protein family that is highly conserved and can even be found in yeast (2). There are now 4 types of PRMTs known and arginine residues can be mono-methylated on the terminal nitrogen (by types, I, II and III) or on an internal nitrogen (by type IV). Arginine residues can further be modified by type I PRMTs resulting in asymmetric dimethylation of the terminal nitrogen, while type II PRMTs result in symmetric dimethylation of the terminal nitrogens. This field of research is fast moving and new findings about the mechanism and importance of protein arginine methylation are discovered and published every month. My lab has started to study protein arginine methylation initially in the HIV virus (3, 4) and work continues to clarify the role of protein arginine methylation of 2 HIV proteins. In addition, we have obtained preliminary data suggesting that arginine methylation may be important in the ageing process and may overlap with traditional Chinese herbal medicines used as anti-ageing compounds. Further, the work of one of my PhD students in 2011 has identified neuronal proteins that are methylated. We are in the process of studying the importance and role of protein arginine methylation in neurons and neuronal diseases as well as in other diseases including hepatitis, liver diseases, and cancer. Other areas of interest include studying the role of protein arginine methylation in cyanobacteria, bacteria and other microorganisms (collaborative projects with Dr Michelle Moffitt, Dr Oliver Morton, and Dr Colin Stack), in plants and mycorrhizal fungi (in collaboration with Dr Jonathan Plett at the HIE) and in ion channel forming proteins. Honours projects are available for each of the aims of the overall focus to elucidate the molecular mechanism of protein arginine methylation as listed below. Aim of Study: The major aim of the work conducted in my laboratory is to better understand protein arginine methylation and its importance in cellular pathways and disease in order to identify potential future drug targets to combat a variety of diseases. The specific aims and individual projects include: 1. Role of protein methylation in neurons and neuronal disease 2. Role of protein methylation in liver disease 3. Role of protein methylation in the regulation of cell cycle and cancer (in collaboration with Dr Qihan Dong) 4. Role of protein methylation in mycorrhizal fungi (in collaboration with Dr Jonathan Plett, HIE, Hawkesbury) 5. Role of protein methylation in microorganisms including cyanobacteria (co-supervised project with supervisor Dr Michelle Moffitt) 6. Role of protein methylation in ion channel forming proteins 7. Role of protein methylation in nuclear transport 8. Role of protein methylation in viral diseases including HIV, HCV, HBV 9. Role of protein methylation in ageing 10. Role of AdOx in protein and DNA methylation (in collaboration with Dr Patrice Castignolles, Parramatta) Methods: The major methods and techniques employed include, cell and tissue culture techniques (bacteria, yeast, eukaryotic cells), transformation, transfection, plasmid DNA preparations and purifications, PCR, site-directed mutagenesis, SDSPAGE, agarose gels, Western Blotting, immunoprecipitation, FACS studies, fluorescent confocal microscopy, and potentially some advanced microscopy techniques (FRET) ; 2D gels and mass spectrometry. Reagents and infrastructure as well as expertise with techniques is available in the Piller laboratory and from national and 191 international collaborators (including Prof Muench at SoM, Ass/Prof Roslyn London at UWA, Dr Michelle Moffitt, Dr Colin Stack, Dr Oliver Morton, Dr Patrice Castignolles, Dr Qihan Dong; SSH; Dr Jonathan Plett; HIE). Ethics Application Requirements: Most experiments are performed in cell lines and ethics approval for mouse work of primary cultured neurons is current and valid until end of 2015. Key References: 1) Paik et al. 2007 Trends in Biochemical Sciences 32(2):146-152; 2) Bedford and Clarke 2009 Molecular Cell 33: 1-13; 3) Willemsen et al. 2006 Retrovirology 3:92; 4) Mirto & Piller 2010 Future Medicine - HIV Therapy 4(1): 65. 192 Zoology 193 Field of Research: Ecology/Molecular Biology/Immunology Title of Project: Wombat mange Supervisor: Dr Julie Old Email:[email protected] Co-supervisor: Dr Lauren Young Email:[email protected] Campus project is offered and conducted: HWK Telephone: x1283 Telephone: NA Background (max 500 words) Wombats suffer from sarcoptic mange, a debilitating disease that eventually leads to their death. This project will incorporate field (habitat surveys and spotlighting) and laboratory skills (molecular biology) to investigate the role of mange in wombat populations. Several more specific projects are available in this area. Aim of Study: Investigate mange in wombats using laboratory and/or field skills. Methods: The projects involves field and/or molecular biology skills. Ethics Application Requirements: Ethics, biosafety and NSW NPWS licences have been granted. Risk assessments will be required. Key References: 194 Field of Research: Biochemistry/Microbiology/Immunology Title of Project: Lipid profiles in marsupial pouches over the different reproductive stages Supervisor: Dr Julie Old Email:[email protected] Telephone: x1283 Co-supervisor: Dr Jo-Anne Chuck Email:[email protected] Telephone: x9906 Campus project is offered and conducted: HWK/PTA Background (max 500 words) Marsupials are born without functional immune tissues and are therefore unable to mount specific immune responses. Despite this, marsupial neonates survive in the microbial-rich pouch. Recently, peptides have been identified in marsupial pouches at the time of oestrus with antimicrobial properties. Lipids secreted by the pouch skin of marsupials may also have antimicrobial properties, and play a role in innate immunity of young marsupials. The project can be adapted to allow to suit a chemistry, microbiology, biochemistry, or immunology student. Aim of Study: The project will identify lipids in the pouches of tammar wallabies (Macropus eugenii) during the different reproductive stages to determine if they may play a role in immunological protection of the neonatal marsupial. Methods: It is a laboratory-based biochemistry/immunology project, however some animal handling experience can be incorporated. Ethics Application Requirements: Risk assessments will be required. All other requirements are in place. Key References: Old J, Deane E (2000) Development of the immune system and immunological protection in marsupial pouch young. Dev Comp Immunol. 24, 445-454. ISSN 0145-305X 195 Field of Research: Molecular Biology/Immunology/Developmental Biology Title of Project: Marsupial immunology Supervisor: Dr Julie Old Email:[email protected] Co-supervisor: Dr Lauren Young Email:[email protected] Campus project is offered and conducted: HWK Telephone: x1283 Telephone:NA Background (max 500 words) Various projects are available in the area of marsupial immunology. Very little is known about Dasyurid marsupials (carnivorous marsupials), including their immunology, with many species in the Family listed as endangered or threatened. One of the key immunological questions in marsupials involves understanding how newborn marsupials survive the microbial onslaught in the pouch when they lack mature immune tissues and are therefore unable to mount their own immune response to pathogens. Aim of Study: The project aims to isolate the cDNA sequences for key immunological molecules using molecular techniques in the phascogale (Phascogale calura) and/or other Dasyurid species with the aim of increasing the understanding of the development and in the longer term function of their immune system. Once isolated the expression levels of these molecules will be determined using qPCR. Methods: The project involves molecular laboratory work as well as a small animal handling component with the animals housed on campus. Ethics Application Requirements: Ethics, biosafety and NSW NPWS licences have been granted. Risk assessments will be required. Key References: Old J, Deane E (2000) Development of the immune system and immunological protection in marsupial pouch young. Dev Comp Immunol. 24, 445-454. ISSN 0145-305X Belov K, Miller RD, Old JM, Young LJ (2013). Marsupial Immunology Bounding Ahead. Australian Journal of Zoology. 61, 24-40. ISSN 0004-959X 196 Title of Project: Turtle Conservation Team: Optimising Management to Address Turtle Declines (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Turtles are evolutionary survivors. Their hard protective shell and longevity has allowed them to survive 220 million years of natural selective pressures. But the combination of rapid, human-induced, changes (invasive species, harvesting and river regulation) has led to nearly half of all turtle fauna either endangered or extinct in the wild and without strategic intervention, much of the turtle lineage will be extinct by the end of the 21st century. Besides their conservation value as an iconic native vertebrate, the rapid decline of freshwater turtles may have far greater implications for the entire ecosystem, because their biomass is a similar magnitude to fis, and their role in the food chain is likely to be complex and diverse, yet completely unknown. Given their longevity, however, anthropogenic changes to the River ecosystem through the introduction of invasive species and changes in water management may only now be manifesting into population declines and local extinctions. This project will team with management agencies throughout the Murray River to identify and address threats to freshwater turtles, which are endangered in many states of Australia. The project will determine predation rates on turtle nests and nesting females, trial new fox management options, and assess turtle nesting preferences. TurtleSAT (TurtleSAT.org.au) will be used in this project, which will allow GIS spatial analysis to develop broad-scale predictive maps of turtle and fox ‘hotspots’ throughout the Murray River. You will be part of a large team of researchers, including post-docs and PhD students. You will have the opportunity to work closely with researchers from the University of Sydney, University of NSW and University of Canberra, as well as management agencies from three states. Animal Ethics approval is required. 197 Title of Project: Turtle Conservation Team: Impact of Dams on Turtle Movement and Recruitment (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Turtles are evolutionary survivors. Their hard protective shell and longevity has allowed them to survive 220 million years of natural selective pressures. But the combination of rapid, human-induced, changes (invasive species, harvesting and river regulation) has led to nearly half of all turtle fauna either endangered or extinct in the wild and without strategic intervention, much of the turtle lineage will be extinct by the end of the 21st century. Besides their conservation value as an iconic native vertebrate, the rapid decline of freshwater turtles may have far greater implications for the entire ecosystem, because their biomass is a similar magnitude to fis, and their role in the food chain is likely to be complex and diverse, yet completely unknown. Given their longevity, however, anthropogenic changes to the River ecosystem through the introduction of invasive species and changes in water management may only now be manifesting into population declines and local extinctions. Many river and wetland systems are fragmented by dams and altered ecologically through flow regulation, increasing the likelihood of population isolation for many aquatic species. Hence knowledge about the distribution and connectivity of species across important ecosystems, like the Murray-Darling Basin, both at the population and genetic levels, is essential if we are to manage them properly. Distinct metapopulations may exist between dams, as well as, in billabongs that are disconnected from the river except during major floods. If dispersal regularly occurs from certain key sites within these metapopulations, gene frequencies may be homogenised and local adaptation to fox predation may be reduced. Radiotracking (Telemetry) and molecular nuclear markers will be used to provide estimates of gene flow between populations to assess impact altering flow and connectivity. You will be part of a large team of researchers, including post-docs and PhD students. You will have the opportunity to work closely with researchers from the University of Sydney, University of NSW and University of Canberra, as well as management agencies from three states. Animal approval is required. 198 Title of Project: Turtle Conservation Team: Turtle Nest Adaptations (FOR Code/s): Ecology and Evolution (Group in 0602, 0603 and 0608) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Over the last 3 years, our group have discovered some amazing adaptations that embryos, hatchlings and even mothers use to improve survival of eggs in the nest. This project will focus on turtle emergence from the nest and what drives some turtles to over-winter in the nest for up to 9-12 months, surviving only on yolk provided in the egg. You will use military technology to find turtle nests and hatchlings underground. Laboratory experiments will run parrallel with field tests. Animal approval is required. 199 Title of Project: Power of Citizen Science: Using WomSAT to Manage Wombat Road Mortalities (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Australia Wide Project Background WomSAT is a new community mapping tool to that employs citizen science to determine the location of wombats throughout Australia. Many of these sightings are of road mortalities. This project will employ WomSAT and advanced GIS mapping techniques to determine hotspots of mortality. Important habitat data at these hotspots will be collected to determine if consistent patterns exist, which will allow harm mitigation strategies to be implemented. The project will also explore the social aspects of citizen science and promote WomSAT among management groups. Human Ethics approval may be required. 200 Title of Project: Impact of Domestic Cats on Native Wildlife in Urban Fringes (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Blue Mountains Project Background This project will evaluate the impact of cats on native wildlife in the Blue Mountains. The project will specifically target domestic cats and their owners to determine perception versus reality of domestic cat impacts. We will employ new control devices that spray liquids on cats as they investigate lures. The liquid can deliver a toxin, but in this project will spray domestic cats with coloured dyes- the colour will depend how far into the bush the cat has wandered. Owners will be encouraged to report the colour on the cat and their location through a website/app. The project will work very closely with environmental officers from Blue Mountains City Council. Animal and Human Ethics approval is required. 201 Title of Project: Turtle Conservation Team: Ecological Function of Turtles (FOR Code/s): Ecology and Conservation Biology (Group in 0602, 0608 and 0502) Supervisor: Dr Ricky Spencer Contact: [email protected] Co-supervisor: Contact: Location of Project: Hawkesbury and the Murray River Project Background Turtles are evolutionary survivors. Their hard protective shell and longevity has allowed them to survive 220 million years of natural selective pressures. But the combination of rapid, human-induced, changes (invasive species, harvesting and river regulation) has led to nearly half of all turtle fauna either endangered or extinct in the wild and without strategic intervention, much of the turtle lineage will be extinct by the end of the 21st century. Besides their conservation value as an iconic native vertebrate, the rapid decline of freshwater turtles may have far greater implications for the entire ecosystem, because their biomass is a similar magnitude to fis, and their role in the food chain is likely to be complex and diverse, yet completely unknown. Given their longevity, however, anthropogenic changes to the River ecosystem through the introduction of invasive species and changes in water management may only now be manifesting into population declines and local extinctions. The project will develop complex food webs in a range of habitats throughout eastern Australia. We will also manipulate turtle composition and abundance in experimental wetlands on the Hawkesbury campus and evaluate changes in food web dynamics and the relative importance of turtles on ecosystem function. The project will implement a large-scale experimental flood into Hawkesbury wetlands to evaluate the importance of regular inundations for food web dynamics and particular species of turtle. You will be part of a large team of researchers, including post-docs and PhD students. You will have the opportunity to work closely with researchers from the University of Sydney, University of NSW and University of Canberra, as well as management agencies from three states. Animal Ethics approval is required. 202 Agricultural & Veterinary Sciences Including: Crop & Pasture Production 203 Crop & Pasture Production 204 Title of Project: Effect of temperature on branching in rice starch (FOR Code/s): Agriculture - Crop & Pasture Improvement (Selection and Breeding) (070305) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Analytical Chemistry - Separation Science (030108) Supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Rachelle Ward Email: [email protected] Co-supervisor: Dr Laura Pallas Email: [email protected] Location of Project: Parramatta Project Background The amount of amylose and the nature of its branching are influenced by night temperatures [1]. This degree of branching has been shown to directly impact the cooking quality and texture of the rice grain. The Waxy gene has been linked to changes in amylose although this does not explain all observed changes in amylose. One hypothesis to explain the amylose structure is the changed activity of starch branching enzymes, however these environmental influences, in combination with genetic differences in the waxy and starch branching enzyme genes have not been studied in the Australian rice germplasm. This investigation will analyse 12 parental lines of rice (Oryza sativa) from the rice breeding program at the Yanco Agricultural Institute. These lines comprise three variations of interest in the waxy gene, high amylose and low amylose contents (identifiable by 3 SNPs within the Waxy gene) along with two possible combinations of Starch Branching Enzymes. The 12 plants will be grown in replicates of 12 in a glasshouse until flowering where half will be moved to a higher temperature glasshouse and the other half to a control/normal temperature. Upon harvesting the amylose from the grain will be measured, then extracted by use of hot water and the starch structure will be analysed by capillary electrophoresis and NMR. Aim of Study: To measure degrees of branching using NMR spectroscopy [2], as well as amylopectin-to-amylose ratio and amylose chain lengths using capillary electrophoresis to identify the effect of night time temperatures on the activity starch branching enzyme. Methods: Capillary electrophoresis, NMR spectroscopy. Ethics Application Requirements: Not applicable Key References: [1] PA Counce, RJ Bryant, CJ Bergman, RC Bautista, YJ Wang, TJ Siebenmorgen, KAK Molenhauer, JFC Meullenet, Rice milling quality, grain dimensions, and starch branching as affected by high night temperatures. AACC International, 2005, 82(6), 645-648 [2] M Gaborieau, H DeBruyn, S Mange, P Castignolles, A Brockmeyer, RG Gilbert, Synthesis and characterization of synthetic polymer colloids colloidally stabilized by cationized starch oligomers. Journal of Polymer Science Part A Polymer Chemistry, 2009, 47, 1836-1852 205 Engineering Including: Food Sciences Materials Engineering 206 Food Sciences 207 Title of Project: New methods to characterise breakfast cereals (FOR Code/s): Analytical Chemistry – Separation Science (030108) Food Sciences - Food Chemistry and Molecular Gastronomy (excl. Wine) (090801) Physical chemistry – Structure Chemistry and Spectroscopy (030606) Supervisor: Dr Patrice Castignolles Email: [email protected] Telephone: 9970 Co-supervisor: Dr Marion Gaborieau Email: [email protected] Telephone: 9905 Co-supervisor: Dr Ashok Shrestha Email: [email protected] Telephone: 1296 Location of Project: Parramatta Project Background Breakfast cereals are nutrient-dense processed foods and are expected to have several health benefits. They are expected to have a low glycemic index (low GI, which means that they are digested slowly [1]). Most of them are also externally fortified with folic acid (Pteroylglutamic acid) to prevent the incidence of neural tube defects [2]. Their analysis is complicated by the fact that they are only partially soluble in water [3]. Traditional methods of folic acid analysis such as HPLC, or microbiological assay are tedious and time consuming. Our preliminary results showed that capillary electrophoresis is a fast method to detect folic acid. It is also an excellent tool of the separation and detection of sugars [4,5]. Aim of Study: The aim of the project is to develop new methods for a faster, more accurate, and robust characterisation of cereal-based foods, based on free-solution capillary electrophoresis. Folates and sugars will be quantified. These methods could be compared to the established, but tedious and expensive, HPLC methods. The full samples will also be characterised with solid-state NMR spectroscopy and ATR IR spectroscopy, thus avoiding dissolution artefacts. Methods: Capillary electrophoresis, NMR spectroscopy, ATR IR spectroscopy, high-performance liquid chromatography (HPLC). Ethics Application Requirements: Not applicable Key References: [1] AC Dona, G Pages, RG Gilbert, M Gaborieau, PW Kuchel, Kinetics of in vitro digestion of starches monitored by time-resolved 1H nuclear magnetic resonance. Biomacromolecules, 2009, 10, 638-644 [2] J Arcot, A Shrestha, Folate: methods of analysis. Trends in Food Science & Technology, 2005, 16, 253–266 [3] S Schmitz, AC Dona, P Castignolles, RG Gilbert, M Gaborieau, Assessment of the extent of starch dissolution in dimethylsulfoxide by 1H NMR spectroscopy. Macromolecular Bioscience 2009, 9, 506-514 [4] JD Oliver, M Gaborieau, EF Hilder, P Castignolles, Simple and robust determination of monosaccharides in plant fibers in complex mixtures by capillary electrophoresis and high performance liquid chromatography. Journal of Chromatography A, 2013, 1291, 179-186 [5] JD Oliver, AA Rosser, CM Fellows, Y Guillaneuf, JL Clement, M Gaborieau, P Castignolles, Understanding and improving direct UV detection of monosaccharides and disaccharides in free solution capillary electrophoresis. Analytica Chimica Acta 2014, 809, 183 208 Materials Engineering 209 Title of Project: Effect of Conductive Carbon on the Structure and Electrochemical Performance of LiMnPO4 Cathode Material (FOR Code/s): 0303 and 0912 Supervisor: Dr Adriyan Milev Email: [email protected] Telephone: x9945 Co-supervisor: A/Prof Kamali Kannangara Email: [email protected] Telephone: x9952 Co-supervisor: Dr Laurel George Email: [email protected] Telephone: x9976 Location of the Project: Parramatta North Project Background After a number of cathode materials were found unsuitable for use in large lithium-ion electric vehicle batteries, lithium transition-metal phosphate (LiMPO4, M= Fe, Mn, Co) is now regarded as the best candidate [1, 2]. The advantages for LiMPO4 when compared to the existing electrodes such as LiCoO2, LiMnO2 include: improved safety through higher resistance to thermal runaway, longer cycle-life, low cost of raw materials, low toxicity, and high thermal stability at fully charged state. So far, only one member of this class, LiFePO4, has been employed in advanced batteries. The research is now focused on the more challenging LiMPO4 (M = Mn, and Co) structures, which have higher theoretical energy density (~700 Wh/kg and ~800Wh/kg, respectively) compared to LiFePO 4 (~580 Wh/kg). The LiMnPO4is currently the most promising cathode material for Li-batteries considering its low cost, environmental safety, high theoretical capacity and operating voltage (4.1 V)achievable within the stability window of well-known carbonate ester-based electrolytes. However, few reported studies have demonstrated less than 50% of the theoretical specific capacity even at low rates [3, 4]. This, along with lower electronic conductivity, (~10−10 Scm−1) means it is difficult to obtain satisfying electrochemical activity. Due to its poor electronic properties addition of conductive phase such as carbon during synthesis is required[5]. It is worth noting that not all carbons are equal because they vary in surface area (from several m 2/g to over 1000 m2/g) and bond type (sp2, sp3 or even sp)[6]. Therefore, the selection of conductive carbon is important for the electrochemical performance of the cells containing LiMnPO4. Aim of Study: The overall aim is to improve the electrochemical performance of LiMnPO4 cathode material synthesised by a novel sol-gel method developed at UWS. The specific aims are: 3. To improve the electronic conductivity of the materials by addition of conductive carbons; single type or combination of two different carbon types. 4. To investigate the Li+ diffusion rates. Methods: Two broad strategies will be employed to address the diffusion rate and electronic conductivity issues; one is the reduction of the LiMnPO4 particle size to a nanometre level which would consequently lead to a reduction in the diffusion pathway, both for electrons and Li+ in the phosphate structure. The other strategy is to manufacture LiMnPO4 particles coated with a conductive phase, such as carbon that improves the electronic contact between the crystallites. Sample preparation: Three LiMnPO4 samples containing, 5, 10 and 20 wt % conductive carbons will be prepared according to sol-gel methodology developed at UWS [7]. The methodology allows for easy mixing with carbons during the sol-stage of the sol-gel process and therefore is expected to result in a composite cathode material with improved homogeneity than methods based on solid-state reactions. Characterisation: The samples will be characterised by Calorimetry, Electron Microscopy, Raman and Infrared spectroscopies, X-ray diffraction and Surface area measurements. Electrochemical investigations: Selected samples will be used to prepare Li-battery cathodes which will be used to assemble Li-batteries. The electrochemical performance of the batteries will be investigated by Cyclic Voltammetry 210 and charge/discharge cycling using different charge/discharge rates and electrochemical impedance spectroscopy. Form the electrochemical data the energy densities will be calculated and the Li+ diffusion rates will be estimated. Ethics Application Requirements: N/A Note: Because of the commercial sensitivity of the project the successful Hons applicant will be required to sign a UWS Deed of Assignment. The Deed of Assignment creates important legal obligations in relation to: ownership of intellectual property and non-disclosure agreement. Acknowledgements: The project is part of the activities funded by Australia-India Strategic Research Fund grant (ST060005) and a several UWS and SSH research and infrastructure grants. Key References: [[1] N. Recham, Chem. Mater., 21 (2009) 1096-1107. [2] K. Zaghib, A. Mauger, F. Gendron, C.M. Julien, Ionics, 14 (2008) 271-278. [3] T. Shiratsuchi, S. Okada, T. Doi, J.-i. Yamaki, Electrochimica Acta, 54 (2009) 3145-3151. [4] S.K. Martha, B. Markovsky, J. Grinblat, Y. Gofer, O. Haik, E. Zinigrad, D. Aurbach, T. Drezen, D. Wang, G. Deghenghi, I. Exnar, Journal of The Electrochemical Society, 156 (2009) A541-A552. [5] A. Yamada, S. Chung, K. Hinokuma, J. Electrochem. Soc., 148 (2001) A224-A229. [6] A. Milev, D.M.A.S. Dissanayake, G.S.K. Kannangara, A.R. Kumarasinghe, Physical Chemistry Chemical Physics, 15 (2013) 16294-16302. [7] A.S. Milev, G.S.K. Kannangara, B. Ben-Nissan, M.A. Wilson, J. Phys. Chem. B, 108 (2004) 5516-5521. 211 Title of Project: Synthesis of Donor-Doped Strontium Titanate Thin Films (FOR Code/s): 091205 Supervisor: Dr Leigh Sheppard Contact: [email protected] Co-supervisor: Dr Richard Wuhrer Contact: [email protected] Location of Project: Hawkesbury and Parramatta Project Background Strontium titanate (SrTiO3) has recently emerged as an important material for the development of efficient thermoelectric devices. Among a diverse range of applications, these devices, which convert heat into electricity and vice versa, have a growing role in the utilisation of waste heat during industrial processes. As such, thermoelectrics are expected to play a large role in reducing the demand for fossil fuel derived energy and the associated impact of carbon emissions on the environment. A key aspect in the design of a thermoelectric material, is a consideration of the Figure of Merit, which relates the electrical conductivity of the material to its thermal conductivity. The goal is to develop a material that exhibits high electrical conductivity while maintaining low thermal conductivity. Both of these properties are fundamental to any given material and as such are highly sensitive to how the material has been synthesised and any subsequent processing. Aim of Study: The aim of this study is to identify the impact of processing parameters on the synthesis of donor-doped SrTiO3 thin films with controlled composition and microstructure. Methods: The donor-doped SrTiO3 studied in this project will be synthesised using several techniques that will combine to yield 2 categories of thin films; sputtered films, and hydrothermally grown films. These two categories are very different and require unique experimental parameters to be controlled in order grow a film. As such, they will yield films with unique and potentially very novel characteristics. Initially, the sol-gel technique will be utilised to synthesize SrTiO3 powder with controlled doping levels. This powder will subsequently be pressed and sintered into bulk SrTiO3, leading to 1) customised ceramic targets for magnetron sputtered thin films, and 2) customised ceramic templates for hydrothermally grown of thin films. After these films have been processed, and at selected times during synthesis, samples will be characterised for their composition, morphology, and phase structure using the facilities at the Advanced Materials Characterisation Facility (Parramatta). This will provide the necessary information to understand the role played by different experimental parameters and enable relationships to be established between the selection of key parameters and the resulting film characteristics. Ethics Application Requirements: Nil Key References: K. Kuomoto et al., “Thermoelectric Ceramics for Energy Harvesting”, J. Am. Ceram. Soc., 96, (2013) 1-23 H. Ohta et al., “Giant Thermoelectric Seebeck Coefficient of a Two-Dimensional Electron gas in SrTiO3”, Nature Mats., 6 (2007) 129-134 G. J. Snyder et al., “Complex Thermoelectric Materials”, Nature Mats., 7, (2008) 105-114 H. Xu et al., “Preparation of Shape Controlled SrTiO3 Crystallites by Sol-Gel Hydrothermal Method”, J. Cryst. Growth, 292 (2006) 159-164 S. H. Nam et al., “Characterisation of SrTiO3 Thin Films Prepared by RF Magnetron Sputtering”, J. Phys. D: Appl. Phys., 25 (1992) 727-729 212 Title of Project: High Density Titanium Dioxide for Solar Applications (FOR Code/s): 091205 Supervisor: Dr Leigh Sheppard Contact: [email protected] Co-supervisor: Dr Richard Wuhrer Contact: [email protected] Location of Project: Hawkesbury and Parramatta Project Background Titanium dioxide, TiO2, has emerged as an important material for the efficient harvesting of solar energy for alternative fuel generation (hydrogen) and water decontamination. This is due to its photosensitivity, outstanding corrosion resistance, and low cost. However, TiO2 also exhibits a broad range of functional properties of which not all are favourable for solar energy conversion. The Solar Energy Technologies research group seeks to understand how the properties of TiO2 can be tailored for best practical performance through the appropriate control of fundamental processing parameters. Aim of Study: This project is aimed at establishing a processing route that yields highly dense TiO2 from loose TiO2 powder. This will be achieved by investigating the influence of controlled processing variables, such as temperature, gas phase composition and time, on the microstructure of TiO2 powder compacts. Methods: Students undertaking this project will learn about the development of advanced ceramics and their engineering for solar applications. Students will also gain experience and skills with the use of advanced instrumentation for materials characterisation, particularly scanning electron microscopy and x-ray diffraction, in addition to the tools associated with the forming and fabrication of oxide-based semiconductors. Ethics Application Requirements: Nil Key References: L. Sheppard and J. Nowotny, “Materials for Photoelectrochemical Energy Conversion”, Advances in Applied Ceramics, 106 (2007) 9-20 213 Title of Project: Novel Semiconducting Thin Films for Solar Applications (FOR Code/s): 091205 Supervisor: Dr Leigh Sheppard Contact: [email protected] Co-supervisor: Dr Richard Wuhrer Contact: [email protected] Location of Project: Hawkesbury and Parramatta Project Background Titanium dioxide, TiO2, has emerged as an important material for the efficient harvesting of solar energy for alternative fuel (hydrogen) generation and water decontamination. This is due to its photosensitivity, outstanding corrosion resistance, and low cost. However, TiO2 also exhibits a broad range of functional properties, of which not all are favourable for energy conversion. The Solar Energy Technologies research group seeks to understand how the properties of TiO2 can be tailored for best practical performance through the appropriate control of processing parameters. Aim of Study: This project is aimed at establishing a deposition protocol for the preparation of doped TiO2 thin films that exhibit high sensitivity to sunlight. Using reactive magnetron sputtering, an advanced technique for the deposition of thin film semiconductors, Ti, O2 and various light-sensitive elements will be combined to form a novel TiO2-based compounds that is sensitive to the visible portion of the solar spectrum. Methods: Students undertaking this project will learn about the fabrication of advanced thin film materials using reactive magnetron sputtering. They will also gain experience with the use of advanced instrumentation for materials characterisation, including scanning electron microscopy and x-ray diffraction. Ethics Application Requirements: Nil Key References: L. Sheppard and J. Nowotny, “Materials for Photoelectrochemical Energy Conversion”, Advances in Applied Ceramics, 106 (2007) 9-20 214 Title of Project: Synthesis and Characterisation of Pyrophosphate-Nanocarbon Composite for Next Generation LiBatteries (FOR Code/s): 0303 and 0912 Supervisor: Dr Adriyan Milev Email: [email protected] Telephone: x9945 Co-supervisor: A/Prof Kamali Kannangara Email: [email protected] Telephone: x9952 Co-supervisor: Dr Laurel George Email: [email protected] Telephone: x9976 Location of the Project: Parramatta North Project Background Since the commercialization of lithium-ion batteries in the 1990s, they have undergone intensive scientific research and successful applications in a variety of portable electronic devices. The oxide-based materials; LiCoO2, LiNiO2, and the spinel LiMn2O4; and all their substituted variations have been extensively studied and used as positive electrode materials. However, current electrode materials face limitations, in terms of specific energy and energy density, and a cathode material with high energy density is greatly sought. Increasing the specific energy can be achieved by using electrodes with higher voltage than the existing cathodes but keeping the voltage in the range of existing electrolytes. Recently, the possibility to use pyrophosphates, Li2MP2O7 (M = Fe, Mn, Co), as cathode materials has been discussed [1-3]. Pyrophosphates thus deliver the unique capability to realize the highest M3+/M2+ redox activity among all polyanionic cathodes[4]. It is even more impressive owing to the absence of highly electronegative and/or F- anions, which make the cathodes thermally/chemically unstable. The increment in redox potential is s significant in the case of Mn-compounds, with Li2MnP2O7 offering much a high redox potential (4.45 V), which is still in the safe operational window of current generation organic electrolytes. Thus, it appears that the lithium transition metal pyrophosphates can be considered as having a potential for a generation of new cathode materials. Due to its poor electronic properties addition of conductive phase such as carbon during synthesis is required[5]. It is worth noting that not all carbons are equal because they vary in surface area (from several m 2/g to over 1000 m2/g) and bond type (sp2, sp3 or even sp)[6]. Therefore, the selection of conductive carbon is important for the electrochemical performance of the cells containing Li2MP2O7. Aim of Study: The overall aim is to improve the electrochemical performance of pure Li 2FeP2O7, Li2MnP2O7 and mixed transition metal pyrophosphate Li2Fe0.5Mn0.5P2O7 cathode material synthesised by a novel sol-gel method developed at UWS. The specific aims are: 5. To improve the electronic conductivity of the Li2MP2O7 cathode materials by addition of 20 wt % carbon black. 6. To investigate the Li+ diffusion rates as function of Li2MP2O7 crystallite sizes and surface areas. Methods: Two broad strategies will be employed to address the diffusion rate and electronic conductivity issues; one is the reduction of the Li2MP2O7 particle size to a nanometre level which would consequently lead to a reduction in the diffusion pathway, both for electrons and Li+ in the phosphate structure. The other strategy is to manufacture Li2MP2O7 particles coated with a conductive phase, such as carbon that improves the electronic contact between the crystallites. Sample preparation: Three Li2MP2O7 samples containing 20 wt % conductive carbon black will be prepared according to sol-gel methodology developed at UWS [7]. The methodology allows for easy mixing with carbons during the solstage of the sol-gel process and therefore is expected to result in a composite cathode material with improved homogeneity than the existing methods. The crystal and particle sizes of the Li2MP2O7 -carbon composites will be manipulated by; (1) temperature and time and by (2) ball-milling, post synthesis of the material. Characterisation: The samples will be characterised by Calorimetry, Electron Microscopy, Raman and Infrared spectroscopies, X-ray diffraction and Surface area measurements. 215 Electrochemical investigations: Selected samples will be used to prepare Li-battery cathodes which will be used to assemble real Li-batteries. The electrochemical performance of the batteries will be investigated by Cyclic Voltammetry and charge/discharge cycling using different charge/discharge rates and electrochemical impedance spectroscopy. Form the electrochemical data the energy densities will be calculated and the Li+ diffusion rates will be estimated. Ethics Application Requirements: N/A Note: Because of the commercial sensitivity of the project the successful Hons applicant will be required to sign a UWS Deed of Assignment. The Deed of Assignment creates important legal obligations in relation to: ownership of intellectual property and non-disclosure agreement. Acknowledgements: The project is part of the activities funded by Australia-India Strategic Research Fund grant (ST060005) and a several UWS and SSH research and infrastructure grants. Key References: [[1] L. Adam, A. Guesdon, B. Raveau, J. Solid State Chem., 181 (2008) 3110. [2] H. Zhou, S. Upreti, N.A. Chernova, G. Hautier, G. Ceder, M.S. Whittingham, Chemistry of Materials, 23 (2010) 293300. [3] S.-i. Nishimura, R. Natsui, A. Yamada, Dalton Transactions, 43 (2014) 1502-1504. [4] A. Gutierrez, N.A. Benedek, A. Manthiram, Chemistry of Materials, 25 (2013) 4010-4016. [5] A. Yamada, S. Chung, K. Hinokuma, J. Electrochem. Soc., 148 (2001) A224-A229. [6] A. Milev, D.M.A.S. Dissanayake, G.S.K. Kannangara, A.R. Kumarasinghe, Physical Chemistry Chemical Physics, 15 (2013) 16294-16302. [7] A.S. Milev, G.S.K. Kannangara, B. Ben-Nissan, M.A. Wilson, J. Phys. Chem. B, 108 (2004) 5516-5521. 216 Technology Including: Medical Biotechnology 217 Medical Biotechnology 218 Title of Project: A pluripotent stem cell model of Myotonic Dystrophy-affected skeletal muscles. (FOR Code/s): 100404 Regenerative Medicine (incl. Stem Cells and Tissue Engineering) Supervisor: Dr Michael O’Connor Contact: M.O'[email protected] Co-supervisor: Dr Leslie Caron Contact: [email protected] Location of Project: Genea Biocells, Sydney Project Background: Myotonic muscular dystrophies (DM) is the most common inherited muscular dystrophy in adults, mainly characterized by muscle wasting and delayed relaxation after muscle contraction (myotonia). The disease is nevertheless pleiotropic and affects a number of other organs and functions, specifically the central nervous system (CNS). The disease is due to an inherited unstable expansion of CTG triplet repeats located within the DMPK gene (DM type 1, or DM1) or a tetranucleotide CCTG expansion in the ZNF9 gene (DM2). Currently, our knowledge of the pathogenesis of the disease is limited and to date, no treatment specifically targets DM. Developing human cellular models for DM is critical not only for understanding the molecular mechanism of the disease but can also have a significant impact on the development of new therapies. Due to their plasticity and unlimited capacity to proliferate, human embryonic stem cells (hESCs) potentially represent a renewable source of skeletal muscle cells (SkMCs) and provide an alternative to invasive patient biopsies. We developed a robust and efficient monolayer system to differentiate hESC into mature SkMCs, achieving 70% differentiation efficiency after 26 days without cell sorting or genetic manipulation. In the proposed project this process will be used together with existing human embryonic stem cell lines to investigate a stem cell model of DM. Aim of Study: Our aim is to develop cellular models for DM1+2 by using pluripotent stem cell lines derived from embryos characterized during preimplantation genetic diagnosis as carriers of the disease. We will study the development, phenotype and function of DM1+2 muscles compared to normal controls to identify new cellular mechanisms underlying DM as well as readouts suitable for the development of a phenotypic high-content drug screening assay. Methods: Human embryonic stem cell lines carrying DM1 and DM2 as well as normal controls were expanded and characterised at Genea Biocells. These cells will be differentiated to skeletal muscle using our efficient monolayer system. The development will be monitored by immunofluorescence staining for muscle-specific markers using highcontent analysis. The morphology of the resulting myotubes will be quantitatively analysed using high-content analysis and a functional analysis will be carried out using multi-electrode array technology (MEA). RNA will be extracted from DM muscle and normal controls and will be analysed by either microarrays or RNAseq to study disease mechanisms at a molecular level. Putative marker genes will be further investigated by qPCR or immunofluorescence. Ethics Application Requirements: n/a Key References: Timchenko, L. (2013). Molecular mechanisms of muscle atrophy in myotonic dystrophies. The International Journal of Biochemistry & Cell Biology, 45(10), 2280–2287. doi:10.1016/j.biocel.2013.06.010. Rajamohan, D., Matsa, E., Kalra, S., Crutchley, J., Patel, A., George, V., & Denning, C. (2012). Current status of drug screening and disease modelling in human pluripotent stem cells. BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology, 1–18. doi:10.1002/bies.201200053. Bradley, C. K., Scott, H. A., Chami, O., Peura, T. T., Dumevska, B., Schmidt, U., & Stojanov, T. (2011). Derivation of Huntington’s Disease-Affected Human Embryonic Stem Cell Lines. Stem Cells and Development, 20(3), 495–502. doi:10.1089/scd.2010.0120. 219 Medical & Health Sciences Including: Medical Biochemistry & Metabolomics Clinical Sciences Complementary & Alternative Medicine Human Movement & Sports Sciences Immunology Medical Microbiology Neurosciences Oncology & Carcinogenesis Paediatrics & Reproductive Medicine Medical Physiology Public Health & Health Science Other Medical & Health Sciences 220 Medical Biochemistry & Metabolomics 221 Field of Research: Molecular Physiology / Neuroscience (FOR Code/s): 1109, 0606, 1101, 0601 Title of Project: Defining Molecular Mechanisms Underlying Multiple Sclerosis Supervisor: Prof. Jens Coorssen Email: [email protected] Co-supervisor: Dr. Simon Myers Email: [email protected] Campus project is offered and conducted: Campbelltown Telephone: 46203802 Telephone: 46203383 Background (max 500 words) Multiple Sclerosis (MS) is a CNS disorder of as yet undefined aetiology. It has long been assumed to be an autoimmune disorder, and there is no doubt that such a component is an active part of the disease process and its progression. Nonetheless, it has also become apparent that this aspect alone does not necessarily explain the initiation/development of MS; a newer hypothesis holds that MS may first and foremost be a degenerative disorder, specifically an oligodendrocytosis. We are currently engaged in a research project to better distinguish between these aspects of MS using different mouse models as well as blood/white cell samples from human patients. The outcomes will be important in terms of enabling earlier and/or better identification of (i) MS patients; (ii) prognostic indicators; and (iii) new therapeutic targets. Aim of Study: Hypothesis – MS is fundamentally a degenerative disease. Aims - Use detailed proteomic or lipidomic analyses to better understand molecular changes occurring in mouse models of MS - Identify specific CNS changes; - Identify specific changes in white cells Specific details for an Honours project can be discussed and refined with a suitable candidate. Methods: We have well established protocols for tissue processing, protein and lipid extraction, and all aspects of (i) proteomic analyses using a refined, quantitative 2D gel approach; and (ii) lipidomic analyses using a refined, quantitative high performance thin layer chromatography approach. Ethics Application Requirements: Both human (hospital) and animal ethics approval are in place. 222 Field of Research: Molecular Physiology / Proteomics (FOR Code/s): 0601, 1101 Title of Project: Toward Single-Cell Proteomics Supervisor: Prof. Jens Coorssen Email: [email protected] Co-supervisor: Dr. Chandra Malladi Email: [email protected] Campus project is offered and conducted: Campbelltown Telephone: 46203802 Telephone: 46203813 Background We lack fundamental understanding of molecular mechanisms underlying most serious healthcare burdens, or why therapeutics often fail after initially proving effective. Identifying meaningful disease biomarkers and understanding molecular mechanisms demands far more rigorous analyses than provided by many research approaches popularised over the last decade. As proteins are the active players in all cellular functions, alterations in their structure, function, and/or abundance underlie disease states; they are thus the fundamental and rational targets of virtually all drugs. Large-scale, quantitative, and systematic analysis of all the proteins in a sample (i.e. top-down proteomics) offers the most direct path to understanding molecular mechanisms and thus identification of new therapeutic targets and biomarkers. However, a more recently recognised need is for single cell proteomics to understanding clinically critical cell heterogeneities, including those responsible for cancer metastasis. Aim of Study: Over the last several years we have developed a combined and highly refined protocol for sample handing, 2D gel electrophoresis, protein detection, and imaging that yields top-down proteomic analyses of the highest resolution and sensitivity [1-3]. We are now aiming to progressively drive these analyses to the single-cell level through a series of further refinements in combination with other ongoing analytical work in the group. Here we test the hypothesis that simply altering the physical parameters of the resolving gels will enable substantial decreases in the total amount of starting material required for an effective top-down proteomic analysis. Methods: Systematic testing and refinement of alterations in the size and composition of protein resolving gels; this will also likely include developing alternate handling and protein extraction methods more compatible with the analysis of single cells. Preliminary results have established this as a feasible approach. Ethics Application Requirements: not applicable Key References: 1. Wright, E.P., Partridge, M.A., Padula, M.P., Gauci, V.J., Malladi, C.S., and Coorssen, J.R. (2014) Top-down proteomics: Enhancing 2D gel-electrophoresis from tissue processing to high sensitivity protein detection. Proteomics 14, 872-889. 2. Gauci, V.J., Padula, M.P., and Coorssen, J.R. (2013) Coomassie blue staining for high sensitivity gel-based proteomics. Journal of Proteomics 90, 96-106. 3. Wright, E.P., Prasad, K.A.G., Padula, M.P., and Coorssen, J.R. (2014) Deep Imaging: How much of the Proteome does current top-Down technology already resolve? PLoS ONE 9(1): e86058. 223 Field of Research: Molecular Physiology / Proteomics (FOR Code/s): 0601, 1101 Title of Project: Improving Protein Identifications Using Mass Spectrometry Supervisor: Prof. Jens Coorssen Email: [email protected] Co-supervisor: Dr. Chandra Malladi Email: [email protected] Campus project is offered and conducted: Campbelltown Telephone: 46203802 Telephone: 46203813 Background We lack fundamental understanding of molecular mechanisms underlying most serious healthcare burdens, or why therapeutics often fail after initially proving effective. Identifying meaningful disease biomarkers and understanding molecular mechanisms demands far more rigorous analyses than provided by many research approaches popularised over the last decade. As proteins are the active players in all cellular functions, alterations in their structure, function, and/or abundance underlie disease states; they are thus the fundamental and rational targets of virtually all drugs. Large-scale, quantitative, and systematic analysis of all the proteins in a sample (i.e. top-down proteomics) offers the most direct path to understanding molecular mechanisms and thus identification of new therapeutic targets and biomarkers. Such gel-resolved proteins are excellent substrates for proteolytic digestion prior to LC/MS analysis of peptides to then identify (ID) proteins from a number of different databases; ID quality hinges on several criteria, including overall sequence coverage - this is often proportional to the amount of starting material. The issue is how to effectively handle lower abundance proteins that we now routinely detect using our refined proteome analyses. Aim of Study: We have developed a combined and highly refined protocol for sample handing, 2D gel electrophoresis, protein detection, and imaging that yields top-down proteomic analyses of the highest resolution and sensitivity [1-3]. Thus, we routinely detect low abundance proteins that require high quality IDs. What is needed is a systematic evaluation of in-gel protein spot density (i.e. amount of protein) vs. trypsin digestion conditions (i.e. concentration, time, & temperature) to ensure optimal peptide yields and thus high quality protein IDs. Here we test the hypothesis that optimising digestion parameters relative to spot density enables optimal & consistent protein IDs. Methods: Systematic testing and refinement of digestion conditions relative to protein spot density, followed by LC/MS analyses and database searching to ensure the best possible protein IDs. Preliminary results have established this as a feasible approach. Ethics Application Requirements: not applicable Key References: 1. Wright, E.P., Partridge, M.A., Padula, M.P., Gauci, V.J., Malladi, C.S., and Coorssen, J.R. (2014) Top-down proteomics: Enhancing 2D gel-electrophoresis from tissue processing to high sensitivity protein detection. Proteomics 14, 872-889. 2. Gauci, V.J., Padula, M.P., and Coorssen, J.R. (2013) Coomassie blue staining for high sensitivity gel-based proteomics. Journal of Proteomics 90, 96-106. 3. Wright, E.P., Prasad, K.A.G., Padula, M.P., and Coorssen, J.R. (2014) Deep Imaging: How much of the Proteome does current top-Down technology already resolve? PLoS ONE 9(1): e86058. 224 Title of Project: Effect of novel orally active, small molecule cyclic peptide compounds on prostate cancer cells (FOR Code/s): Division 11: Medical and health sciences. Group 1101: Medical Biochemistry and Metabolomics. Supervisor: A/Prof. Kieran Scott Contact: [email protected] Co-supervisor: Dr David Harman Contact: [email protected] Location of Project: Ingham Institute of Applied Medical Research, Liverpool and UWS Mass Spectroscopy Facility, Campbelltown. Project Background. Prostate cancer is the second most common cause of cancer-related death in Western society with over 3000 Australian men dying from this cancer each year, despite improvements in diagnosis and treatment. So there is a need for new approaches to treatment. We have developed small cyclic peptide compounds (called c2 and cF) that slow the growth of prostate tumours in mouse models and in some cases make tumours go away even when treatment is stopped. One of these compounds is close to being tested in human clinical trials. The compounds target an enzyme (hGIIA) in a lipid pathway (the eicosanoid pathway) that produces up to 150 different metabolites of the omega-6 fatty acid arachidonic acid. We think it is important to know how hGIIA affects the production of eicosanoids in prostate cancer cells and how c2 and cF influence this role. This project will help answer these questions. Aim of Study: This project aims to study the role of the eicosanoid pathway in hGIIA function in prostate cancer cells in culture. Methods: Prostate cancer cells (LNCaP, DU145 and PC-3) will be grown in cell culture and treated with or without c2. cF. hGIIA inhibitors in the presence and absence of added hGIIA. Cells will be harvested and the expression level of enzymes in the eicosanoid pathway (e.g. COX-1, COX-2, 5-LOX, 12-LOX, 15-LOX 1 and 2), determined using semiquantitative Western blot analysis. Cell culture media will be harvested and the production of eicosanoids (e.g. PGE2, 5-HETE, 12 HETE and 15 HETE) in the media determined by liquid chromatography/electrospray ionisation tandem mass spectroscopy (LC/ESI-MS/MS). The results will provide important information about the mechanism of action of hGIIA and its inhibitors in prostate cancer cells. Ethics Application Requirements: None. Key References: 1. Scott, K. F., Sajinovic, M., Hein, J., Nixdorf, S., Galettis, P., Liauw, W., de Souza, P., Dong, Q., Graham, G. G., Russell, P. J. (2010). Emerging roles for phospholipase A2 enzymes in cancer. Biochimie 92 : 601- 610 2. Sved, P.* Scott, K. F.,* McLeod, D., King, N.J.C., Singh, J, Tsatralis, T., Nikolov, B., Boulas, J., Nallan, L., Gelb, M.H., Sajinovic, M., Graham, G.G., Russell, P. J., Dong, Q. (2004).Oncogenic Action of Secreted Phospholipase A2 in Prostate Cancer. Cancer Res. 64 : 6934-6940 3. Lawrence K. Lee, Katherine J. Bryant, Romaric Bouveret, Pei-Wen Lei, Anthony P. Duff, Stephen J. Harrop, Edwin P. Huang, Richard P. Harvey, Michael H. Gelb, Peter P. Gray, Paul M. Curmi, Anne M. Cunningham, W. Bret Church, Kieran F. Scott. (2013) Selective inhibition of human group IIA secreted phospholipase A2 (hGIIA) signaling reveals arachidonic acid metabolism is associated with colocalization of hGIIA to vimentin in rheumatoid synoviocytes. J. Biol. Chem. 288:15269-15279. 4. Deems, R., Buczynski, M. W., Bowers-Gentry, R., Harkewicz, R., Dennis, E. A. (2007) Detection and Quantitation of Eicosanoids via High Performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry. Meth. Enzymol. 432:59-82. 225 Clinical Sciences 226 Title of Project: Coordination of downhill walking with and without auditory cueing (FOR Code/s): 110314 (Orthopaedics); 110317 (Physiotherapy); 110321 (Ecl. Physiotherapy); 110601 (Biomechanics); 110603 (Motor Control) Supervisor: Associate Professor Jack Crosbie Contact: [email protected] Co-supervisor: Dr. Amitabh Gupta Contact: [email protected] Location of Project: School of Science and health, Campbelltown campus (24.3.115) Project Background The purpose of this study is to explore the relationships between segmental movements (in three dimensions) during walking down level slopes of different inclinations and the effect that feedback has on the technique of walking. The literature on downhill walking is very sparse, particularly in comparison to level walking (or even walking up an incline). However the task of walking downhill is often a challenge, particularly for elderly individuals and younger people with knee pain. Furthermore, the challenge of walking on either a flat or downhill surface is often made more difficult due to a shift in attention such as having to focus on a different task at the same time or in fact perform two tasks synchronously (eg. “walk and talk”). A strategy which has been used to evaluate the dual-task paradigm has been to provide an audible cue during the performance of a motor task to determine changes in movement strategies. This type of augmented feedback requires a shift in focused attention from performing a motor task only, thereby challenging the neuromuscular system to have to adapt and maintain adequate control. There are no reports of any studies considering the changes in coordination and muscle activity in the lower limb during decline walking with a concurrent shift in attentional strategy, however, these represent functional demands commonly encountered and are often reported as problems by people with intrinsic changes due to age or impairment. Aim of Study: The aim of this study is to evaluate the effect of downhill walking on the gait pattern and the effect of audible cueing on the gait pattern. Methods: In this study, a population of healthy young and older participants will be recruited. A target number of 15 people under the age of 35 and 15 over the age of 60 will be tested. Participants will be required to perform a series of short walks at a comfortable speed on a treadmill, both on the flat and at two downward inclines, with and without an audio cue (metronome). Hip, knee and ankle joint kinematics and corresponding muscle activation levels of 6 lower limb muscles will be recorded on one leg using 3D motion capture (Optotrak) electromyography recording (Zerowire) instruments respectively. Dependant variables including joint excursions and muscle activation (amplitude and latency characteristics) will be determined and analysed statistically using standard repeated ANOVA procedures. Ethics Application Requirements: Ethical approval for this study has been granted (HREC Approval Number: H10299). Key References: Baker K, Rochester L, Nieuboer A. The immediate effect of attentional, auditory, and a combined cue strategy on gait during single and dual tasks in Parkinson's disease. Archives of Physical Medicine and Rehabilitation. 2007;88:1593600. Dorfman M, Herman T, Brozgol M, Shema S, Weiss A, Hausdorff JM, et al. Dual-Task Training on a Treadmill to Improve Gait and Cognitive Function in Elderly Idiopathic Fallers. Journal of Neurologic Physical Therapy. 2014. 227 Title of Project: Gastrointestinal motility (FOR Code/s): 110307 Gastroenterology and Hepatology Supervisor: Dr Vincent Ho Contact: [email protected] Co-supervisor: Dr Jerry Zhou Contact: [email protected] Location of Project: Campbelltown Project Background We are discovering the factors that influence gastrointestinal (GI) motility at the School of Medicine. We welcome innovative students interested in participating in an exciting multi-disciplinary research program that blends clinical medicine, molecular biology and food science. Dr Vincent Ho’s research uses a range of technologies to investigate the physiological and molecular properties of the GI tract. The human body relies on the multifaceted functions of the GI tract to process ingested food, assimilate water and nutrients, and eliminate waste. This involves multiple levels of regulatory cells and mechanisms to generate normal coordinated movement. Despite the importance of GI motility, remarkably little is known about the complex and dynamic influences of factors, such as ageing, chronic diseases, polypharmacy and diet, have on GI motility. Our laboratory is involved in two research streams in the field of GI motility: clinical and basic science. The clinical research has shown an increase in the prevalence of motility disorders associated with several factors. We plan to investigate the causes of these trends through this proposed study. Our translational research aims to convert discoveries from the laboratory into real-word benefits that can be implemented in our GI Motility Clinics at Camden Hospital and Blacktown Clinical School. We now seek Honours students interested in participating in discovering the mechanisms of GI motility and the factors that influence its behaviour. Aim of Study: Investigate the physiological and molecular properties of GI motility: - Polypharmacy mouse model - Aging mouse model - Chronic diabetic pig model - Dietary changes Methods: Gastrointestinal motility monitor – an organ bath system used to maintain and monitor gastrointestinal organ function outside of the host Immunofluorescence – visualisation of specific regulatory cell populations in the GI tract with targeted antibodies and fluorescent microscopy Rheometer and food texture analyser – quantification of food properties, e.g. viscosity, texture, shear stress Gastrointestinal manometry – evaluation of peristalsis or the presence of dismotility in the GI tract with pressure sensors Development of animal models – work with our collaborators in the development of animal models and surgical removal the specific organs Ethics Application Requirements: Ethics for the mice models have been obtained by our collaborators at the Kolling Institute of Medical Research. Ethics for the pig models are currently awaiting approval as a joint application with our collaborators at Westmead Hospital Key References: 1. Hoffman et. al. Gastrointestinal Motility Monitor (GIMM). J. Vis. Exp. (46), e2435, doi:10.3791/2435 (2010). 2. Chen et. al. Visualization of the Interstitial Cells of Cajal (ICC) Network in Mice. J. Vis. Exp. (53), e2802, doi:10.3791/2802 (2011). 3. Firth and Prather. Gastroinestinal Motility Problems in the Elderly Patient. Gastroenterology 122.6:1688-1700 (2002). 228 Title of Project: When do eating disorders start? How common are DSM-5 eating disorders? What are the sociodemographic correlates and health related burden of eating disorders in the community? (FOR Code/s):110319 Psychiatry 111714 Mental health Supervisor: Prof Hay Contact: [email protected] Co-supervisor: Dr Slewa-Younan Contact: [email protected] Location of Project: not locality dependant Project Background There is evidence that the distribution and determinants of eating disorders in the community is changing with increasing numbers of men and people from disadvantaged backgrounds with eating disorders. This project has potential for the student to also develop their own alternate or additional ideas and questions from previously collected data. Aim of Study: To investigate prevalence and sociodemographic determinants of eating disorders. Methods: A nested study within a large community survey conducted in 2014 with comparative data from 1995, 1998, 2005 and 2008/9 surveys in South Australia. Ethics Application Requirements: HREC is obtained. The student and the nested project will need to be added to current study investigators. Key References: Mitchison, D., Hay, P., Slewa-Younan, S., & Mond, J. (2012). Time trends in population prevalence of eating disorder behaviors and their relationship to quality of life. PloS one, 7(11), e48450. Mitchison D, Hay P, Slewa-Younan S, Mond J.The changing demographic profile of eating disorder behaviors in the community.BMC Public Health. 2014 Sep 11;14(1):943. 229 Title of Project: Health literacy of people with obesity and binge eating. (FOR Code/s):110319 Psychiatry 111714 Mental health Supervisor: Prof Hay Contact:[email protected] Co-supervisor: Dr Slewa-Younan Contact: [email protected] Location of Project: not locality dependant Project Background Binge eating disorders is common in people who are overweight but the problem is under-recognised and undertreated despite the availability of evidence based treatments. Poor health literacy likely contributes to this treatment gap. Aim of Study: To better understand putative reasons for the treatment gap in people with binge eating disorder and obesity. Methods: A nested study is being conducted within a randomised controlled trial for obesity where by health literacy in regards to both binge eating disorder and obesity is being assessed in 100 participants. Ethics Application Requirements: HREC is obtained. The student and the nested project will need to be added to current study investigators. Key References: Mond JM, Hay PJ, Rodgers B, Owen C. (2007). Health service utilization for eating disorders: Findings from a community‐based study. International Journal of Eating Disorders, 40(5), 399-408. Mond JM, Hay PJ. (2008). Public perceptions of binge eating and its treatment. International Journal of Eating Disorders, 41(5), 419-426. Jorm, A F., et al. "Research on mental health literacy: what we know and what we still need to know." Australian and New Zealand Journal of Psychiatry 40.1 (2006): 3-5. 230 Title of Project: When do eating disorders start? How common are DSM-5 eating disorders? What are the sociodemographic correlates and health related burden of eating disorders in the community? (FOR Code/s):110319 Psychiatry 111714 Mental health Supervisor: Prof Hay Contact: [email protected] Co-supervisor: Dr Slewa-Younan Contact: [email protected] Location of Project: not locality dependant Project Background There is evidence that the distribution and determinants of eating disorders in the community is changing with increasing numbers of men and people from disadvantaged backgrounds with eating disorders. This project has potential for the student to also develop their own alternate or additional ideas and questions from previously collected data. Aim of Study: To investigate prevalence and sociodemographic determinants of eating disorders. Methods: A nested study within a large community survey conducted in 2014 with comparative data from 1995, 1998, 2005 and 2008/9 surveys in South Australia. Ethics Application Requirements: HREC is obtained. The student and the nested project will need to be added to current study investigators. Key References: Mitchison, D., Hay, P., Slewa-Younan, S., & Mond, J. (2012). Time trends in population prevalence of eating disorder behaviors and their relationship to quality of life. PloS one, 7(11), e48450. Mitchison D, Hay P, Slewa-Younan S, Mond J.The changing demographic profile of eating disorder behaviors in the community.BMC Public Health. 2014 Sep 11;14(1):943. 231 Title of Project: The Effect of Toe Deformities on Sonographer Interpretation of Metatarsophalangeal Joint Effusions (FOR Code/s): Division: 11 (Medical and Health Sciences) Group: 1103 Clinical Sciences Field: 110318 Podiatry; 110320 Radiology & Organ Imaging; 110322 Rheumatology and Arthritis; 110317 Physiotherapy Supervisor: Dr Lisa Newcombe Contact: [email protected] Co-supervisor: TBC Contact: TBC Location of Project: UniClinic (Podiatry Clinic), Building 24, School of Science and Health, Campbelltown Campus, UWS Project Background: Due to the anatomical complexities of the foot and ankle, joint and soft tissue pathologies can often be misdiagnosed when relying on clinical and radiological assessment alone. High resolution ultrasound (HRUS) has been found to be more beneficial in the diagnosis of foot and ankle pathologies(1) with advantages including increased accessibility and affordability, excellent spatial resolution, non-invasive scanning, a lack of ionising radiation, no known adverse side effects, minimal patient discomfort and real-time dynamic scanning opportunities. The advantages of HRUS are countered by the relative operator dependency, reliant on both the skill of the examiner and the technical conditions of the examination and the inter-observer reliability has been questioned(2,3). In the foot, standardisation of HRUS assessment is particularly limited and sonographer technique is often challenged when assessing common foot and ankle deformities(1,4). HRUS assessment of common lesser toe deformities (i.e. claw toes, hammer toes) is currently inconsistent between sonographers due to limitations in available guidelines(5,6,7,8). Discrepancies, therefore, exist between sonographers when assessing metatarsophalangeal joints (MPJs) involved in toe deformities, as sonographers may choose to scan in either a corrected or non-corrected position(6,9). The impact of scanning MPJs in different toe positions on the diagnosis and interpretation of common joint pathologies, including joint effusions, is largely unknown. Furthermore, our understanding of the overall impact of common toe deformities on the level of “normal” joint effusions present in healthy MPJs is limited (4,10,11). This may have important clinical implications for treatment decision-making(12,13,14). To improve standardisation of HRUS assessment of the foot, therefore, this study aims to 1) investigate if toe deformities have an impact on MPJ effusions and 2) determine if different sonographer techniques for assessing toe deformities has an influence over the interpretation of MPJ effusions. Aim of Study: This study aims to determine the impact of 1) toe deformities on ultrasound assessment of MPJ effusions and 2) different sonographer techniques on the level of MPJ effusions when assessing toe deformities using ultrasound. Methods: A consecutive sample of healthy volunteers will be recruited from staff and students in the School of Science of Health, University of Western Sydney. Subjects will be screened for the presence of flexible lesser toe deformities and recruited into two groups. Group A will include subjects with flexible toe deformities & Group B will include subjects without toe deformities. Using a portable GE HRUS machine, one sonographer will scan the MPJs of all Group A toe deformities in a corrected and non-corrected position. All Group B MPJs will be scanned in a neutral position. From saved HRUS images, joint effusions will be measured for all toe positions in Group A and B by two independent examiners using both calliper measurements and semi-quantitative scoring measures(10). The relationship between toe positioning of lesser toe deformities during HRUS assessment and level of MPJ effusions will be analysed using paired group statistical testing for both semi-quantitative scores (ordinal/interval data) and effusion measurements in mm (numerical data) between corrected and non-corrected MPJs in Group A subjects. The impact of toe deformities on the level of MPJ effusions will be analysed using independent group testing will be undertaken for 1) Group A non-corrected MPJs and Group B neutral MPJs and 2) Group A corrected MPJs and Group B neutral MPJs for both semi-quantitative scores (ordinal/interval data) and effusion measurements in mm (numerical data). Ethics Application Requirements: Ethical approval will be required from the School of Science and Health, University of Western Sydney, Research Ethics Committee. Key References: 1) Delle Sedie, A., Riente, L. & Bombardieri, S. 2008, "Limits and perspectives of ultrasound in the diagnosis and management of rheumatic diseases", Modern Rheumatology, vol. 18, no. 2, pp. 125-131 2) Grassi, W., Filippucci, E., Farina, A. & Cervini, C. 2000, "Sonographic imaging of tendons", Arthritis & Rheumatism, vol. 43, no. 5, pp. 969-976.s 3) Wakefield, R., Freeston, J., O'Connor, P., Reay, N., Budgen, A., Hensor, E., Helliwell, P., Emery, P. & Woodburn, J. 2008, "The optimal assessment of the rheumatoid arthritis hindfoot: a comparative study of clinical examination, ultrasound and high field MRI", Annals of the Rheumatic Diseases, vol. 67, no. 12, pp. 1678-1682. 232 4) Lerch, K., Borisch, N., Paetzel, C., Grifka, J., Hartung, W. 2005. Proposal for a sonographic classification of target joints in rheumatoid arthritis. Rheumatology International. 25, 215-219. 5) Backhaus, M., Burmester, G-R., Gerber, T., Grassi, W., Machold, K, P., Swen, W, A., Wakefield, R, J., Manger, B. 2001. Guidelines for Musculoskeletal Ultrasound in Rheumatology. Annals of Rheumatic Diseases: 60, 641-649. 6) Riente, L., Sedie, A, D., Iagnocco, A., Filippucci, E., Meenagh, G. Valesini, G., Grassi, W., Bombardieri, S. 2006. Ultrasound imaging for the rheumatologist V. Ultrasonography of the ankle and foot. Clinical and Experimental Rheumatology. 24: 493-498. 7) McNally, E, G., 2008. Ultrasound of the small joints of the hands and feet: current status. Skeletal Radiology. 37, 99113. 8) Ansede, G., Lee, J, C., Healy, J, C., 2010. Musculoskeletal sonography of the normal foot. Skeletal Radiology, 39, 225-242. 9) Koski, J, M. 1990. Ultrasonography of the metatarsophalangeal and talocrural joints. Clinical Exp Rheumatol. 8: 347351. 10) Szkudlarek, M., Narvestad, E., Klarlund, M. Court-Payen, M., Thomsen, H, S., Ostergaard, M. 2004. Ultrasonography of the Metatarsophalangeal Joints in Rheumatoid Arthritis. Arthritis & Rheumatism. 50 (7); 21032112. 11) Scheel, A, K., Schmidt, W, A., Hermann, K, G. et al. 2005. Inter-observer reliability of rheumatologists performing musculoskeletal ultra-sonography: results from a EULAR “Train the trainers” course. Annals of Rheumatic Diseases. 64: 1043-1049. 12) Green, M, Marzo-Ortega R, J., Wakefield, R, J., Astin, P., Proudman, S., Conaghan, P, G., Hordon, L., Emery, P. 2001. Predictors of outcome in patients with oligoarthritis: results of a protocol of intraarticular corticosteroids to all clinically active joints. Arthritis and Rheumatism. 4, 1177–1183. 13) Bruyn, G, A, W. & Schmidt, W, A., 2009. How to perform ultrasound guided injections. Best Practice Research Clinical Rheumatology, 23, 269-279. 14) D’Agostino MA, Ayral X, Baron G, Ravaud P, Breban M, Dougados M. Impact of Ultrasound Imaging on Local Corticosteroid Injections of Symptomatic Ankle, Hind-, and Mid-Foot in Chronic Inflammatory Diseases. Arthritis & Rheumatism (Arthritis Care & Research 2005; 53: 284–292. 233 Field of Research: Title of Project: 0204 1103 1112 0306 MRI-based Electron Density Mapping for Radiotherapy Treatment Planning Supervisor: Prof William S Price Email: Co-supervisor: Dr Stephen Bosi (UNE) Email: [email protected] Telephone: 4620 3336 Telephone: Other members of the Nanoscale Research Group Campus project is offered and conducted: Campbelltown Background (max 500 words) Radiation therapy is a recommended treatment for approximately half of cancer cases [Delaney et al 2005]. Accurate planning of radiation dose requires both a picture of a patient's tissues and a map of the "electron density" of these tissues, currently obtained using CT (or "CAT") scans which use ionising radiation. At present an electron density (ED) map derived from a CT of the patient is the minimum requirement for treatment planning (TP) for external beam radiotherapy. Magnetic resonance imaging (MRI) scans actually provide a clearer tissue image than CT scans (and without using ionising radiation), but traditional medical MRI methods cannot provide a density map – at least not at the present time. Development of a new method which allows MRI to be used to measure tissue composition AND density would eliminate the extra radiation dose of a CT scan and streamline treatment planning. (Would suit students interested in Biology/Chemistry/Medical Physics/NMR) Aim of Study: The aim is to develop a method allowing MRI scanners to provide a tissue density map which is required for accurate radiation dose planning for radiation therapy. Methods: MRI Experiments + Analysis Ethics Application Requirements: Not Applicable Key References: 15. Delaney G., Jacob S., Featherstone C. et al. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer 104 1129-1137 (2005). 16. Khan F.M. "The Physics of Radiation Therapy" - 3rd ed., Lippincott & Wilkins. Philadelphia USA, 2003. 17. Wu Y., Reese T.G., Cao H., et al. Bone Mineral Imaged In Vivo by 31P Solid State MRI of Human Wrists J. Magn. Reson. Imaging. 34, 623–633 (2011). This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 234 Title of Project: Using stem cell-derived lens epithelial cells to study primary and secondary cataract. (FOR Code/s): 0601, 1103, 0303, 0301 Supervisor: Dr Michael O’Connor Contact: [email protected] Location of Project: School of Medicine, Campbelltown Campus Project Background: Primary and secondary cataracts in adults, children and babies place a large burden on medical health systems worldwide. Ocular lens surgery is currently the only option to restore vision in these patients, but costs billions of dollars annually around the world. It is therefore clear that anti-cataract drug screening methods need to be developed in order to identify compounds that can inhibit or delay the formation or progression of primary and secondary cataract. Until now, development of such methods has been severely hampered by limited access to normal human lens tissue. Encouragingly, my group recently established a new method for generating pure populations of human lens epithelial cells from pluripotent stem cells. This new source of human lens cells will enable the establishment of methods for high-throughput anti-cataract drug screening. It may also enable regeneration of functional human lenses in vitro, similar to the in vitro regenerated rat lenses previously generated by my group. Such in vitro human lenses could be used for studies of lens and cataract development, toxicology studies of new drugs and cosmetics, and identification of anti-primary cataract drugs. Aim of Study: This study will give students training in key stem cell and regenerative medicine techniques specific to lens and cataract research that are also highly relevant to regenerative medicine approaches to all human tissues. Students will be encouraged to present their work at conferences and publish their findings in peer reviewed journals Methods: Students will be taught widely applicable regenerative medicine techniques including tissue culture maintenance of human pluripotent stem cells, directed differentiation to ocular lens cells, purification of lens epithelial cells, production of lens fibre cells for in vitro human lens regeneration, and application of lens epithelial cells to drug screening. Cell type characterisation will be performed by a range of techniques including flow cytometry, polymerase chain reaction, and high-content imaging. Students considering this project must be comfortable working with human embryonic stem cells before applying. Ethics Application Requirements: Appropriate ethics and biosafety approvals have been obtained for the project. Key References: 7. O’Connor and McAvoy. In vitro generation of functional lens-like structures with relevance to age-related nuclar cataract. Investigative Ophthalmology and Visual Science. 2007. 48(3):1245-52. 8. Yang et al. Efficient generation of lens progenitor cells and lentoid bodies from human embryonic stem cells in chemically defined conditions. FASEB J. 2010. 24(9):3274-83. 9. Murphy and O’Connor. A rapid, simple and efficient method for generating pure populations of lens epithelial cells from human pluripotent stem cells. In preparation. 235 Title of Project: Neuroplasticity, pain and movement (FOR Code/s): 110317; 110321; 110603; 110903 Supervisor: Professor Lucy Chipchase Contact: [email protected] (Phone 4620 3758) Co-supervisor: Contact: Location of Project: BRAiN-Laboratory, School of Science and Health, Campbelltown Campus Project Background The Brain Rehabilitation and Neuroplasticity Unit (BRAiN-U) aims to answer key basic science and clinical questions in the field of neuroplasticity, pain and motor learning. In addition, we aim to develop new brain-based treatments for neurological and musculoskeletal disorders. I am particularly interested, and currently conducting research, in a range of common clinical conditions including acute and chronic pain, anterior knee pain, knee osteoarthritis, and tennis elbow. I am also interested in how brain stimulation and therapeutic techniques can be used to enhance skill acquisition in sport (e.g. golf) and after injury. I have a range of projects available and am also open to discussing your ideas and suggestions for research in this field. Aim of Study: My research priorities are: 1. To understand the way the healthy human brain can change and adapt throughout life through investigation of neuroplastic mechanisms. 2. To understand how neuroplasticity is altered in musculoskeletal (chronic low back pain, osteoarthritis, tennis elbow) disorders. 3. To develop and test new and existing therapies that drive beneficial brain plasticity to alleviate pain and improve function in musculoskeletal disorders 4. To enhance learning in the healthy brain, learning of sports specific skills, re-learning of skills that have been lost through illness or injury, using non-invasive brain stimulation and other therapeutic techniques. Methods: The BRAiN-U laboratory is fully functional with two transcranial magnetic stimulation units, EMG, a neuronavigation system, transcranial direct current, acute pain models, motor learning tasks and quantitative sensory testing units. The methods would be selected based on each project. I have supervised over 20 Honours students, all of whom have achieved first class Honours. Six of these have progressed to PhDs being competitive for scholarships. Currently, our laboratory has a number of Honours and PhD students so you will work in a very engaging environment and have opportunities to gain skills and knowledge in the measurement and analysis of brain plasticity data and other specific measurement tools as well as working and collaborating with a number of research higher degree students and academics. I have a very collegial approach to mentoring and supporting beginning researchers. I aim to ensure that the work you conduct will be presented at conferences and be of a standard to submit for publication. My projects will suit students from a health science program (e.g. physiotherapy, exercise science, medicine) or a biomedical science with a strong drive to succeed and to learn from leaders in the field. Ethics Application Requirements: I have program ethics (#H10184) that covers a wide variety of projects. Amendments for individual projects would need to be sought. Key References: 236 1. 2. 3. 4. 5. 6. 7. Chipchase LS, Schabrun SM and Hodges PW (2011): Corticospinal excitability is dependent on the parameters of peripheral electrical stimulation: a preliminary study. Archives of Physical Medicine and Rehabilitation 92 (9): 1423-1430 [IF 2.284, 10/62 Rehabilitation journals] Chipchase LS, Schabrun SM and Hodges PW (2011): Peripheral electrical stimulation to induce cortical plasticity: a systematic review of stimulus parameters. Invited Review. Clinical Neurophysiology 122: 456-463 [IF 3.406, 46/192 of clinical neurology journals] Schabrun SM and Chipchase LS (2012): Priming the brain to learn: the future of therapy? Manual Therapy 17: 184-186. [IF 1.885, 18/62 Rehabilitation journals) Andrews R, Schabrun SM, Ridding MC, Galea M, Hodges PW and Chipchase LS (2013): Motor electrical stimulation and corticospinal excitability: the effect of application time. Journal of Neuroengineering and Rehabilitation 10: 51 (IF 2.57; 7/63 Rehabilitation journals; 22/79 Biomedical Engineering journals) Schabrun SM, Ridding MR and Chipchase LS (2013): An update on brain plasticity for physical therapists. Physiotherapy Practice and Research 34: 1-8. Adam K, Peters S and Chipchase L (2013): Knowledge, skills and professional behaviours required by occupational therapist and physiotherapist beginning practitioners in work-related practice: a systematic review. Aust J Occ Ther 60: 76-84 [IF 0.677] Chipchase LS, Schabrun SM, Cohen L, Hodges PW, Ridding MC, Rothwell J, Taylor J and Ziemann U (2012): A checklist for assessing the methodological quality of studies using transcranial magnetic stimulation to study the motor system: an international consensus study. Clinical Neurophysiology 123 (9): 1698-1704. [IF 3.406, 46/192 of clinical neurology journals] 237 Title of Project: The effect of chronic electrical stimulation on neuritogenesis. (FOR Code/s): 1109 Neurosciences 1103 Clinical sciences 060199 Biochemistry and Cell Biology not elsewhere classified 920107 Hearing, Vision, Speech and their disorders Supervisor: Dr Cherylea Browne Contact: 4620 3491 - [email protected] Co-supervisor: Dr Jennie Cederholm Contact: [email protected] Location of Project: Translational Neuroscience Facility, the University of New South Wales, and UWS Campbelltown. Project Background The events involved in transmitting sound information are crucial for us to perceive our surrounding environments. Unfortunately, there is a large population of people that suffer from hearing-related disorders, severe hearing loss or were born deaf [1]. The cochlear implant has been designed to stimulate the auditory neurons with electrical energy. The cochlear implant apparatus includes an external receiver, which receives sound information and transmits it to an external processor. The external processor transmits the electrical energy to the cochlear implant array which is positioned inside the cochlea. The signal is transmitted through the electrodes which stimulated the adjacent spiral ganglion neurons. The main issue that arises with cochlear implants is the poor electro-neural interface [2, 3]. The spiral ganglion neurites tend not to grow towards or connect to the implant array. However, it has been shown that spiral ganglion neurites can be encouraged to regenerate and grow in response to molecular therapy (e.g. neurotrophins) [4]. In addition to the efficacy of neurotrophins in restoring cochlear nerve vitality [5, 6], it is evident from several studies that electrical stimulation inherent to the cochlear implant can sustain the spiral ganglion neurons in the absence of neurotrophins [7]. Aim of Study: To determine the effect of chronic electrical stimulation on nerve cell outgrowth (neuritogenesis). Methods: The effect of chronic electrical stimulation on neuritogenesis will be assessed using an in vitro mouse spiral ganglion explant culture system we have developed at the University of New South Wales, Australia, which provides defined charge-balanced pulsed electric fields across the spiral ganglion cells (which is termed an “explant”). Spiral ganglion explants will be collected from young mice cochleae and cultured for two days in a mixture of growth factors. During this time the explant will be chronically stimulated with varying electric currents. Explants will then be processed for immunohistochemistry and will be analysed using a confocal microscope for growth and neurite extension in response to chronic stimulation. Ethics Application Requirements: Animal Ethics Approval applications will be made to the UNSW and UWS Animal Ethics Committees. Key References: 1. Mathers, C., Smith, A., & Concha, M. (2000). Global burden of hearing loss in the year 2000. Global burden of Disease, 18, 1-30. 2. Long, C. J., Holden, T. A., McClelland, G. H., Parkinson, W. S., Shelton, C., Kelsall, D. C., & Smith, Z. M. (2014). Examining the Electro-Neural Interface of Cochlear Implant Users Using Psychophysics, CT Scans, and Speech Understanding. Journal of the Association for Research in Otolaryngology, 1-12. 3. Bierer, J. A., Faulkner, K. F., & Tremblay, K. L. (2011). Identifying cochlear implant channels with poor electrodeneuron interface: electrically-evoked auditory brainstem responses measured with the partial tripolar configuration. Ear and hearing, 32(4), 436. 4. J. L. Pinyon, S. F. Tadros, K. E. Froud, A. C. Y. Wong, I. T. Tompson, E. N. Crawford, M. Ko, R. Morris, M. Klugmann, G. D. Housley, Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear. Sci. Transl. Med. 6, 233ra54 (2014). 5. Wise, A.K., et al., Effects of localized neurotrophin gene expression on spiral ganglion neuron resprouting in the deafened cochlea. Mol Ther, 2010. 18(6): p. 1111-22. 6. Yu, Q., et al., Protection of spiral ganglion neurons from degeneration using small-molecule TrkB receptor agonists. J Neurosci, 2013. 33(32): p. 13042-52. 7. Leake, P.A., G.T. Hradek, and R.L. Snyder, Chronic electrical stimulation by a cochlear implant promotes survival of spiral ganglion neurons after neonatal deafness. J Comp Neurol, 1999. 412(4): p. 543-62. 238 Title of Project: Beliefs about dealing with Posttraumatic Stress Disorder Alone Amongst Refugees (FOR Code/s): 110319: Psychiatry 111714: Mental health Supervisor: Dr Shameran Slewa-Younan Contact: [email protected] Co-supervisor: Sanja Lujic Location of Project: not locality dependant Contact: [email protected] Project Background: Resettled refugees are a particularly vulnerable group (Slewa-Younan, et al 2014). They have very high levels of mental health problems, in particular, trauma-related disorders, but very low uptake of mental health care. Evidence suggests that poor “mental health literacy” (MHL), namely, poor knowledge and understanding of the nature and treatment of mental health problems is a major factor in low or inappropriate treatment-seeking among individuals with mental health problems (Jorm, 2012) . A recent paper (Slewa-Younan, et al submitted) noted that a high level of participants believed that dealing with the problem such as PTSD alone would be helpful (58%). This was almost 10 times greater than number of participants (6%) in the 2011 NSMHLS who endorsed dealing with the problem alone as helpful and indicates an immediate area for improving the mental health education of refugees. Previous research on factors associated with dealing with mental health problems alone have demonstrated associations with the male gender and beliefs the disorder described is self-limiting and due to personal weakness (Jorm et al 2006). Further researchis need in order to examine such associations in refugee samples. Aim of Study: To examine what are the demographic and clinical characteristics of those who believe that dealing with a problem of PTSD alone would be helpful. This would allow for the development of target mental health promotion programs amongst refugees. Methods: Data for this study will be obtained from a community survey of MHL of Iraqi refugees conducted in 2013. Ethics Application Requirements: HREC is obtained. The student and the nested project will need to be added to current study investigators. Key References: Slewa-Younan S, Uribe, M G, Heriseanu A, Hasan T. (2014) A systematic review of post-traumatic stress disorder and depression amongst Iraqi refugees located in Western countries. Journal of Immigrant and Minority Health, In Press, DOI 10.1007/s10903-014-0046-3 Jorm AF, Kelly CM, Wright A, Parslow RA, Harris MG, McGorry PD: Belief in dealing with depression alone: results from community surveys of adolescents and adults. J Affect Disord 2006, 96(1-2):59-65. Jorm, A. F. (2012). Mental health literacy: empowering the community to take action for better mental health. Am Psychol, 67(3), 231-243. doi: 10.1037/a0025957 239 Complementary & Alternative Medicine 240 Title of Project: Decision making in the use of Complementary Medicine (FOR Code/s): 1104 Supervisor: Prof Alan Bensoussan Contact: [email protected] Co-supervisor: Prof Caroline Smith [email protected] Dr Joanne Packer [email protected] Location of Project: Campbelltown Project Background Complementary medicine includes a diverse range of medicines and therapies that are not considered to be core conventional medicine practices or core conventional allied health practices. Conventional medicine is medicine as practiced by registered medical practitioners and by a range of allied health professionals who support conventional medical practice and include physiotherapists, psychologists and registered nurses. ‘Complementary medicine’ in used to describe healthcare practices such as acupuncture, applied kinesiology, aromatherapy, Ayurveda, chiropractic, environmental medicine, herbal medicine, homeopathy, hypnosis, massage, meditation, naturopathy, nutritional therapy, osteopathy, reflexology, Reiki, Shiatsu, yoga among many others. Approximately 2 in 3 Australians regularly use some sort of Complementary medicine, resulting in almost 4 times more being spent on CM (in out of pocket expenses) than on pharmaceuticals each year. Complexity around risk, responsibility and decision-making of medicine are important considerations to target information, expenditure and resources. Therefore an understanding of the decision making processes behind consumers’ use of these medicines is essential to the Australian health care landscape. There is no such current comprehensive information available on decision making around the use of complementary medicines in Australia. Aim of Study: To understand the reasons behind consumers’ preference for using complementary medicine or circumstances around this decision making and the associated cost benefits Methods Following a review of the international literature, a survey on decision making drivers will be designed using the most appropriate tools and techniques. The gap in knowledge will be defined and based on the gap in knowledge a survey will be designed using a survey tool and distributed in electronic and paper format to a cross section of the general public. Data will be analysed using the SPSS statistics package and prepared for publication. Ethics Application Requirements: ‘Low Risk’ Human Ethics approval will be sought from the Human Research Ethics Committee at UWS Key References: 1. Carmady, B., C.A. Smith, and B. Colagiuri, A comparison of decision-making processes for conventional and complementary medicine in cancer patients. Complementary Therapies in Clinical Practice, 2013. 19(1): p. 32-35. 2. Conboy, L., S. Patel, T.J. Kaptchuk, B. Gottlieb, D. Eisenberg, and D. Acevedo-Garcia, Sociodemographic determinants of the utilization of specific types of complementary and alternative medicine: An analysis based on a nationally representative survey sample. Journal of Alternative and Complementary Medicine, 2005. 11(6): p. 977-994. 3. Pirotta, M., V. Kotsirilos, J. Brown, J. Adams, T. Morgan, and M. Williamson, Complementary medicine in general practice: A national survey of GP attitudes and knowledge. Australian Family Physician, 2010. 39(12): p. 946-950. 4. Xue, C.C., A.L. Zhang, V. Lin, C. Da Costa, and D.F. Story, Complementary and alternative medicine use in Australia: a national population-based survey. The Journal of Alternative and Complementary Medicine, 2007. 13(6): p. 643-650. 5. Manderson, L., N. Warren, and M. Markovic, Circuit Breaking: Pathways of Treatment Seeking for Women With Endometriosis in Australia. Qualitative Health Research, 2008. 18(4): p. 522-534. 241 Title of Project: Effect of a Standardised Herbal Formulation on Age-related Memory and Cognitive Decline in Mice (FOR Code/s): 1104 Supervisor: A/Prof Dennis Chang Contact: [email protected] Co-supervisor: A/Prof Chun Guang Li Contact: [email protected] Prof Gerald Münch (SoM) [email protected] Location of Project: Campbelltown Project Background Aging increases vulnerability to health problems such as cognitive decline, which can negatively impact on both an individual’s quality of life as well as the economic profile of countries worldwide. Age-related cognitive decline is associated with mild cognitive impairment (MCI), a heterogeneous disorder affecting people’s attention, memory and other cognitive capacity. If unchecked, MCI patients can progress to dementia and other systemic diseases such as depression. In Australia, there will be 1.13 million dementia patients and the total associated cost to the Australian health system may exceed 3% of GDP by 2050.1 SLT (previously known as WNK) is a standardised herbal formulation designed for the treatment of vascular dementia and mixed dementia (Alzheimer’s disease + vascular dementia). A series of pharmacological studies have demonstrated that the herbal formulation significant improved learning and memory functions, pathogenic biochemical parameters in blood and brain tissue, and antioxidant capacity in various experimental dementia models.2-6 This current study will further expand our knowledge on the use of SLT to prevent/slow down age related cognitive decline Aim of Study: This study aims to evaluate the effects of SLT and its individual components on memory and cognitive function in aging mouse model. Methods: Behavioural models in rodent are useful tools in the investigation of changes in memory and neurocognition associated with aging and neurodegenerative disease such as dementia. In the current study, the following behaviour tests will be undertaken to evaluate effects of SLT on learning, memory and neurocognitive function in aged mice: Novel object recognition test: This test is used to evaluate cognition, particularly recognition memory, in rodent models of CNS disorders and/or CNS aging Y maze spontaneous alternation test: This is a behavioural test for measuring spatial memory of rodents in order to explore new environments Open field/activity test: This test measures hyperactivity, exploratory activity, stereotyped rotation, anxiety and memory for context Ethics Application Requirements: Animal ethics approval will be sought before the commencement of the project Key References: 1. Access Economics. Keeping dementia front of mind: incidence and prevalence, Canberra 2009. 2. Xu L, Liu JX et al. Effect of Weinaokang (WNK) on dysmnesia in mice model. Journal of Pharmacological and Clinical Chinese Herbal Medicine. 2007; 23:60-61. 3. Xu L, Liu JX, et al. Effects of Weinaokang (WNK) capsule in tracephalic cholinergic system and capability of scavenging free radicals in chronic cerebral hypoperfusion rats. China Journal of Chinese Materia Medica. 2008; 33:531-534. 4. Liu JX, et al. Effect of combination of extracts of ginseng and ginkgo biloba (WNK) on acetylcholine in amyloid beta-protein treated rats determined by an improved HPLC. Acta Pharmacologica Sinica. 2004; 25:1118-1123. 5. Cong WH, Liu JX, et al. Effects of extracts of ginseng and ginkgo biloba on hippocampal acetylcholine and monoamines in PDAPPV7171 transgenic mice. Chinese Journal of Integrated Medicine. 2007; 27:810-813. 6. Zheng YQ, Liu JX, et al. Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Research. 2006; 1138:86-94 242 Title of Project: Effect of complementary medicine formulations on the bioavailability of commercially available and prepared dosage forms (FOR Code/s): 1104 Supervisor: A/Prof Dennis Chang Contact: [email protected] Co-supervisor: Dr Jim Rowe Contact: [email protected] Dr Frank van der Kooy [email protected] Location of Project: Campbelltown Project Background The bioavailability of a bioactive substance whether it be a synthetic drug or complementary medicine from an oral dosage form is defined as the rate and extent of absorption of the bioactive material from the gastrointestinal tract. The factors which affect bioavailability include the physicochemical properties of the drug such as polymorphic form, particle size and crystal habit as these can affect the rate of solution of the active principle in the dosage form and hence the rate and extent of absorption. Formulation factors also can have a significant effect on the rate of solution and hence bioavailability. The choice of excipients is crucial in a given dosage form to ensure the drug is released from the dosage form and is available to be absorbed into the plasma. The same active in different dosage forms (eg tablets, solutions, capsules etc.) can have significantly different bioavailability characteristics which may result in therapeutic failure in the case of low bioavailability or toxic side effects in the case of too high bioavailability. This project would suit a student contemplating a career in Industry either in Production or Regulatory Affairs. Aim of Study: This project will examine various complementary medicine formulations both commercial and prepared and test the bioavailability by standard pharmacopoeia tests such as disintegration and dissolution technology as an indicator of bioavailability Ethics Application Requirements: N/A Key References: 1. A mechanistic Approach to Understanding the Factors Affecting Drug Absorption: A Review of the Fundamentals. Journal of Clinical Pharmacology 2001; 42:620-643. 2. Pharmaceutics: The Science of Dosage Form Design. Ed Aulton ME. 2nd Edition 2002; 234-274. 243 Title of Project: In vitro activity of the Chinese Medicinal Herb, Nao Xin Qing for the treatment of stroke (FOR Code/s): 1104 Supervisor: A/Prof Dennis Chang Contact: [email protected] Co-supervisor: Prof Alan Bensoussan Contact: [email protected] Location of Project: Campbelltown Project Background An aqueous extract of the leaf of the Persimmon tree (Diospyros kaki) prepared as a tea, has featured in the practice of traditional Chinese medicine for centuries [1]. Its widespread use has resulted in the commercial development of Nao Xin Qing (NXQ) tablet containing a standardised extract of the herb. NXQ is widely prescribed for the management of diseases induced by atherosclerosis such as ischemia stroke and coronary heart disease. NXQ extract is reported to possess various pharmacological properties including microbial inhibition, radical scavenging, neuroprotection, blood pressure lowering, as a vasorelaxant, in reducing blood lipids and in thrombosis inhibition. These activities may be at least partially due to the high levels of flavonoids in the herb [2]. Synergism underpins the therapeutic actions of herbal medicine, where patients are generally treated with herbal preparations containing multiple bioactive components or multiple herbs. There is preliminary evidence that complex chemical mixtures enhance therapeutic efficacy by facilitating synergistic action and/or ameliorating/preventing potential side effects [3]. Aim of Study: To assess the antioxidant activity and effect on endothelial dysfunction of the components of the standardised herbal extract, NXQ. To determine the synergistic or additive nature of these components. Methods: In vitro biochemical assays will be used to investigate antioxidant activities of NXQ extract and its key flavonoids components (quercetin and kaempferol) [4]. Total antioxidant activity, free radical and superoxide anion radical scavenging will be determined using. Interactions among the key bioactive components of NXQ will be assessed using the above in vitro assays to assess their synergistic or additive effect mathematically by applying an isobole method [3]. The effect of NXQ on endothelial dysfunction will also be assessed in human endothelial cell line EA.hy926 (Zhou et al., 2012). Ethics Application Requirements: N/A Key References: 1. Xue, Y.-L., T. Miyakawa, Y. Hayashi, K. Okamoto, F. Hu, N. Mitani, K. Furihata, Y. Sawano, and M. Tanokura, Isolation and Tyrosinase Inhibitory Effects of Polyphenols from the Leaves of Persimmon, Diospyros kaki. Journal of Agricultural and Food Chemistry, 2011. 59(11): p. 6011-6017. 2. Xue, Y.L., T. Miyakawa, Y. Hayashi, K. Okamoto, F. Hu, N. Mitani, K. Furihata, Y. Sawano, and M. Tanokura, Isolation and tyrosinase inhibitory effects of polyphenols from the leaves of persimmon, Diospyros kaki. Journal of agricultural and food chemistry, 2011. 59(11): p. 6011-7. 3. Wagner, H., Synergy research: Approaching a new generation of phytopharmaceuticals. Fitoterapia, 2011. 82(1): p. 34-37. 4. Yang, J., J. Guo, and J. Yuan, In vitro antioxidant properties of rutin. LWT - Food Science and Technology, 2008. 41(6): p. 1060-1066. 244 Title of Project: Practising Chinese medicine in non-private practice. (FOR Code/s): 1104 Supervisor: Dr Suzanne Cochrane Contact: [email protected] Co-supervisor: Dr Suzanne Grant Contact: [email protected] Location of Project: Campbelltown Project Background Traditional Chinese medicine (TCM) practitioners in Australia work predominantly in private practice as lone practitioners. There is advocacy within the complementary medicine arena to engage TCM more in integrative medicines. There is a small cohort of practitioners who have experience working in integrated settings – specifically women’s health centres, worker’s health centres and hospitals – and this experience would be useful for health planners and TCM educators to better understand the benefits and dilemmas of working in not-for-profit and/or integrative clinical settings (Baer & Coulter, 2008; Boon, Verhoef, O'Hara, & Findlay, 2004; Hunter, Marshall, Corcoran, Leeder, & Phelps, 2013; Kelner, Wellman, Boon, & Welsh, 2004; Robinson, 2006; Singer & Adams, 2014) Aim of Study: To explore the work experience of TCM practitioners who work in other than private practice settings, focusing particularly on the benefits and dilemmas of working in an integrated team and working with clients who do not pay directly for service. Methods: To locate through professional associations and networks practitioners who have worked in non-private practice settings, design and administer a survey of their views and experiences and undertake in-depth interviews of selected TCM practitioners who work in other than private practice settings. Ethics Application Requirements: Ethics approval is required. Key References: Baer, H., & Coulter, I. D. (2008). Taking stock of integrative medicine: Broadening biomedicine or cooption of complementary and alternative medicine? Health Sociology Review, 17(4), 331-341. Boon, H., Verhoef, M., O'Hara, D., & Findlay, B. (2004). From parallel practice to integrative health care: a conceptual framework. BMC Health Services Research, 4(15). Hunter, J., Marshall, J., Corcoran, K., Leeder, S., & Phelps, K. (2013). A positive concept of health e Interviews with patients and practitioners in an integrative medicine clinic. Complementary Therapies in Clinical Practice, 19, 197-203. Kelner, M., Wellman, B., Boon, H., & Welsh, S. (2004). Responses of established healthcare to the professionalization of complementary and alternative medicine in Ontario. Social Science & Medicine, 59, 915–930. Robinson, N. (2006). Integrated traditional Chinese medicine. Complementary Therapies Clin Pract, 12, 132 - 140. Singer, J., & Adams, J. (2014). Integrating complementary and alternative medicine into mainstream healthcare services: the perspectives of health service managers. BMC Complementary and Alternative Medicine, 14(167). 245 Title of Project: Assessing complementary medicine safety and efficacy related information available on the internet for consumers (FOR Code/s): 1104 Supervisor: Dr Anthony Good Contact: [email protected] Co-supervisor Location of Project: Campbelltown Project Background The use of complementary medicine is widespread in Australia, with reports of up to 80% of Australians consuming a complementary medicine each year [1]. However, the quality of information available on the internet for consumers is questionable, which may pose significant and serious public health concerns. People in the Australian community have the right to be appropriately informed about the safety and efficacy of complementary medicines. The lack of focus on details of efficacy and safety of complementary medicines in the health system leads those who wish to be well informed of the complementary medicines they are taking to seek information elsewhere, which in the information age if most commonly the internet. Health information on the internet ranges from personal accounts of illnesses, consumer discussion groups, chat forums, and advertisements related to products. Aim of Study: This project aims to conduct a preliminary analysis of health regarding the safety and efficacy of complementary medicines available on the internet. Methods Criteria for determining quality of information related to various dimensions such as content, type, scientific merit, ethical aspects with a particular focus on safety and efficacy information will be developed from the literature and applied to analyse the first 50 websites that appear using 'complementary medicine' as a search term for Australian websites. Information gathered from these websites will be compared with published data for those complementary medicines which appear most often on the first 50 websites identified above. Ethics Application Requirements: No HREC approval required as survey work based on published data and not interview data Key References: Bensoussan, A, Meyers, S Towards a safer choice the practice of traditional Chinese medicine in Australia. 1996, Campbelltown, N.S.W.Faculty of Health, University of Western Sydney Macarthur. 476 246 Title of Project: Evaluation of a Yoga program intended as a prevention and/or intervention strategy in disadvantaged groups or groups with restricted resources (FOR Code/s): 1104 Supervisor: Dr Anthony Good Contact: [email protected] Co-supervisor: Prof Alan Bensoussan Contact: [email protected] Location of Project: Campbelltown Project Background The Yoga Foundation (TYF) is a non-profit organisation established to implement yoga-based health promotion programs to improve well-being of communities experience difficulty in their ability to access yoga in the general community. The Foundation’s activities are supported by published evidence of yoga’s effectiveness as a prevention and intervention strategy for people with restricted personal, social or economic resources. Target groups of TYF programs include people with disability, people with mental illnesses, and other groups who experience social disadvantage. At present, TYF is implementing yoga programs for these groups, in partnership with community development organisations in the disability and mental health sectors. These yoga programs aim to improve wellbeing, health and social connections of people in these groups Aim of Study: To work with The Yoga Foundation to develop and implement a framework to systematically evaluate the design, appropriateness and effectiveness of TYF’s intervention programs. Methods: Programs will be evaluated using TYF’s Yoga Program Logic model within a mixed methods framework. This allows for quantitative and qualitative analysis of short, medium and long-term outcomes. The quantitative analysis will define pre- and post- intervention study endpoints which are agreed with program stakeholders prior to initiation of a yoga program. In addition to condition specific endpoints (for example the Hospital Anxiety and Depression Scale (HADS) for interventions targeting depression), Quality of Life measures (such as Personal Wellbeing Index (PWI)), and Goal Achievement measures (such as the Goal Attainment Scale) will be evaluated as endpoints for each program. Structured interviews and focus discussion groups will form the basis of the qualitative analysis. Ethics Application Requirements: An Ethics application will be submitted to the UWS Human Ethics Committee before the commencement of the project Key References: Woolery, A, Myers, H, Sternlieb, B and Zelter, L. “A yoga intervention for young adults with elevated symptoms of depression”, Alternative Therapies 10 no. 2 (2004) 60-63 Khalsa, S.S., Khalsa, G.S., Khalsa, H. K., and Khalsa, M.K. (2008) “Evaluation of a residential Kundalini Yoga Lifestyle Pilot Program for addiction in India”, Journal of Ethnicity in Substance Abuse, vol. 7, no. 1, p. 67-79 Kozasa EH, Santos RF, Rueda AD, Benedito-Silva AA, Ornellas FLDM, Leite JR. EVALUATION OF SIDDHA SAMADHI YOGA FOR ANXIETY AND DEPRESSION SYMPTOMS: A PRELIMINARY STUDY. Psychological Reports 2008,103:271-274. 247 Title of Project: Acupuncture for Cancer-related Symptoms: protocols and safety considerations (FOR Code/s): 1104 Supervisor: Dr Suzanne Grant Contact: [email protected] Co-supervisor: Dr Xiaoshu Zhu [email protected] Location of Project: Campbelltown Project Background Acupuncture is increasingly used in integrative oncology settings for both inpatients and outpatients as an adjunctive treatment for cancer related symptoms in the US and Canada [1] . Some of the symptoms for which acupuncture is used are xerostomia, cancer-related fatigue, nausea and vomiting, pain, diarrhoea, hot flashes, immunosuppression (neutropenia and leukopenia), breathlessness, post-operative ileus, anxiety and depression and chemotherapy induced peripheral neuropathy. An increasing number of clinical trials have been conducted to show the efficacy of acupuncture in the treatment of these symptoms. While these trials are of some use to clinicians there is no synthesis of the actual interventions themselves and provide limited guidance to acupuncturists working in integrative oncology settings. Aim of Study: To create protocols for the acupuncture treatment of cancer-related symptoms and document any safety considerations for specific symptoms. Methods Mixed research methods including literature review and pilot survey will be employed for a design of various protocols in this project. Ethics Application Requirements: N/A Key References: Garcia, M.K., et al., Systematic review of acupuncture in cancer care: a synthesis of the evidence. J. Clin Oncol, 2013. 31(7): p. 952-60 248 Title of Project: Integrative Medicine Centres in Australia: How Integrative Medicine Is Being Practiced in Clinical Centres Across Australia (FOR Code/s): 1104 Supervisor: Dr Suzanne Grant Contact: [email protected] Co-supervisor: Prof Alan Bensoussan [email protected] Location of Project: Campbelltown Project Background Integrative healthcare aims to treat the whole person (physical, emotional, energetic, spiritual), using the body’s innate ability to heal itself with a blend of conventional and complementary therapies. Patients are integrating complementary medicine (CM) and allopathic medicine in a variety of ways depending on their condition and their changing beliefs. Patients with chronic illness typically use CM to reduce, avoid or replace conventional medicine, but don’t commonly give up conventional medicine altogether. Patients may start use of CM following a perceived lack of suitable orthodox treatment, or they are driven by a belief that “a combination of CAM and conventional medicine is superior to either approach alone”. In response to this consumer demand, integrative health care centres have emerged. Staff may comprise allopathic doctors, sometimes a practice nurse, and any combination or type of complementary medicine (CM) practitioners. In Australia, literature is sparse and limited to descriptions of single entities. Little known about the level of integration they provide to patients, the main types of patients and conditions they treat. A summary of the types of centres and programs is needed to inform healthcare policy and research, and to be able to understand the potential and limitations of this type of care. Aim of Study: To better understand how integrative medicine is being practiced in Australia, this project aims to map the field. The project will: Describe primary care integrative medicine facilities; Describe the types of patients that are seen and the health conditions that are treated; Identify facilitators and barriers to successful practice of integrative medicine within these primary care facilities Methods Selection of centres: Integrative medicine centres across Australia will be identified through literature search, yellow pages, online investigation and contacting key players and leaders in the integrative medicine field such as the Australian Integrative Medicine Association. Questionnaire design: A survey used to map the IM field in the US will be adapted to suit an Australian context (Horrigan, 2012). Data collection and analysis: All or a selection of these centres will be sent a survey. The survey will be posted or conducted online using a Survey Monkey. An analysis and report of the findings will be published in a peer-reviewed journal. Ethics Application Requirements: An ethics application will be required with UWS Ethics Key References: 1. Coulter, I. D., et al. (2010). "Integrative Health Care Under Review: An Emerging Field." Journal of Manipulative and Physiological Therapeutics 33(9): 690-710. 2. Horrigan, B. J., et al. (2012). Integrative Medicine in America: How Integrative Medicine Is Being Practiced in Clinical Centers Across the United States, The Bravewell Collaborative. 3. Grace, S. and J. Higgs (2010). "Interprofessional collaborations in integrative medicine." J Altern Complement Med 16(11): 1185-1190. 249 Title of Project: Development of analytical methods for characterising the quality of medicinal herbs. (FOR Code/s): 1104 Supervisor: Dr Cheang Khoo Contact: [email protected] Co-supervisor: Contact: Location of Project: Campbelltown Project Background Herbal quality varies greatly and is influenced by factors such as species type, growth conditions, age of plant, time of harvest and post-harvest treatment. Characterising the quality of a herb is not as straightforward as it seems because natural products have complex composition and decisions have to be made as to which chemical(s) should be measured to infer quality, and hence medicinal efficacy. The National Institute of Complementary Medicine (NICM) at UWS has developed a systematic procedure for selecting the analytes that should be monitored to indicate herbal quality. This study will select an herb and study the compositional variability of the herb sourced from different suppliers in the market place. The analyte(s) determined will be chosen using the selection criteria mentioned and the quality of the herb from different sources ranked. Analytical method development might be necessary. Pharmacological testing (for example antioxidant, free radical, scavenging and anti-inflammatory activity) will then be carried out to observe if the activity of the herb correlates with the quality ranking of the herb derived from chemical testing. The results from this study may lead to a refinement of the selection criteria developed by NICM. Aim of Study: To rank the quality of the herb according to its chemical characteristics and to determine if this correlates with its pharmacological ranking Methods: Chemical characterisation by LC-PDA, LC-MS, GC-MS. Pharmacological testing methods. Ethics Application Requirements: N/A Key References: 1 Jeong, SC, Koyyalamudi, sr, Hughes,JM, Khoo,c. Bailey,T, Marripudi, K., Park, JP, Kim, JH, Song, CH. Antioxidant and immunomodulating activities of exo- and endopolysaccharide fractions from submerged mycelia cultures of culinarymedicinal mushrooms. International Journal of Medicinal Mushrooms, 2013;15(3): 251–266 2. Jeong, SC, Koyyalamudi1, SR, Hughes JM, Khoo, C, Bailey, T, Park, JP, Song, CH, Modulation of cytokine production and complement activity by biopolymers extracted from medicinal plants. Phytopharmacology, 2013, 4(1), 19-30 3. Patricia, D, Sang Chul Jeong SC, Lee, S, Khoo, C, and Koyyalamudi, SR, Antioxidant and anti-inflammatory activities of selected medicinal plants and fungi containing phenolic and flavonoid compounds. Chinese Medicine 2012; 7:26:1 9 4. Lee S, Khoo CS, Pearson JL, Hennell JR, Bensoussan A. Liquid chromatographic determination of narirutin and hesperidin in Zhi Ke in the form of the raw herb and of the dried aqueous extract. Journal of AOAC International. 2009; 93(3): 789-796. 5. Lee S, Khoo C S, Hennell JR, Pearson JL, Jarouche M, Halstead CW, Bensoussan. A.LC determination of albiflorin and paeoniflorin in Bai Shao (Paeonia lactiflora) as a raw herb and dried aqueous extract.Journal of AOAC International. 2009; 92(4):1027-34. 6. Hennell JR, Lee S, Khoo CS, Gray MJ, Bensoussan A. The determination of glycyrrhizic acid in Glycyrrhiza uralensis Fisch. Ex DC. (Zhi Gan Cao) root and the dried aqueous extract by LC-DAD. Journal of Pharmaceutical and Biomedical Analysis. 2008; 47(3): 495-500. 250 Title of Project: Exploring evidence of safety of use of Chinese herbal medicine for women with breast cancer (FOR Code/s): 1104 Supervisor: A/Professor Chun Guang Li Contact: [email protected] Co-supervisor: Dr Xiaoshu Zhu Contact: [email protected] A/Prof Yun Xu [email protected] Location of Project: Campbelltown Project Background Many women with breast cancer or history of breast cancer use Chinese herbal medicine (CHM) for managing adverse effects or for future prevention [1], however there are concerns about whether CHM is safe alternative for women with breast cancer in terms of potential impact on the sex hormones, given the link between higher level of sex hormones and breast cancer is well established. This project is part of a series of study under a theme of complementary and alternative medicine (CAM) research in breast cancer; it is also an international collaborative project preparing for a clinical trial in the near future. Aim of Study: To evaluate the contents of phytoestrogens in defined Chinese herbal formula Methods: An extensive literature review will be conducted to evaluate possible phytoestrogen compounds in individual herbal ingredient of the formula. Contents of potential phytoestrogens in the formula extracts will be determined by HPLC or LC-MS. Estrogenic activity in cells may also be investigated. Ethics Application Requirements: N/A Key References: 1. Kremser, T., et al., Use of complementary therapies by Australian women with breast cancer. The Breast, 2008. 17: p. 387-391. 251 Title of Project: Factors affecting the diffusion of actives in complementary medicines through the dermis in topical products (FOR Code/s): 1104 Supervisor: A/Prof Chun Guang Li Contact: [email protected] Co-supervisor: Dr. Jim Rowe [email protected] Location of Project: Campbelltown Project Background Topical dosage forms may be intended for local action or for systemic therapy. When a preparation is applied to skin the clinical result arises from a sequence of processes: a) Release of the medicament from the vehicle. b) Penetration through the skin barriers. c) Activation of pharmacological response. Effective therapy optimizes these steps as they are affected by three components, the drug, the vehicle and the skin. Various methods have been used to measure the release and skin penetration of an active from a particular topical formulation. Perhaps the best “in vitro” method used is Franz Cell technology where the preparation is placed on a semi permeable membrane and the active diffuses through the membrane into a receptor compartment and the amount released in determined as a function of time. This project will involve comparing the skin penetration of several topical complementary products by calculating the flux. Aim of Study: To determine the effect of the addition of a skin penetration enhancer to topical products. Ethics Application Requirements: N/A Key References: 1. Pharmaceutics: The Science of Dosage Form Design. Ed Aulton ME. 2nd Ed.; 499- 533. 2. www.permeagear.com. 3. Internet references on Franz cells 252 Title of Project: Tropical rainforest plants as a source of anti-inflammatory compounds for the treatment of Alzheimer’s disease (FOR Code/s): 1104 Supervisor: Prof. Gerald Muench Contact: [email protected] Co-supervisor: Dr. Frank van der Kooy Contact: : [email protected] Dr. Erika Gyengesi [email protected] Location of Project: Campbelltown Project Background In Alzheimer’s disease, one of the major causes of neuronal degeneration is chronic inflammation of the brain. Chronic inflammation causes the production of oxygen free radicals (“oxidative stress”), which damage lipids, proteins and DNA, and thus cause cell death. Terrestrial plants have evolved sophisticated antioxidant defences against oxidative stress including radicals produced by exposure to UV light. One strategy they use is the production of small anti-oxidant compounds such as polyphenols that have been shown to possess antioxidant, anti-inflammatory and neuroprotective properties. Having evolved in tropical latitudes, where exposure to high UV intensities are part of the normal environment, tropical rainforest plants are expected to have also developed efficient defences against the potential damage of long-term solar irradiation and photo-oxidative stress. The identification of such compounds in collaboration with a leading biotechnology company in North Queensland in a variety of high throughput assays will be the major part of this honours project. Aim of Study: 1) To determine the potency of a variety of extracts from tropical rainforest plants to down-regulate the LPS, IFN-γ induced production of free radicals (superoxide and nitric oxide) and pro-inflammatory cytokines (IL-6 and TNF) in immortalized murine microglia (anti-inflammatory potential). 2) To fractionate potent extracts and ultimately isolate the active compound, and determine its / their chemical structure (s) using modern analytical and spectrometric methods Methods: Cell culture, ELISA, Natural products extraction, Chromatography, Gas chromatography / Mass spectrometry (GC or HPLC/MS), NMR Ethics Application Requirements: N/A Key References: Gunawardena D, Shanmugam K, Low M, Bennett L, Govindaraghavan S, Head R, Ooi L, Münch G. Determination of anti-inflammatory activities of standardised preparations of plant- and mushroom-based foods. Eur J Nutr. 2013 53(1):335-43 Steele ML, Truong J, Govindaraghavan S, Ooi L, Sucher NJ, Münch G. Cytoprotective properties of traditional Chinese medicinal herbal extracts in hydrogen peroxide challenged human U373 astroglia cells. Neurochem Int. 2013 Apr;62(5):522-9. doi: 10.1016/j.neuint.2012.08.018. Epub 2012 Sep 11. 253 Title of Project: Acupuncture to treat sleep disorders during pregnancy development of a treatment protocol (FOR Code/s): 1104 Supervisor: Caroline Smith Contact: [email protected] Co-supervisor: Hannah Dahlen Contact: [email protected] Location of Project: Campbelltown campus Project Background Sleep is governed by circadian and endocrine systems, and reduced sleep may contribute to metabolic dysfunction. Many pregnant women experience frequent night waking, insomnia, and restless sleep during their pregnancy. These sleep disturbance changes are modified by the pregnancy and by trimester specific changes (O'Keeffe M and St-Onge MP 2012). However, there is little understanding of women’s experience of sleep disorders during pregnancy. The treatment of poor quality sleep during pregnancy is impacted by medication contra-indicated during pregnancy. Consequently there is interest in non pharmacological treatments to improve sleep quality and insomnia during pregnancy. A Cochrane systematic review of acupuncture to treat insomnia found some encouraging evidence of acupuncture with improving sleep quality however the methodological quality of trials was poor (Cheuk DKL, Yeung WF et al. 2012). A review of acupuncture administered during pregnancy also found positive results although the trials were small (Hollenbach D, Broker R et al. 2013). A review of non -pharmacological interventions for improving sleep quality found exercise, acupuncture and massage improved sleep, however study quality was poor. Future studies are needed to understand women’s sleep patterns in pregnancy, and their views about participating in clinical studies. Aim of Study: To examine women’s sleep during pregnancy, and for a group of women with difficult sleep to examine their interest in using complementary therapies. Methods: A cohort of pregnant women will be recruited from the community, via advertising, pregnancy groups or through advertising, and their pattern of sleep will be tracked over two trimesters of pregnancy. Women will be required to keep a sleep diary, and to complete a sleep questionnaire. For women with difficult sleep they will be invited to participate in a focus group where their interest and views with participating a clinical trial of a complementary therapy such as acupuncture or massage will be explored. Ethics Application Requirements: Ethics approval will be sought Key References: Cheuk DKL, Yeung WF, Chung KF and W. V. (2012). "Acupuncture for insomnia." Cochrane Database of Systematic Reviews Issue 9. Art. No.: CD005472. Hollenbach D, Broker R, herlehy S and Stuber K (2013). "Non-pharmacological interventions for sleep quality and insmnia during pregnancy: a systematic review." J Can Chiropr Assoc 57(3): 260-270. O'Keeffe M and St-Onge MP (2012). "Sleep duration and disorders in pregnancy: implications for glucose metabolism and pregnancy outcomes." International Journal of Obesity: 1-6. 254 Title of Project: The role of St John’s wort and exercise with the management of depression (FOR Code/s): 1104 Supervisor: Caroline Smith Contact: [email protected] Co-supervisor: John MacDonald Contact: [email protected] Co-supervisor: Bobby Cheema Contact:[email protected] Location of Project: Campbelltown campus Project Background Mental illness is one of the most important health issues facing young Australians. The prevalence of mental health disorders in 18-24 year olds is 26% (ABS 2007). Young men are least likely to access formal professional help for mental health conditions, and their reluctance to seek assistance can lead to further psychological distress. New strategies that are attractive, accessible and increase mental health support to young men are urgently needed. Australians are high users of complementary medicines (CM) (Xue, Zhang et al. 2007). High quality evidence demonstrates St Johns Wort has been shown to be superior to placebo and equivalent with tricyclic antidepressants for mild to moderate depression (Linde, Ramirez et al. 1996). Research has identified CM and self-help strategies such as exercise are preferable by many people living with depression to pharmacological treatment for depression (Highet, Hickie et al. 2002). However, it is unclear whether young men with depression are interested to use these particular modalities. Aim of Study: To evaluate the acceptability of exercise and St John’s Wort to support the mental health needs of young men in our local community. Methods: We will administer a questionnaire and interview with men aged 18-25 years. Participants will be recruited from the community in the vicinity of University of Western Sydney campuses. Participant’s views towards management strategies for depression will be explored, this will involve qualitative and quantitative data collection and analysis. Ethics Application Requirements: Ethics approval will be sought. Key References: ABS (2007). "Mental health of young people, 2007." Australian Bureau of Statistics 4 8 4 0 . 0 . 5 5 . 0 0 1. Highet, N. J., I. B. Hickie and T. A. Davenport (2002). "Monitoring awareness of and attitudes to depression in Australia." Medical Journal of Australia 176(10): S63. Linde, K., G. Ramirez, C. D. Mulrow, A. Pauls, W. Weidenhammer and D. Melchart (1996). "St John's wort for depression—an overview and meta-analysis of randomised clinical trials." Bmj 313(7052): 253-258. Xue, C. C., A. L. Zhang, V. Lin, C. Da Costa and D. F. Story (2007). "Complementary and alternative medicine use in Australia: a national population-based survey." The Journal of Alternative and Complementary Medicine 13(6): 643650. 255 Title of Project: Use of complementary medicine and therapies for the treatment of vaginal thrush (FOR Code/s):1104 Supervisor: Caroline Smith Contact: [email protected] Co-supervisor: Suzanne Cochrane Contact: [email protected] Location of Project: Campbelltown campus Project Background Recurrent vaginal thrush affects 5-8% of women of reproductive age Symptoms can have a major impact on both women and their partners(Hong E, Dixit S et al. 2014). Conventional treatment can be expensive and provides little long term relief for women. In addition women may experience side effects from treatment. Due to the lack of effective treatment women frequently turn to the use of complementary and alternative medicines including treatments such as yoghourt, lactobacillus supplements and tea tree oil(Watson CJ, Pirotta M et al. 2012). A recent study indicated 64% of women have previous used a complementary medicine (Nyirjesy P, Robinson J et al. 2011). However, there is a lack of research describing the effectiveness and safety of these therapies. Further research regarding the use and effectiveness of these therapies is needed. Aim of Study: 1. To undertake a systematic review of the Complementary Medicine literature regarding its application to treat vaginal thrush. 2. To examine women’s interest to participate in a clinical study. Methods: The study will involve: 1) Review of the literature relating to complementary medicines and vaginal thrush. The literature will be systematically searched to identify key articles. This data will be extracted and the literature synthesised. 2) Women with a history of thrush will be recruited from the community to participate in a study to explore their experience of managing heart disease, and to their views about engaging in a trial of a complementary medicine. A questionnaire and interview will be undertaken with a small sample of women to explore areas of the survey in greater detail. Ethics Application Requirements: Ethics approval will be sought. Key References: 1. Hong E, Dixit S, Fidel PL, Bradford J and F. G (2014). "Vulvovaginal candidiasais as a chronic disease: diagnostic criteria and definition." Journal of Lower Genital Tract Disease 18(1): 31-38. 2. Nyirjesy P, Robinson J, Mathew L, Lev-Sagie A, Reyes I and C. JF (2011). "Alternative Therapies in Women With Chronic Vaginitis." Obstet Gynecol 117: 856-861. 3. Watson CJ, Pirotta M and M. P (2012). "Use of complementary and alternative medicine in recurrent vulvovaginal candidiasis-results of a practitioner survey." Complement Ther Med 20: 218-221. 256 Title of Project: Identification of the anti-HIV compounds in the well-known antimalarial Chinese herb, Artemisia annua (FOR Code/s): 1104 Supervisor: Dr. Frank van der Kooy Contact: [email protected] Co-supervisor: Dr Chun Guang Li Contact: : [email protected] Location of Project: Campbelltown Project Background HIV, along with malaria and tuberculosis are the three ‘big’ infectious diseases ravaging the developing world. While there is a battle to develop pharmaceuticals which may combat these diseases, the rapid adoption of drug resistance in these organisms is hindering efforts. Ethnopharmacology looks at how people have traditionally treated diseases, often with the use of plants, potentially providing clues to an alternate understanding for the treatment of the disease and for the novel treatment of problem conditions. For example, people in developing countries discovered that by using an age-old Chinese medicinal plant, Artemisia annua, they could cure malaria [1]. This antimalarial action has already resulted in the development of artemisinin derivatives from this plant, which are currently being used as the first line treatment for malaria. There have been reports in Africa that people infected with HIV have also benefitted from the use of this same plant, A. annua. This is of obvious benefit, due additionally to the problem that HIV poses in the region and the potential low cost and high accessibility of the plant. We have therefore tested A. annua against HIV and have shown that it does indeed have very strong activity and importantly the activity is not caused solely by artemisinin [2]. (This project forms part of a larger project where the bioactivity of A. annua is being studied [1, 4] and the possible role of synergism of A. annua against malaria will be further investigated [1, 5]) Aim of Study: Identify the compound(s) responsible for the anti-HIV activity of A. annua. Methods: Extracts of about 20 different A. annua samples will be tested against HIV [2]. These samples will also be subjected to NMR and LC-MS metabolomics analysis. The activity data and the chemical fingerprints will be subjected to metabolomic analysis in order to identify the active compound(s) [3] Ethics Application Requirements: Appropriate Biosafety approval will be sought Key References: 1. Van der Kooy, F., Sullivan, S.E., (2013). The complexity of medicinal plants: The traditional Artemisia annua formulation, current status and future perspectives. Journal of Ethnopharmacology. 150:1-13. 2. Lubbe, A., Seibert, I., Klimkait, T., & Van der Kooy, F. (2012). Ethnopharmacology in Overdrive: The remarkable anti-HIV activity of Artemisia annua. Journal of Ethnopharmacology. 141:854-859. 3. Van der Kooy, F., Maltese, F., Choi, Y.H., Kim, H. K., & Verpoorte, R. (2009). Quality control of herbal material and phytopharmaceuticals with MS and NMR based metabolic fingerprinting. Planta Medica. 75: 763-775. 4. Liu, N. Q., Prager-van der Smissen, W., Ozturk, B., Smid, M., Van der Kooy, F., Foekens, J. A., Martens, J. W. M., & Umar, A. (2011). Molecular Portrait of Breast Cancer Cell Lines and Response to Artemisinin. European journal of Cancer. 47:152. 5. Julia Mouton, J., Jansen, O., Frédérich, M., Van der Kooy., F. (2013). Is artemisinin the only antiplasmodial compound in the Artemisia annua tea infusion? An in vitro study. Planta Medica. 79: 468-470. 6. 257 Title of Project: Carnivorous plants. Do they have the answer to multi-drug resistant tuberculosis? (FOR Code/s): 1104 Supervisor: Dr. Frank van der Kooy Contact: [email protected] Co-supervisor: Dr Joanne Packer Contact: : [email protected] Location of Project: Campbelltown Project Background Tuberculosis (TB), along with malaria and HIV are the three ‘big’ infectious diseases ravaging the developing world. While there is a battle to develop pharmaceuticals which may combat these diseases, the rapid adoption of drug resistance in these organisms is hindering efforts. Once almost eradicated from Australia, TB is staging a resurgence due the uncontrolled use of antibiotics, which has resulted in the development of multidrug resistant strains of the pathogenic organism. Thus, the discovery of novel sources of anti TB compounds is essential to prevent the further spread of the disease. One such source of new TB compounds comes from a very interesting group of carnivorous plants called the sundews (Drosera species). The purpose of these antibiotics in the plant is still unknown but it has been postulated that the plant use these antibiotics to disinfect its prey [1]. Previous studies have postulated that this group of compounds interferes with the electron transport chain of TB and thereby effectively stopping it in its tracks [2]. Aim of Study: 1 Demonstrate the level and nature of antibacterial activity of Australian Drosera species against Mycobacterium smegmatis 2 Compare metabolomic profiles of treated M. smegmatis against commonly used anti-TB agents to determine mechanism of action Methods: Bacterial growth will be assessed when challenged with varying concentrations of the carnivorous plant extract to determine the minimal inhibitory concentration of the plant extract. An optimum concentration and timepoint will be selected to determine the differential metabolomic profile of the control versus treated organism [3]. Subsequent experiments will assess what additional factors (eg diet, time of harvest, growth conditions etc) contribute to the antibacterial activity of the plant. While Mycobacterium tuberculosis is the pathogenic strain in TB infection, the model organism, M. smegmatis will be used initially to its morphologic similarity, ease of handling and relative safety. Positive results can later be translated into problematic strains in subsequent experiments. Ethics Application Requirements: Appropriate Biosafety approval will be sought Key References: 7. Egan, P.A., & Van der Kooy, F. (2013). Phytochemistry of the Carnivorous Sundew Genus Drosera (Droseraceae) and its Ethnopharmacological Relevance. Chemistry and Biodiversity. 10: 1774-1790 8. Van der Kooy, F., Meyer, J.J.M. & Lall, N. (2006). Antimycobacterial activity and possible mode of action of newly isolated neodiospyrin and other naphthoquinones from Euclea natalensis. South African journal of Botany. 72: 349-352. 9. Van der Kooy, F., Maltese, F., Choi, Y.H., Kim, H. K., & Verpoorte, R. (2009). Quality control of herbal material and phytopharmaceuticals with MS and NMR based metabolic fingerprinting. Planta Medica. 75: 763-775. 258 Title of Project: Effect of preparation methods on the bioactivity of traditional medicines (FOR Code/s): 1104 Supervisor: Dr. Frank van der Kooy Contact: [email protected] Co-supervisor: Dr Joanne Packer Contact: : [email protected] Location of Project: Campbelltown Project Background Ethnopharmacology studies how people from various cultures have traditionally treated diseases, often with the use of plants. This may potentially provide clues to an alternate understanding of the treatment of disease and for the novel treatment of problem conditions. The method of preparation of the treatment may affect the bioactivity of the preparation which may or may not be retained in the modern sample preparation techniques [1, 2]. Metabolomic analysis involves the simultaneous identification and quantitation of all small molecules in a given sample. This is usually done with NMR and/or LC-MS analysis followed by data reduction techniques and multivariate data analysis. The main objective is to identify chemical differences between different samples. Using this technique it is possible to link the bioactivity of one sample with the compound responsible for the observed activity. [3] Aim of Study: Study the chemistry of a selection of medicinal plants and assess the influence that the preparation method can have on the final formulation and bioactivity. Methods: As small selection of plants, used in traditional medicine in Australia and China, will be tested in a range of bioassays including for antibacterial, anticancer and anti-HIV activity. A range of preparation and extraction techniques will be applied and compared. Metabolomic analysis will be conducted on each of these plants and the bioactive compounds responsible for the activity will be identified. Ethics Application Requirements: Appropriate Biosafety approval will be sought Key References: 10. Van der Kooy, F., Sullivan, S.E., (2013). The complexity of medicinal plants: The traditional Artemisia annua formulation, current status and future perspectives. Journal of Ethnopharmacology. 150:1-13. 11. Zhang, Q., Y. M. Ma, et al. 2013 "Differences in Pharmacokinetics and Anti-inflammatory Effects between Decoction and Maceration of Sanhuang Xiexin Tang in Rats and Mice." Planta Med. 12. Van der Kooy, F., Maltese, F., Choi, Y.H., Kim, H. K., & Verpoorte, R. (2009). Quality control of herbal material and phytopharmaceuticals with MS and NMR based metabolic fingerprinting. Planta Medica. 75: 763-775. 259 Title of Project: Chinese herbal medicine for local treatments related side effect in women with breast cancer: development of a clinical protocol (FOR Code/s): 1104 Supervisor: Dr Xiaoshu Zhu Contact: [email protected] Co-supervisor: Dr Sue Cochrane [email protected] Location of Project: Campbelltown Project Background Breast cancer is the second leading cause of cancer deaths in women today. With the advances in medical knowledge, the survival rates for breast cancer have been improving for the past forty years; however the side effects of many conventional therapies in treating breast cancer are still harmful and distressing which decrease quality of life in patients and increase use of health care resources. In the case of surgically induced lymphoedema, there is no cure requiring daily management by compression and physical therapy. Skin reaction, radiodermatitis occurs nearly all patients undergo radiotherapy which may delay or interrupt the treatment and can produce spontaneous bleeding, ulceration and necrosis. Many cancer patients or survivors use Chinese herbal medicine (CHM) for managing adverse effects from conventional therapies including lymphoedema and radiodematitis. This project is part of a series of research study in the field. There has been a Honours project exploring any evidence of effectiveness on use of CHM on these two conditions through a systematic literature review with meta-analysis, findings and results will become available soon. Some preliminary findings indicate a need of a clinical protocol development. It is anticipated findings of this project will inform design of a clinical trial in the nature as part of PhD study. Aim of Study: Design a clinical protocol on use of CHM for lymthodema and radiodermatitis caused by local therapies in women with breast cancer Methods Literature review, in-depth review on a small cohort of CHM oncologists in China and CHM practitioners in Australia, working on patients with these conditions. Ethics Application Requirements: N/A Key References: Kremser, T., et al., Use of complementary therapies by Australian women with breast cancer. The Breast, 2008. 17(4): p. 387-394. 260 Title of Project: Outcome Measurement on TCM Pattern Diagnosis in Patients with Cancer (FOR Code/s): 1104 Supervisor: Dr Xiaoshu Zhu Contact: [email protected] Co-supervisor: Prof Pingping Li (Beijing Cancer Hospital China) Contact: [email protected] Location of Project: Campbelltown Project Background Many cancer patients or survivors use Chinese medicine (including herbal medicine and acupuncture) for managing adverse effects from conventional therapies [1, 2], however it is challenge to integrate biomedical evidence based methods into the framework of Chinese medicine, in particular its unique diagnostics, that is pattern differentiation. Aim of Study: To implement appropriately designed outcome measurements for TCM treatments that are reliable and valid. Methods: Mixed research methods will be employed for a design of outcome measurements in this project. Ethics Application Requirements: N/A Key References: 1. Kremser, T., et al., Use of complementary therapies by Australian women with breast cancer. The Breast, 2008(17): p. 387-391. 2. Price, S., G. Lewith, and K. Thomas, Acupuncture care for breast cancer patients during chemotherapy: a feasibility study Integrative Cancer Therapies, 2012. 5(4): p. 308-14. 261 Human Movement & Sports Science 262 Title of Project: Understanding the lives of global Health and Physical Education teachers in NSW schools (FOR Code/s): 1106, 1302 Supervisor: Bonnie Pang Contact: 98525413 Co-supervisor: TBA Contact: TBA Location of Project: Werrington South Project Background This project is concerned with the teaching experiences of HPE teachers with migrant backgrounds in NSW schools. Australia, along with the United States, Canada and New Zealand, has a strong and sustained history of immigration. One of the consequences of immigration is that Australia is characterized by a wide degree of cultural, linguistic, ethnic and religious diversity. Research shows that there is an increase in the global movements of teachers and that the Australian teaching workforce is becoming more diverse and bi/multilingual. The issue of this ‘super diversity' is central to Australian schooling. Aim of Study: This study aims to identify a range of factors including HPE teachers' classroom experience, assets, mobility, aspirations and cultural factors that influence their perceptions and experiences in teaching in Australia. This focus is critical to an understanding of HPE teachers' contemporary Australian migration experience and to Australia's HPE education in relation to Asian engagement in the Asian century. Methods: This study is underpinned by critical and socio-cultural perspectives. A combination of participatory visual methods, observations and interviews will be employed. Ethics Application Requirements: Ethics clearance will be sought from the UWS Human Research Ethics. Key References: Reid, C., Collins, J., & Singh, M. (2014). Goodbye ‘Mr Chips’: The Global Mobility of Australian-Educated Teachers. In Global Teachers, Australian Perspectives (pp. 135-168). Springer Singapore. Vertovec, S. (2007). Super-diversity and its implications. Ethnic and racial studies, 30(6), 1024-1054. 263 Title of Project: The ‘Healthy Environments and Active Living for Young People” (HEAL-YP) Project (FOR Code/s): 1106, 1302 Supervisor: Dr. Bonnie Pang Contact: 98525413 Co-supervisor: TBA Contact: TBA Location of Project: Werrington South Project Background The importance of built environment and healthcare infrastructures to health and physical activity is well documented in research. However, the lack of understanding of the everyday lives from young people’s perspectives about their built environment is what current research and policy makers might have overlooked and taken for granted. Aim of Study: The purpose of this study is to explore the relationships between young people’s perceptions, the built environment, and socio-cultural factors that shape their (in)active health and physical activity in their living area in Greater Western Sydney. Methods: This study is underpinned by critical and socio-cultural perspectives. A combination of participatory visual methods, observations and interviews will be employed. Ethics Application Requirements: Ethics clearance will be sought from the UWS Human Research Ethics. Key References: Malone, K. (2013). "“The future lies in our hands”: children as researchers and environmental change agents in designing a child-friendly neighbourhood." Local Environment 18 (3):372-395. doi: 10.1080/13549839.2012.719020. Smith, K., and Kotsanas. C. (2014). "Honouring young children’s voices to enhance inclusive communities." Journal of Urbanism: International Research on Placemaking and Urban Sustainability 7 (2):187-211. doi: 10.1080/17549175.2013.820211. 264 Title of Project: Health and Physical Education and Physical Activity in the Lives of Ethnic Minority Girls in Western Sydney (FOR Code/s): 1106, 1302 Supervisor: Bonnie Pang Contact: 98525413 Co-supervisor: TBA Contact: TBA Location of Project: Werrington South Project Background Participation levels in physical activity and the health status of young people are pressing issues in many Western countries. However, socio-cultural and educational experiences of ethnic minority young people, as well as the effect of inequalities upon them, remain under-examined. Minority ethnic young people are identified as ‘bodies-atrisk‘ because they do not conform to the physical activity and health regimes of contemporary Western societies. Socio-cultural researchers have argued that the dominant understandings of an ideal body and the ‘bodies-at-risk’ discourse have possibly overlooked different or alternative meanings of health, physical activity and bodies that could be significant to girls from English as Additional Language/Dialect backgrounds (EAL/D) in Western Sydney. Aim of Study: This study aims to understand the perceptions and experiences in Health and Physical Education (HPE) and physical activity of girls with EAL/D backgrounds in Western Sydney schools. Methods: This study is underpinned by critical and socio-cultural perspectives. A combination of participatory visual methods, observations and interviews will be employed. Ethics Application Requirements: Ethics clearance will be sought from the UWS Human Research Ethics. Key References: Gard, M., & Wright, J. (2001). Managing uncertainty: obesity discourses and physical education in a risk society. Studies in philosophy and education, 20, 535-549. doi: 10.1023/A:1012238617836 Pang, B., Macdonald, D., & Hay, P. (2013). “Do I have a choice?” The influences of family values and investments on Chinese migrant young people’s lifestyles and physical activity participation. Sport Education and Society. doi: 10.1080/13573322.2013.833504 265 Title of Project: Exploring the strengths of PDHPE students in health and wellbeing (FOR Code/s): 1106, 1302 Supervisor: Bonnie Pang Contact: 98525413 Co-supervisor: TBA Contact: TBA Location of Project: Werrington South Project Background Pang and Macdonald (In press) indicated that to promote student inclusion and engagement and to move beyond a traditional deficit approach, such as remedial interventions, requires utilizing a strengths-based approach which recognizes an array of knowledge and capabilities that students bring to education. The concentration on asset building rather than deficit/risk reduction is further substantiated by the establishment of a strengths-based approach as one of the five key propositions of the new Australian Health and Physical Education Curriculum (ACARA, 2012). Aim of Study: The study aims to explore PDHPE students’ perceived strengths in relation to their educational experiences in health and wellbeing units. Results have implications for promoting a positive learning experience to many students who are the first family members to attend university, come from low socioeconomic families and have ethnically diverse backgrounds. Methods: A combination of qualitative and quantitative research methods. Ethics Application Requirements: Ethics will be sought from the UWS Human Research Ethics. Key References: Pang, B., & Macdonald, D. (In press). Recognizing young Chinese Australian’s perceived resources within and beyond schooling. Pedagogy, Culture and Society. Yosso, T. J. (2005). Whose culture has capital? A critical race theory discussion of community cultural wealth. Race, Ethnicity and Education, 8(1), 69-91. doi: 10.1080/1361332052000341006 266 Title of Project: Coordination of downhill walking with and without auditory cueing (FOR Code/s): 110314 (Orthopaedics); 110317 (Physiotherapy); 110321 (Ecl. Physiotherapy); 110601 (Biomechanics); 110603 (Motor Control) Supervisor: Associate Professor Jack Crosbie Contact: [email protected] Co-supervisor: Dr. Amitabh Gupta Contact: [email protected] Location of Project: School of Science and health, Campbelltown campus (24.3.115) Project Background The purpose of this study is to explore the relationships between segmental movements (in three dimensions) during walking down level slopes of different inclinations and the effect that feedback has on the technique of walking. The literature on downhill walking is very sparse, particularly in comparison to level walking (or even walking up an incline). However the task of walking downhill is often a challenge, particularly for elderly individuals and younger people with knee pain. Furthermore, the challenge of walking on either a flat or downhill surface is often made more difficult due to a shift in attention such as having to focus on a different task at the same time or in fact perform two tasks synchronously (eg. “walk and talk”). A strategy which has been used to evaluate the dual-task paradigm has been to provide an audible cue during the performance of a motor task to determine changes in movement strategies. This type of augmented feedback requires a shift in focused attention from performing a motor task only, thereby challenging the neuromuscular system to have to adapt and maintain adequate control. There are no reports of any studies considering the changes in coordination and muscle activity in the lower limb during decline walking with a concurrent shift in attentional strategy, however, these represent functional demands commonly encountered and are often reported as problems by people with intrinsic changes due to age or impairment. Aim of Study: The aim of this study is to evaluate the effect of downhill walking on the gait pattern and the effect of audible cueing on the gait pattern. Methods: In this study, a population of healthy young and older participants will be recruited. A target number of 15 people under the age of 35 and 15 over the age of 60 will be tested. Participants will be required to perform a series of short walks at a comfortable speed on a treadmill, both on the flat and at two downward inclines, with and without an audio cue (metronome). Hip, knee and ankle joint kinematics and corresponding muscle activation levels of 6 lower limb muscles will be recorded on one leg using 3D motion capture (Optotrak) electromyography recording (Zerowire) instruments respectively. Dependant variables including joint excursions and muscle activation (amplitude and latency characteristics) will be determined and analysed statistically using standard repeated ANOVA procedures. Ethics Application Requirements: Ethical approval for this study has been granted (HREC Approval Number: H10299). Key References: Baker K, Rochester L, Nieuboer A. The immediate effect of attentional, auditory, and a combined cue strategy on gait during single and dual tasks in Parkinson's disease. Archives of Physical Medicine and Rehabilitation. 2007;88:1593600. Dorfman M, Herman T, Brozgol M, Shema S, Weiss A, Hausdorff JM, et al. Dual-Task Training on a Treadmill to Improve Gait and Cognitive Function in Elderly Idiopathic Fallers. Journal of Neurologic Physical Therapy. 2014. 267 Title of Project: ACTIVE RECOVERY - FITNESS & SPORTS PROGRAM FOR YOUTH WITH SERIOUS MENTAL ILLNESS IN WESTERN SYDNEY (FOR Code/s): 110699, 111714 Supervisor: A/ Prof Merom D. Contact: [email protected] Co-supervisors: Andrew Bennie Contact: [email protected] Location of Project: UWS Penrith and Campbelltown campuses Project Background People who have serious mental illness, including major depression, schizophrenia, and bipolar disorder, experience significant psychological, social, and cognitive disability and poor physical health due to the side effects of anti-psychotic drugs, which associate with large weight gain, metabolic disorder and risk of diabetes. Physical activity can improve these conditions, but the negative symptoms of their illness (e.g. low motivation, low self-esteem) highlight the challenge of maintaining an active lifestyle without a strong motivator. A review of the benefits of sport participation in adolescents underscore the psychological benefits of team sport, including reduced social isolation later in life, improved self-esteem, life satisfaction, reduced depression and anxiety symptoms and hopelessness and suicidality. These benefits were attributed to positive experiences from skills development, peer support and reduced body dissatisfaction. Aim of Study: 1) to evaluate the mental health benefits of fitness & sports program delivered to youth with serious mental health illness 2) to assess its impact on daily physical activity of youth with serious mental illness 3) to evaluate the effect of the program on social closeness and skills 4) to conduct qualitative evaluation of program implementation and satisfaction to be submitted to the organisations involved. Methods: This is a pilot study (pre/post evaluation design) with an aim to support a bigger NHMRC partnership grant. As a pilot it is a perfect topic for Honours research project. The program will be delivered to 10 young males and females with mental illness. Participants will be provided with active wear and accessories and transport to the venue by RichmondPRA, one of Australia’s most experienced non-profit mental health organisation. The project will engage youth with a serious mental illness in physical activities with emphasis on enjoyment, social interaction, fitness and continuity. The program will be delivered three times a week for 1.5 hours each session over 16 weeks. People with mental illness start at a very low level of fitness and may withdraw due to unpleasent sensation with increased efforts. The Active Recovery program will therefore be gradual. The idea is to devote up to 2 days to bootcamp activities with fitness assessments conducted for each participant pre, during & post program. The third day of the week will be devoted to sports such as mixed oztag, handball, basketball, soccer and volleyball. Each session will start with drills to improve game-specific skills in pairs or triplets. In the next hour the game is played and referees are rotates from the group. During the activity participants will wear motion sensors to provide immediate feedback on the duration at each intensity level and number of steps taken. The outcomes of this program will include clinically relevant measures of mental health, increases in daily physical activity, social interaction as well as barriers for program implementations and participants’ satisfaction and feedback. Participants will be transported to UWS sports ground. The project has funding to pay for the instructor time. This topic can involve two honours students given the quantitative and qualitative scope of this pilot and the social aspect. Data collection, analysis will be conducted by the research students with guidance from supervisor. Successful students will be able to start a lifelong career in the area of mental illness and sports participation working with governmental and non-governmental agencies. Ethics Application Requirements: yes, need to be submitted before the end of the year so approval is ready in January. Key References: 1. Eime RM et al A systematic review of the psychological and social benefits of participation in sport for children and adolescents: informing development of a conceptual model of health through sport. International Journal of Behavioral Nutrition and Physical Activity 2013, 10:98http://www.ijbnpa.org/content/10/1/98 2. Biddle S & Asare. Physical activity and mental health in children and adolescents: review of reviews.vBr J Sports Med 2011;45:886–895. doi:10.1136/886 bjsports-2011-090185 3. Masi, C. M., Chen, H., Hawkley, L. C., & Cacioppo, J. T. (2011). A meta-analysisof interventions to reduce loneliness. Personality and Social Psychology Review,15(3), 219–266 268 Title of Project: Muscle passive heating during half-time in soccer: testing a new garment (FOR Code/s): 110602 Supervisor: Ric Lovell Contact: [email protected] Co-supervisor: Paul Marshall Contact: [email protected] Location of Project: Campbelltown Project Background Research has challenged the typically passive half-time (HT) interval in soccer (Mohr at al., 2004; Lovell et al., 2013; Weston et al., 2011). During this period muscle temperature has been shown to decrease by 1.5-2.0 °C (Lovell et al., 2013; Mohr et al., 2004) which may result in impaired muscular performance at the start of the second-half. In support of this hypothesis, research studies administering active re-warm-ups in the latter 5-7 min of the HT interval have attenuated the decline in muscle temperature, and the associated decline in high-intensity tasks such as sprinting, jumping and dynamic strength (Mohr et al., 2004; Lovell et al., 2013). Interestingly, in a recent survey of elite soccer sports scientists and fitness coaches’ (Towlson et al, 2013), many considered that a HT re-warm-up was a valuable practice, but difficult to administer given the time and facility constraints. Hence work is required to identify alternative strategies to optimize player’s readiness to perform in the 2nd half of soccer matches. Aim of Study: To examine the effect of passive muscle heating during a soccer half-time interval upon muscle temperature, motor unit recruitment, maximal strength, rate of force development and sprint performance. Methods: Players will perform a 90-minute laboratory running simulation to mimic the demands of soccer match-play (SAFT90). At 15-minute intervals players’ maximum force and rate of force development will be assessed on an isokinetic dynamometer. Players sprint performance will be assessed throughout the protocol. At half-time, players will rest passively akin to a typical half-time interval, but in one trial will wear the passive heating garment. Ethics Application Requirements: This research program already has UWS Human Ethics (H10718) & UWS BSRC approval (B10717). Key References: 1. Towlson, C., Midgley, A.W., and LOVELL, R (2013). Warm-up strategies of professional soccer players: practitioners' perspectives. Journal of Sports Sciences, 31(13), 1393-1401. 2. LOVELL, R., Midgley, A., Barrett, S., Carter, D., Small, K. (2013). Effects of different half-time strategies on second half soccer-specific speed, power and dynamic strength. Scandinavian Journal of Medicine and Science in Sport, 23(1), 105-113. 3. Weston, M., Batterham, A., Castagna, C., Portas, M., Harley, J., Barnes, C. and LOVELL, R. (2011). Reduction in physical match performance at the start of the second half in elite soccer. International Journal of Sports Physiology and Performance, 6 (2), 174-82. 4. Mohr M, Krustrup P, Nybo L, et al. Muscle temperature and sprint performance during soccer matches – beneficial effect of re-warm-up at half-time. Scand J Med Sci Sports 2004; 14: 156-162. 269 Title of Project: Perceptions of older adults’ on participation in a social dancing program: determining the active and inactive ingredients of the program (FOR Code/s): 110699, 111714 Supervisor: A/ Prof Merom D. Contact: [email protected] Co-supervisors: Dr. Freya Macmillan Contact: [email protected] Location of Project: UWS Penrith and Campbelltown campuses Project Background As Australia confronts an unprecedented aging of the population, identifying effective strategies that address processes of aging and their adverse health outcomes have emerged as a major public health and economic challenge. Age-related physiological and cognitive declines are associated with declines in participation in physical activity. Dance is a complex sensorimotor rhythmic activity with additional mental and social components. The Dance Ageing Cognition and Economic (DAnCE) randomized controlled trial is an NHMRC funded research project aimed at testing the effect of a social dancing program on older adults’ falls and risk factors of falls. The trial was implemented within 23 retirement villages across the Greater Sydney area, and villages were randomized to an intervention or wait list control arm. The follow-up data finished in September, 2014, while control villages are still getting the dance program and will gradually finish their involvement in the trial until July 2015. This study is designed to gauge perceptions of older adults’ participation in two different dance-based programs: folk dance and ballroom dancing with a bigger trial that will test the efficacy of these programs on falls events, risk factors for falls and cost-effectiveness. Data from this project will inform health practitioners whether there is a potential to increase the proportion of inactive older adults who will take part in social dance as a lifelong solution to be active and if not why? The qualitative evaluation will identify issues related to program acceptability, difficulties, and maintenance. We will be able also to determine if social dancing is considered a fun activity that is suitably physically challenging and whether perceptions are different for novice versus experienced dance participants. Aim of Study: 1 )To learn how to conduct focus groups for the qualitative evaluation of health promotion programs 2)To engage and master the process of analyzing qualitative data 3)To gain experience in writing a qualitative paper Methods Participants in the intervention arm were invited to take part in focus groups discussion in their village. Dr. MacMillan, an expert in the area of qualitative evaluation of health promotion programs, and A/Pro Merom, the chief investigator of the project, have developed the semi-structured topic aid for the qualitative evaluation. The student is expected to review the literature on qualitative evaluation of dance based intervention, to conduct a few focus groups and to lead discussion, if confident, with the guidance of Dr MacMillan. In addition, the student will be expected to transcribe the recordings and to engage in analyzing the material under Dr. MacMillan’s guidance, to summarise he results and to contribute to paper writing. Ethics Application Requirements: No need to be submitted before the end of the year so approval is ready in January. Key References: 4. Merom et al Can social dancing prevent falls in older adults? A protocol of the Dance, Aging, Cognition, Economics (DAnCE) fall prevention randomised controlled trial 270 Title of Project: Playing Soccer in the Heat: do FIFA “cooling periods” work? (FOR Code/s): 110602 Supervisor: Ric Lovell Contact: [email protected] Co-supervisor: Jason Siegler Contact: [email protected] Location of Project: NSWIS, Sydney Olympic Park Project Background: Prior to the FIFA 2014 World Cup in Brazil, the governing bodies executive committee approved the use of “cooling periods” to alleviate the heat strain on players when matches are played in high environmental temperatures. Strategies to reduce the heat-induced stress on players are particularly welcome given the global expansion of the game, and the awarding of the 2022 World Cup to Qatar, where temperatures can often exceed 40 degrees Celsius. The purpose of the FIFA “cooling periods” is to reduce the risk of players incurring heat-related illnesses (such as heat exhaustion, heatstroke, heat cramps) by enabling them to ingest fluids to alleviate dehydration and heat-strain. The breaks are a couple of minutes in duration and are applied by officials (approximately 30 minutes into each half) if the match is played in conditions deemed hazardous to the player. However, there is no currently available evidence examining the utility of these cooling breaks upon measures of heat strain (body temperature) and hydration, and research is required to determine their effectiveness, together with other potential cooling strategies such as iceslurry ingestion (Stevens et al., 2013) and cold-wet towel application (Minett et al., 2012). Aim of Study: To examine the application of FIFA cooling periods on measures of heat strain, hydration status and physical performance of soccer players during simulated matches in hot environmental conditions. Methods: Amateur soccer players will perform a simulated match in an environmental chamber on three separate occasions. In a randomized fashion, trials will either exclude a cooling period (control), or administer 3-minute rest intervals during which the players will undertake fluid and cooling strategies. Heart rate, core body temperature, skin temperature, blood plasma volume and ratings of perceived exertion and thermal strain will be measured routinely. Ethics Application Requirements: This research proposal would be subject to approval from the NSWIS ethical committee. Key References: Minett, G.M., Duffield, R., Kellett. A., Portus, M. (2012). Effects of mixed-method cooling on recovery of medium-fast bowling performance in hot conditions on consecutive days. Journal of Sports Sciences, 30 (13), 1387-1396. Stevens, C. J., Dascombe, B., Boyko, A., Sculley, D., & Callister, R. (2013). Ice slurry ingestion during cycling improves Olympic distance triathlon performance in the heat. Journal of Sports Sciences, 31(12), 1271–1279. Agel, J., Evans, T.A., Dick, R., Putukian, M., Marshall, S.W. (2007). Descriptive Epidemiology of Collegiate Men's Soccer Injuries: National Collegiate Athletic Association Injury Surveillance System, 1988–1989 Through 2002–2003. Journal of Athletic Training, 42(2), 270-277. 271 Title of Project: Home and neighbourhood environment influences on young children’s physical activity levels (FOR Code/s): 110699 Supervisor: Ms Jill Hnatiuk Contact: TBD Co-supervisor: Dr. Thomas Astell-Burt Contact: [email protected] Location of Project: Penrith/Campbelltown campus Project Background The home and neighbourhood environment has been identified as an important influence on adult and youth health behaviours, including their physical activity participation.1,2 However, very little is known about how these environments impact young children’s (0-5 years) physical activity levels over time. Given the early childhood period is a time when physical activity behaviours begin to emerge, understanding the role the home and neighbourhood environment is critical for effectively shaping these health behaviours within the population. Aim of Study: The aim of this study is to examine home and neighbourhood environment predictors of young children’s physical activity Methods: This study will use data collected from the infant wave of the Longitudinal Study of Australian Children (LSAC), a cohort study of over 5000 families residing in Australia. Parental perceptions of the neighbourhood environment were collected at baseline via a self-report survey and children’s physical activity was assessed at age 2-3 and 4-5 years using a time use diary. Associations between parent-reported characteristics of the neighbourhood environment and children’s physical activity will be examined using regression models. Through this project, the Honours student will gain valuable skills in reviewing and critiquing literature, analysis of data, and interpreting and writing up the findings. It is anticipated that this work will lead to the publication of a scientific paper in a peer-reviewed journal. Ethics Application Requirements: Permission to use existing de-identified dataset. Key References: 1 Kaushal N, Rhodes RE. The home physical environment and its relationship with physical activity and sedentary behavior: A systematic review. Prev. Med. 2014; 67(0):221-37. 2 Duncan M, Spence J, Mummery WK. Perceived environment and physical activity: a meta-analysis of selected environmental characteristics. International Journal of Behavioral Nutrition and Physical Activity. 2005; 2(1):11. 272 Title of Project: Changes in young children’s physical activity and screen time in early childhood- does socioeconomic position play a role? (FOR Code/s): 110699 Supervisor: Ms Jill Hnatiuk Contact: TBD Co-supervisor: Professor Gregory Kolt Contact: [email protected] Location of Project: Penrith/Campbelltown campus Project Background Engaging in sufficient physical activity and limiting screen time is recommended for optimal health in early childhood.1,2 Despite this, many children are not engaging in recommended levels of these behaviours.3 It is not yet well-established, however, how these health behaviours change over the early childhood period and how they may differ by socio-economic position. This information will be useful for the development and the timing of intervention strategies in this age group. Aim of Study: The primary aim of this project is to examine change in young children’s physical activity and screen time over the early childhood period. A secondary aim is to determine how these changes may be modified by the socio-economic position of families. Methods: This study will use data collected from the Longitudinal Study of Australian Children (LSAC), a cohort study of over 5000 families residing in Australia. Children’s physical activity, screen time and socio-economic position was assessed via a time-use diary at age 2-3 and 4-5 and 6-7 years old. Stability of these behaviours will be examined using regression models. Through this project, the Honours student will gain valuable skills in reviewing and critiquing literature, analysis of data, and interpreting and writing up the findings. It is anticipated that this work will lead to the publication of a scientific paper in a peer-reviewed journal. Ethics Application Requirements: Permission to use existing de-identified dataset. Key References: 1 Timmons BW, LeBlanc AG, Carson V, et al. Systematic review of physical activity and health in the early years (aged 04 years). Appl. Physiol. Nutr. Metab. 2012; 37:773-92. 2 LeBlanc AG, Spence JC, Carson V, et al. Systematic review of sedentary behaviour and health indicators in the early years (aged 0-4 years). Appl. Physiol. Nutr. Metab. 2012; 37:753- 72. 3 Hnatiuk J, Salmon J, Hinkley T, Okely A, Trost SG. A review of preschool children's physical activity and sedentary time using objective measures. Am. J. Prev. Med. 2014. doi: 10.1016/j.amepre.2014.05.042 273 Title of Project: Socio-economic variation in family physical activity participation (FOR Code/s): 110699 Supervisor: Ms Jill Hnatiuk Contact: TBD Co-supervisor: Professor Gregory Kolt Contact: [email protected] Location of Project: Penrith/Campbelltown campus Project Background Regular participation in physical activity is important for health across the lifespan. Despite this, many parents of young children and young children themselves, are not meeting current physical activity recommendations1. As families spend the most time being physically active together during early childhood2, engaging in family-based physical activity together may be a strategy to increase physical activity levels in both children and their parents. No studies conducted to date, however, have identified longitudinal associations between family physical activity participation and parent and children’s physical activity and how this varies across socio-economic groups. Aim of Study: To identify changes in family physical activity participation over the early childhood period and determine longitudinal associations with parents' and children's physical activity levels Methods: This study will use data collected from the Longitudinal Study of Australian Children (LSAC), a cohort study of over 5000 families residing in Australia. Family physical activity participation, socio-economic position and parental physical activity level were assessed via parent-report questionnaire at multiple time points throughout early childhood. Children’s physical activity was assessed over the same time period via a time-use diary. Associations between family physical activity participation and children’s and parents’ physical activity will be examined using regression models. Through this project, the Honours student will gain valuable skills in reviewing and critiquing literature, analysis of data, and interpreting and writing up the findings. It is anticipated that this work will lead to the publication of a scientific paper in a peer-reviewed journal. Ethics Application Requirements: Permission to use existing de-identified dataset. Key References: 1 Australian Bureau of Statistics. Australian Health Survey: Physical Activity. 2011-2012. http://www.abs.gov.au/ausstats/[email protected]/Lookup/462FBA87B642FCA4CA257BAC0015F3CE?opendocument. 2 Alderman BL, Benham-Deal TB, Jenkins JM. Change in parental influence on children's physical activity over time. J Phys Act Health. 2010; 7:60-7. 274 Title of Project: The influence of pH on skeletal muscle adaptation to high intensity exercise training (FOR Code/s): 1106 Supervisor: Dr Jason Siegler Contact: 4620 3381 Co-supervisor: Dr Paul Marshall Contact: 4620 3915 Location of Project: Sport and Exercise Science Laboratories, Building 20, Campbelltown Campus Project Background The practice of inducing metabolic alkalosis, or elevating blood pH, to improve exercise tolerance has been prevalent within the field of sport science for approximately three decades (Carr, 2011; McNaughton, 2008). Throughout this period, applied research in this domain has investigated the ergogenic potential of various buffering agents (e.g. sodium phosphate, sodium bicarbonate or sodium citrate) spanning a wide range of performance outcomes and exercise tasks. Sodium bicarbonate (NaHCO3), arguably the most efficacious agent, is believed to mitigate fatigue through the attenuation of intramuscular acidity (Peart, 2012), although the physiologic mechanisms directly responsible for performance augmentation in humans are unknown. Indeed, many of the studies investigating the ergogenic potential of NaHCO3 focus on performance outcomes (e.g. time to task failure, cumulative work accomplished, time trial performance, etc.) (Carr, 2011; McNaughton, 2008) and only speculate about underlying mechanisms responsible for any benefit. In a recent study conducted in the Sport and Exercise Science Laboratories (SES) at UWS (supported by 2012 Seed Grant), we explored the acute neuromuscular response to fatigue under conditions of alkalosis. For the first time, we demonstrated a differential effect of alkalosis on maximum force versus maximum rate of force development (RFD) and the underlying muscle recruitment during a whole-body fatiguing task (Siegler, 2013). This differential effect of alkalosis on RFD versus maximum force, and the timing of this effect, implicates mechanisms involved in rapid activation of muscle and it’s shortening during maximum voluntary effort. Furthermore, these findings demonstrate independent effects of intracellular pH on cell membrane processes and the contractile proteins, all of which are expected to reduce the maximum RFD but not necessarily the maximum force. However, it is difficult to establish the extent to which the present acute response of alkalosis on maximum RFD can contribute to the skeletal muscle adaptation process that occurs after a period of training. Aim of Study: The primary aim of this study is to examine the strength and neuromuscular adaptations in skeletal muscle after a 12week period of high intensity training under alkalotic (e.g. elevated pH) conditions. Methods: Fifteen participants will be recruited to complete the 12-week training study. All testing and training will be conducted in the Sport Science Laboratories at the University of Western Sydney in Campbelltown. A randomised, double-blind control design will be implemented where participants will undergo a series of baseline strength and neuromuscular measurements, then proceed with the 12-week training protocol consisting of two days per week training one leg in an alkalotic condition (induced through sodium bicarbonate ingestion) and another two days per week training the contralateral leg under control (e.g. placebo) conditions. Alkalosis will be induced through ingestion of 0.3g/kg body weight (BW) of NaHCO3 in gelatin capsules dispensed at -90, -60, and -30 minutes prior to commencement of the training session. This ingestion protocol has been adapted from previous research findings to minimise symptoms of gastrointestinal distress. The training protocol will consist of a series of knee extension exercises designed to improve strength and power. Upon conclusion of the 12-week protocol, strength and power will again be measured to determine any influence of the intervention. Measurements of strength and power will be conducted on an isokinetic dynamometer, where as neuromuscular measurements will be assessed through surface electromyography and muscle nerve stimulation. Ethics Application Requirements: Ethical approval currently being obtained Key References: Carr AJ, Hopkins WG, Gore CJ (2011) Effects of acute alkalosis and acidosis on performance. 41:801–814. McNaughton LR, Siegler J, Midgley A (2008) Ergogenic effects of sodium bicarbonate. Curr Sports Med Rep 7:230–236. Peart DJ, Siegler JC, Vince RV (2012) Practical recommendations for coaches and athletes: a meta-analysis of sodium bicarbonate use for athletic performance. J Strength Cond Res 26:1975–1983. Siegler JC, Marshall PWM, Raftry S, et al. (2013) The differential effect of metabolic alkalosis on maximum force and rate of force development during repeated, high-intensity cycling. J Appl Physiol 115:1634–1640. 275 Title of Project: Effects of siesta on blood pressure and muscle sympathetic nerve activity (FOR Code/s): 110602, 110901 Supervisor: Dr. Chloe Taylor Contact: [email protected] Co-supervisor: Prof. Vaughan Macefield Contact: v.macefield.uws.edu.au Location of Project: Campbelltown Project Background It is well established that the incidence of cardiovascular events (such as myocardial infarction) is highest in the morning hours after waking (Muller et al., 1989). It has also been reported that a secondary peak occurs in the afternoon, which has been attributed to daytime napping or ‘siesta’ in some populations. Whilst Bursztyn and Stessman (2005) reported an increased risk of mortality in those who partake in siestas, the cause is currently not clear. Previous studies indicate a link between the high prevalence of cardiovascular events in the morning and increases in blood pressure and sympathetic activity at this time. We therefore hypothesise that similar mechanisms maybe involved when waking from daytime sleep. Aim of Study: To determine the effects of awakening from daytime sleep on blood pressure and muscle sympathetic nerve activity. Methods: 12 participants will be recruited for the study. Each participant will be required to attend the laboratory on one afternoon. Participants will lie in a supine position in a quiet room while continuous measurements of blood pressure, heart rate, respiration and muscle sympathetic nerve activity (MSNA) will be recorded. Microneurography is an invasive technique for the direct measurement of MSNA. It involves the insertion of a fine needle electrode into the common peroneal nerve (in the leg, at the level of the fibular head). Participants will wear a blindfold and be asked to relax whilst remaining in a supine position. Lack of response (via handheld push button) to a short audio cue will be used to determine sleep. After a minimum of 20 mins sleep, the participant will be woken by an alarm and the blindfold will be removed. Physiological variables will be measured for a further 30 mins following waking. Additional experiments will be performed if sleep is not initiated. Ethics Application Requirements: Ethical approval has been granted (H9577) Key References: Bursztyn, M. & Stessman, J. (2005). The siesta and mortality: twelve years of prospective observations in 70-year-olds. Sleep, 28: 345-347. Muller, J. E., Tofler, G. H. & Stone, P. H. (1989). Circadian variation and triggers of onset of acute cardiovascular disease. Circulation, 79; 733-743. Muller, J. E., Tofler, G. H. & Verrier, R. L. (1995). Sympathetic activity as the cause of the morning increase in cardiac events. Circulation, 91: 2508-2509. 276 Title of Project: Predicting participation in the Healthy Environments and Active Living Study (HEALStudy) (FOR Code/s): 1106 (Human Movement and Sports Science); 1117 (Public Health and Health Services); Supervisor*: Dr Freya MacMillan Contact: [email protected] Supervisor*: Dr Thomas Astell-Burt Contact: [email protected] Location of Project: Campbelltown campus * Joint supervision – each contributing equally Project Background The Healthy Environments and Active Living Study (HEALStudy) is exploring how changes in built environment potentially influence community health in South West Sydney. Participants in the HEALStudy are being tracked over time, but some people will drop out over time due to various reasons (e.g. leaving the area). Meanwhile, other participants in the main survey may or may not choose to take part in sub-studies involving use of accelerometers. Continued participation and drop-out is, therefore, not random and this could have important implications for the results. Aim of Study: The aim of this study is to examine the factors which predict participation and drop-out in the HEALStudy and associated sub-studies. Methods: State-of-the-art techniques to resolve attrition and missing data in longitudinal studies will be reviewed in order to understand their cost-benefits. A selected set of those techniques will then be applied to data from the HEALStudy using relevant statistical models. Ethics Application Requirements: Ethical approval has already been granted for this study and data collection is underway. Key References: Tambs K, Ronning T, Prescott CA, Kendler KS, Reichborn-Kjennerud T, et al. (2009) The Norwegian Institute of Public Health twin study of mental health: examining recruitment and attrition bias. Twin Res Hum Genet 12: 158–168 STERNE, J. A., WHITE, I. R., CARLIN, J. B., SPRATT, M., ROYSTON, P., KENWARD, M. G., WOOD, A. M. & CARPENTER, J. R. 2009. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. Bmj, 338: b2393. 277 Title of Project: Idiopathic toe walking: Can a novel exercise program to address sensory and motor skill challenges be beneficial? (FOR Code/s): 11 Medical and Health Sciences, 111403 Paediatrics, 110603 Motor Control, 730299 Public Health Supervisor: Dr Stef Penkala Contact: Ph 4620 3742, email [email protected] Location of Project: Campbelltown Project Background Gait anomalies in early childhood are a concern for parents and common source of health professional referral. Toewalking defined as the absence of heel contact can be a normal gait variant until 3 years of age (1). However, aetiology including disease, neurological influences and trauma, require screening (1). In the absence of medical conditions, persistent toe walking beyond 3 years of age is considered idiopathic, effecting around 12 % of the paediatric population (2). While idiopathic toe walking (ITW) has no medical cause, links to speech, language (3) and sensory processing (4) difficulties associated with vestibular and sensory anomalies are reported. In a case control study (n= 60) children with ITW demonstrated hypersensitivity of vibration perception threshold (p<0.001), lower Standing Walking Balance subtests (p=0.47) and motor proficiency (p=0.001), compared to norms (4). A range of treatments have been advocated in the management of toe walking including, surgery, casting, stretching, botulinum toxin type A injections and orthotics, particularly in the presence of tight calf structures. However, toe walking can persist beyond the resolution of tight calf structures (5). Interventions beyond the ‘structural’ framework require consideration. Given the links between proficient sensory and motor control with physical activity participation, ITW interventions that can address sensory and motor skill challenges may be beneficial. This study will investigate a novel exercise program to address sensory and motor skill challenges in children with ITW. Aim of Study: The aim of the study of the study is to investigate the benefits of a novel exercise program to address sensory and motor skill challenges in children with ITW. Methods: This study will use a case-control design. Children with ITW will be recruited and screened with the Toe Walking Tool (6) for inclusion. Children will be asked to participate in 8 to 12 exercise sessions challenging sensory and motor input. Pre and post measures will include vibration perception threshold, Standing Walking Balance subtests and motor proficiency. Ethics Application Requirements: NEAF Required Key References: 1. Williams CM, Timey P and Rawicki B Have We Progressed in our Knowledge of the Causality and Treatment of this Gait Type? JAPMA 2014, 104:3 253-61 2. Fox A, Deakin S, Pettigrew G, Paton R: Serial casting in the treatment of idiopathic toe-walkers and review of the literature. Acta Orthop Belg 2006, 72:722-730. 3. Shulman LH, Sala DA, Chu MLY, McCaul PR, Sandler BJ. Developmental implications of idiopathic toe walking. J Pediatr. 1997, 130:541-546. 4. Williams CM, Tinley P, Curtin M, Wakefield S and Nielsen S. Is Idiopathic Toe Walking Really Idiopathic? The Motor Skills and Sensory Processing Abilities Associated With Idiopathic Toe Walking Gait. J Child Neurol 2014, 29: 71 5. Eastwood DM, Menelaus D, Dickens RV, Broughton NS, Cole WG. Idiopathic toe-walking: does treatment alter the natural history? J Pediatr Orthop B. 2000, 9:47-49. 6. Williams CM, Tinley P and Curtin M The Toe Walking Tool: A novel method for assessing idiopathic toe walking children. Gait & Posture 2010, 32: 508–511 278 Title of Project: Facilitators and Barriers for Indigenous Sport Coaches: An Ecological Perspective. (FOR Code/s): DIVISION 11 MEDICAL AND HEALTH SCIENCES >> GROUP 1106 HUMAN MOVEMENT AND SPORTS SCIENCE Supervisor: Andrew Bennie Contact: [email protected] Co-supervisor: TBC Contact: TBC Location of Project: 1. Penrith 2. Campbelltown (TBC) This project is suitable for 1-3 Honours students Project Background Sport plays an important role for many Australians. For example, within Indigenous communities, sport provides opportunities for social participation, social identity construction, and meaningful engagement in the workforce (Campbell & Sonn, 2009). Besides Campbell & Sonn’s examination of Indigenous Australian Football League (AFL) players’ perspectives on transitioning into the AFL, little is known about the nature of Indigenous athlete development and the issues and challenges associated with transition to post career employment. Even less is known about Indigenous sport coaches and whether coaching is a viable career pathway for Indigenous people. Further research is warranted to help develop a more detailed understanding of the facilitators and challenges for Indigenous people in the field of sport coaching. Aim of Study: The purpose of this project is to conduct an extensive investigation into the current state of Indigenous coaching within professional sport contexts in Australia. Specifically, we are focusing on generating strengths based knowledge about pathways into professional coaching roles for Indigenous people. Methods: Qualitative research methods will be used to capture detailed and personalised accounts about Indigenous sport coaching. A socio ecological framework will underpin this research. To ensure a holistic representation of Indigenous perspectives are captured, current coaches and former athletes will be interviewed using a semi-structured approach. Additionally, male and female participants from various team (e.g., basketball, netball, rugby league, rugby union, hockey) and individual sport (e.g., boxing, athletics) contexts will be invited to take part in this research. Ethics Application Requirements: An ethics application will be completed by the time the project commences. Key References: Bronfenbrenner, U. (1993). The ecology of cognitive development: research models and fugitive findings. In R.H. Wozniak & K.W. Fisher (Eds.), Development in context: Activity and thinking in specific environments (pp. 3– 24). Hillsdale, NJ: Erlbaum. Campbell, E. E. & Sonn, C. C. (2009). Tranisitioning into the AFL: Indigenous football players’ perspectives. Athletic Insight, 11(3). ISSN 1947-6299 Patton, M. Q. (2002). Qualitative research and evaluation methods (3rd ed.). Thousand Oaks: Sage Publications. Schinke, R. J., Michel, G., Gauthier, A. P., Pickard, P., Danielson, R., Peltier, D., et al. (2006). The adaptation to the mainstream in elite sport: A Canadian Aboriginal perspective. The Sport Psychologist, 20, 435-448. 279 Title of Project: Pathways to Parasport coaching: Athlete and Coach Development (FOR Code/s): DIVISION 11 MEDICAL AND HEALTH SCIENCES >> GROUP 1106 HUMAN MOVEMENT AND SPORTS SCIENCE Supervisor: Andrew Bennie Email: [email protected] Co-supervisor: TBC Email: TBC Location of the Project: Penrith; 2. Campbelltown (TBC) This project is suitable for 1-2 Honours students Background: Participation in Parasport competitions has grown significantly since the inception of competition in the early 1980s; however, limited research has focused on how coaches develop knowledge about coaching Parasport athletes. Indeed, previous research primarily focused on the roles, philosophies, and strategies for athlete development (Banack, Sabiston & Bloom, 2011; Tawse, Bloom, Sabiston & Reid, 2012). As such, there is potential to build a body of knowledge about pathways to high performance coaching and participation for Australian athletes and coaches within the Parasport sport movement. Aim of Study: This study has two aims: 1. Investigate career evolution and knowledge development for coaches of Parasport athletes. 2. Explore the pathway from youth sport to Paralympic and other high performance Parasport competition amongst athletes with a physical disability. Methods: Qualitative research methods will be used to capture detailed and personalised accounts about Parasport coach development. A socio ecological framework will underpin this research. To ensure a holistic representation of Parasport perspectives are captured, current male and female coaches from various team (e.g., wheelchair basketball, wheelchair rugby, wheelchair tennis) and individual sport (e.g., swimming, athletics, cycling) contexts will be interviewed using a semi-structured approach. Ethics Application Requirements: An ethics application will be completed by the time the project commences. Key References: Banack, H. R., Sabiston, C.M., & Bloom, G. A. (2011). Coach Autonomy Support, Basic Need Satisfaction, and Intrinsic Motivation of Paralympic Athletes. Research Quarterly for Exercise and Sport, 82(4), 722-730. Bronfenbrenner, U. (1993). The ecology of cognitive development: research models and fugitive findings. In R.H. Wozniak & K.W. Fisher (Eds.), Development in context: Activity and thinking in specific environments (pp. 3– 24). Hillsdale, NJ: Erlbaum. Patton, M. Q. (2002). Qualitative research and evaluation methods (3rd ed.). Thousand Oaks: Sage Publications. Tawse, H., Bloom, G. A., Sabiston, C. M., & Reid, G. (2012). The role of coaches of wheelchair rugby in the development of athletes with a spinal cord injury. Qualitative Research in Sport, Exercise and Health, 4(2), 206-225. 280 Title of Project: Factors Affecting the Developmental Pathways of Officials in Sport: A Qualitative Study of Professional Officials. (FOR Code/s): DIVISION 11 MEDICAL AND HEALTH SCIENCES >> GROUP 1106 HUMAN MOVEMENT AND SPORTS SCIENCE Supervisor: Andrew Bennie Contact: [email protected] Co-supervisor: TBC Contact: TBC Location of Project: 1. Penrith 2. Campbelltown (TBC) This project is suitable for 1-2 Honours students Project Background Officials such as umpires and referees are essential to the ongoing production of organised sporting events. There has been much research into why athletes participate in their chosen sports but very little research into why officials participate on a long term basis (Kellet & Shilbury, 2007). At present evidence suggests that many sports are experiencing difficulties in umpire/referee recruitment and retention (Arehart, 2002). In fact, statistics show that the number of officials in Australia has dropped by 26% since 1997 (ABS, 2001), with many officials dropping out in their first two years of officiating (Stevenson, 2001). As officials are an integral part of organised sport, the recruitment and retention of officials should be an area of focus for researchers. Aim of Study: The purpose of this study is to gain an in depth understanding of how professional officials develop their expertise over time. This study also aims to gain insight into the key factors that lead to the long term engagement of semi professional and professional referees and umpires in their chosen sports. Methods: This qualitative project will utilise individual or focus group interviews to collect data about experiences as sporting officials. Interviews enable a rich description and interpretation of the participants’ feelings, thoughts, emotions and beliefs about those experiences (Patton, 2002). Participants will be asked to explain how their development as a sport official has been shaped over time in relation to training patterns and the influence of significant others (e.g., parents, peers, coaches, siblings). Interview data will be analysed based on Patton’s (2002) thematic analysis procedures. Ethics Application Requirements: An ethics application will be completed by the time the project commences. Key References: Côté, J., Baker, J., & Abernathy, B. (2003). From play to practice: A developmental framework for the aquisition of expertise in team sport. In K. A. Ericsson, Expert performance in sport: Advances in research on sport expertise (pp. 89-114). Champagne, IL: Human Kinetics. Fraser-Thomas, J., & Côté, J. (2007). Understanding adolescents’ positive and negative developmental experiences in sport. The Sport Psychologist , 23, 3-23. Fraser-Thomas, J., Côté & Deakin, J. (2007). Understanding dropout and prolonged engagement in adolescent competetive sport. Psychology of Sport and Exercise (9), 645-662. Kellet. P, & Shilbury, D. (2007). Umpire participation: Is abuse really the issue? Sport Management Review (10), 209229. Patton, M. Q. (2002). Qualitative research and evaluation methods (3rd ed.). Thousand Oaks: Sage Publications. 281 Title of Project: Determination of physiological thresholds in Soccer (FOR Code/s): 110602 Supervisor: Jason Siegler Contact: [email protected] Co-supervisor: Ric Lovell Contact: [email protected] Location of Project: Campbelltown & Westfields Sports High School Project Background: Laboratory-based physiological testing in team-sports such as soccer is not commonly undertaken because of the significant time, expertise, and facility requirements. Even at the professional level, players will often perform field-based testing, which can be time and cost-efficient. Contemporary field-tests such as the Yo-Yo assessments are routinely performed because they are intermittent in nature and better reflect the energetic demands of soccer. However, these endurance-type tests often require other physical attributes such as lower limb power or strength to change direction, and also the ability to accelerate to high velocities. The composite nature of these tests makes it difficult to determine the precise physical strengths and weaknesses of players, and the results offer no information in regards to training prescription or the monitoring of player workloads. Identifying a players physiological thresholds (i.e. anaerobic threshold, maximal aerobic speed) facilitates individual training prescription (Dupont et al., 2004) and permits a comprehensive analysis of a their work-load in training and matches (Lovell & Abt, 2013; Hunter et al., 2014). However, work is required to identify the most appropriate tests and measures to determine physiological thresholds on the training field. Aim of Study: To determine the validity of field-based tests such as the multi-stage fitness test (MSFT) and the VAMEVAL to determine physiological thresholds Methods: 20 soccer players will perform 3 incremental tests to exhaustion (treadmill, MSFT, and VAM-EVAL) on different days in a randomized fashion. Players will wear a beat-to-beat HR monitor and a portable gas analysis system. The heart rate variability threshold (Buchheit et al., 2007) and ventilation threshold (Lovell & Abt, 2013) will be ascertained in accordance with previous literature. Ethics Application Requirements: This research program already has UWS Human Ethics (H9807) & UWS BSRC approval (B9815). Key References: 5. Hunter, F., Bray, J., Towlson, C., Smith, M., Barrett, S., Madden, J.L., Abt, G., and LOVELL, R (2014). Individualisation of Time-Motion Analysis: A Method Comparison and Case Report Series. International Journal of Sports Medicine. In Press. 6. LOVELL, R., and Abt, G. (2013). Individualization of Time-Motion Analysis: A case-cohort example. International Journal of Sports Physiology and Performance, 8, 456-458. 7. Buchheit M, Solano R, Millet GP. Heart-rate deflection point and the second heart-rate variability threshold during running exercise in trained boys. Ped Exer Sci 2007; 19(2): 192-204. 8. Dupont et al. (2004). The effect of in-season, high-intensity interval training in soccer players. Journal of strength and conditioning research; 18 (3) pp. 584-9. 282 Title of Project: Neuroplasticity, pain and movement (FOR Code/s): 110317; 110321; 110603; 110903 Supervisor: Professor Lucy Chipchase Contact: [email protected] (Phone 4620 3758) Co-supervisor: Contact: Location of Project: BRAiN-Laboratory, School of Science and Health, Campbelltown Campus Project Background The Brain Rehabilitation and Neuroplasticity Unit (BRAiN-U) aims to answer key basic science and clinical questions in the field of neuroplasticity, pain and motor learning. In addition, we aim to develop new brain-based treatments for neurological and musculoskeletal disorders. I am particularly interested, and currently conducting research, in a range of common clinical conditions including acute and chronic pain, anterior knee pain, knee osteoarthritis, and tennis elbow. I am also interested in how brain stimulation and therapeutic techniques can be used to enhance skill acquisition in sport (e.g. golf) and after injury. I have a range of projects available and am also open to discussing your ideas and suggestions for research in this field. Aim of Study: My research priorities are: 5. To understand the way the healthy human brain can change and adapt throughout life through investigation of neuroplastic mechanisms. 6. To understand how neuroplasticity is altered in musculoskeletal (chronic low back pain, osteoarthritis, tennis elbow) disorders. 7. To develop and test new and existing therapies that drive beneficial brain plasticity to alleviate pain and improve function in musculoskeletal disorders 8. To enhance learning in the healthy brain, learning of sports specific skills, re-learning of skills that have been lost through illness or injury, using non-invasive brain stimulation and other therapeutic techniques. Methods: The BRAiN-U laboratory is fully functional with two transcranial magnetic stimulation units, EMG, a neuronavigation system, transcranial direct current, acute pain models, motor learning tasks and quantitative sensory testing units. The methods would be selected based on each project. I have supervised over 20 Honours students, all of whom have achieved first class Honours. Six of these have progressed to PhDs being competitive for scholarships. Currently, our laboratory has a number of Honours and PhD students so you will work in a very engaging environment and have opportunities to gain skills and knowledge in the measurement and analysis of brain plasticity data and other specific measurement tools as well as working and collaborating with a number of research higher degree students and academics. I have a very collegial approach to mentoring and supporting beginning researchers. I aim to ensure that the work you conduct will be presented at conferences and be of a standard to submit for publication. My projects will suit students from a health science program (e.g. physiotherapy, exercise science, medicine) or a biomedical science with a strong drive to succeed and to learn from leaders in the field. Ethics Application Requirements: I have program ethics (#H10184) that covers a wide variety of projects. Amendments for individual projects would need to be sought. Key References: 283 8. 9. 10. 11. 12. 13. 14. Chipchase LS, Schabrun SM and Hodges PW (2011): Corticospinal excitability is dependent on the parameters of peripheral electrical stimulation: a preliminary study. Archives of Physical Medicine and Rehabilitation 92 (9): 1423-1430 [IF 2.284, 10/62 Rehabilitation journals] Chipchase LS, Schabrun SM and Hodges PW (2011): Peripheral electrical stimulation to induce cortical plasticity: a systematic review of stimulus parameters. Invited Review. Clinical Neurophysiology 122: 456-463 [IF 3.406, 46/192 of clinical neurology journals] Schabrun SM and Chipchase LS (2012): Priming the brain to learn: the future of therapy? Manual Therapy 17: 184-186. [IF 1.885, 18/62 Rehabilitation journals) Andrews R, Schabrun SM, Ridding MC, Galea M, Hodges PW and Chipchase LS (2013): Motor electrical stimulation and corticospinal excitability: the effect of application time. Journal of Neuroengineering and Rehabilitation 10: 51 (IF 2.57; 7/63 Rehabilitation journals; 22/79 Biomedical Engineering journals) Schabrun SM, Ridding MR and Chipchase LS (2013): An update on brain plasticity for physical therapists. Physiotherapy Practice and Research 34: 1-8. Adam K, Peters S and Chipchase L (2013): Knowledge, skills and professional behaviours required by occupational therapist and physiotherapist beginning practitioners in work-related practice: a systematic review. Aust J Occ Ther 60: 76-84 [IF 0.677] Chipchase LS, Schabrun SM, Cohen L, Hodges PW, Ridding MC, Rothwell J, Taylor J and Ziemann U (2012): A checklist for assessing the methodological quality of studies using transcranial magnetic stimulation to study the motor system: an international consensus study. Clinical Neurophysiology 123 (9): 1698-1704. [IF 3.406, 46/192 of clinical neurology journals] 284 Title of Project: Enhancing visual search and awareness in athletes using stroboscopic glasses (FOR Code/s): Supervisor: Dr. Kylie Steel Contact: [email protected] Co-supervisor: Dr. Sera Dogramaci Contact: [email protected] Location of Project: UWS Werrington Campus; NSW Institute of Sport, Sydney Olympic Park Project Background Stroboscopic glasses consist of LCD lenses that alternate between clear and opaque states, effectively restricting visual information and feedback1-3. The effect is to force the athlete to place more effort in attending, extracting, and searching for information in the performance environment when vision is provided, and to learn to predict/anticipate the movements of objects and other athletes when vision is partially or completely removed for periods of time3. Initial studies have reported that when athletes train with the stroboscopic glasses, the experience raises mental effort, making better use of all capacities; as well as help develop skill. Anecdotally, when then entering competition environments, the experience has been described as making ‘the game feel like it is moving slower’, and ‘making anticipation become easier’3. Benefits from use and integration have been reported from a single 5 minute training session1; perhaps even if only to raise athlete confidence. The point here, that minimal-large exposure will provide benefit and without any expected detriment to athletes. Aim of Study: The objectives of the study are to implement stroboscopic glasses successfully into elite athlete training; understand the impact of stroboscopic glasses on competition performance; and enhance athlete visual skills, particularly visual search and awareness. Methods: Athletes will complete standard reaction time, anticipation, and game-specific awareness testing, before integrating the glasses into specific training exercises aimed at improving visual tracking, anticipation and spatial awareness. Position specific training exercises will be devised and applied, based on coach advice/recommendation. Performance indices during competition will also be monitored, supported by post-match analysis. Follow-up post-training measures will occur to enable a pre-post assessment on standard tests and ‘in-field’ performance. Ethics Application Requirements: This study has been approved by the Australian Institute of Sport Ethics Committee (No. 20140404). Key References: 1. Smith, T. Q., & Mitroff, S. R. (2012). Stroboscopic training enhances anticipatory timing. Int J Ex Sci, 5(4), 344-353. 2. Appelbaum, L. G., Cain, M. S., Schroeder, J. E., Darling, E. F., & Mitroff, S. R. (2012). Stroboscopic visual training improves information encoding in short-term memory. Atten Percept Psychophys, 74, 1681-1691. 3. Clark, J. F., Ellis, J. K., Bench, J., Khoury, J., & Graman, P. (2012). High-performance vision training improves batting statistics for University of Cincinnati baseball players. PLoS ONE, 7(1), 1-6. NOTE: There are several other project opportunities at NSWIS in 2015. Please contact Kylie Steel. 285 Title of Project: The use of simulation training to accelerate the rate of skill acquisition in technical tasks (FOR Code/s): Supervisor: Dr. Kylie Steel Contact: [email protected] Co-supervisor: Dr. Sera Dogramaci Contact: [email protected] Location of Project: UWS Werrington Campus; NSW Institute of Sport, Sydney Olympic Park Project Background The pressures associated with sport has seen athletes underperforming during competition due to an inability to execute the correct technical skill, including not being able to pass or shoot the desired distance. Simulation training may allow athletes to develop the necessary skills required before transferring these skills into competition, with several sports already integrating such training into their skill acquisition program, for example, ball projection machines in cricket, baseball, volleyball and tennis (Pinder et al. 2011). The time taken to master a skill varies between individuals, which not only includes the physical aspect, but also the cognitive aspect associated with the task. This may result in athletes entering competition without being optimally prepared to compete. Aim of Study: The aims of the study are to examine if technical skill simulation equipment replicates the skill it is designed to simulate, and to identify how much training is required on the equipment to see improvements in the competition environment. Methods: Subjects will undertake a pre-test of physical skills in the competition environment to establish a baseline. This will be specific to the sport chosen. Subjects will then be split into a control or treatment group: control group partakes in regular scheduled training sessions, treatment group given detailed instruction and feedback on tasks assigned in addition to regular scheduled training sessions. After this training phase, post-testing on the same pre-test skills are undertaken to determine the degree of change in performance from training to competition. Retention testing of the physical skills will also be undertaken. Ethics Application Requirements: Ethics Approval has not been given yet for this project but will be applied for. Key References: Pinder, R. A., Renshaw, I., Davids, K. & Kerhervé, H. (2011). Principles for the use of ball projection machines in elite and developmental sport programmes. Sports Medicine. 41 (10); 793-800. NOTE: Several other projects are available with NSWIS in 2015. Please contact Kylie Steel. 286 Title of Project: Does expertise influence decision accuracy and response time when observing brief visual displays of biological motion sport? (FOR Code/s): 4066 Supervisor: Dr Kylie Steel Contact: [email protected] Co-supervisor: Dr Rachel Robbins Contact: [email protected] Location of Project: Penrith, Campbelltown, Bankstown Project Background: A significant body of research exists that examines biological motion in a variety of contexts, e.g., security, medicine, computer science and perceptual psychology. This research has found that individuals can identify familiar individuals (Cutting & Kozlowski, 1977), gender (Barclay, Cutting, & Kozlowski,1978), deception ((Runeson & Frykholm, 1981), and emotion (Pollick, Lestou, Ryu, & Cho, 2002). In these situations observers use relative information (temporal and spatial) to formulate responses and often use global processing to achieve this goal. Preliminary research suggests discrimination is achievable as is trainability in sport people (Ellem, 2013) however no research, to our knowledge, has investigated the impact of sports expertise and the visual cues sports people use to identify team-mates from <500msec video clips (Steel et al, 2010). Examination of these two factors (expertise/ visual cues) would provide the base level information required for training purposes not only in this domain but others, e.g., military. Aim of Study: Project 1; To examine the expertise of sports people when discriminating sports people from nonsports people using brief visual displays of biological motion examples. Project 2; To examine the visual cues sports people extract when discriminating sports people from non-sports people using brief visual displays of biological motion examples. ***IMPORTANT: This project can accommodate two-three students. Methods: Participants (N=15+) within this study will be required to: 1. Observe video footage of individuals performing, e.g., a throwing, kicking, catching, running skill. 2. They will then be required to identify whether the observed individual is a sports person or not. 3. Comparison of accuracy rates will be determined based on expertise and cues used to make decisions. Ethics Application Requirements: Human ethics required. Key References: 1. Barclay, C. D., Cutting, J. E., & Kozlowski, L. T. (1978). Temporal and spatial factors in gait perception that influence gender recognition. Perception and Psychophysics, 23(2), 145-152. 2. Cutting, J. E., & Kozlowski, L. T. (1977). Recognising friends by their walk; Gait perception without familiarity cues. Bulletin of the Psychonomic Society, 9(5), 353-356. 3. Robbins, R., & McKone, E. (2003). Can holistic processing be learned for inverted faces? Cognition, 88, 79-107. 4. Runeson, S., & Fryholm, G. (1981). Visual perception of lifted weight. Perceptual and Motor Skills, 7(4), 733-740. 5. Steel, K. A., Adams, R. D., Canning, C, G., Eisenhuth, J. (2010). The Team-Mate Identification (TM-ID) test; Effect of participant and situation familiarity on response accuracy and latency. International Journal of Sport Science and Coaching, 5 (2), 281-290. NOTE: I am also happy to discuss other skill acquisition (motor learning and control) projects that may be of interest to you. 287 Title of Project: Observational learning and the side step (FOR Code/s): 4066 Supervisor: Dr Kylie Steel Contact: [email protected] Co-supervisor: Ingvars Birznieks (UNSW) Contact: TBA Location of Project: Penrith, Campbelltown Project Background: Sport participants acquire many motor (movement) and perceptual-cognitive (decisions-making) skills during their athletic development. However many participants and coaches will trade-off some skills based on skilled performance of others, i.e., if you are fast and skilled at kicking you may not bother to improve your agility (side-stepping). As a result this skill remains a deficit in the participants skill set and may result in non-selection in teams at higher competitive levels. Whilst traditional instructional and practice methods are useful when learning movement skills, some participants may benefit from additional approaches to movement learning such as ‘Self-asmodel’ (Dowrick, 1999). ‘Self’ based models use a series of visual images of the participant performing the entire skill, but only the best and most appropriate examples of that skill. The ‘Self’ based method has been used successfully in recent times to improve the kicking ability of Australian Football League players (Steel, et al., 2010). Participants in these studies observed visual images on a daily basis over a two-three week period. Their best kicks served to demonstrate to them the type of kick they wished to use in game situations. Given the success of this methodology within this experimental group it is suggested that such a method may have similar effects in additional athletic groups. Therefore the purpose of this study is to determine whether ‘Self’ can be used to improve the deceptive movements skills of team sport participants. Aim of Study: The aims of this study include the design of a self-based training method to improve the effectiveness of deceptive movements in team-sports participants.***IMPORTANT: This project can accommodate two students in addition to being applied to alternate populations and skills, e.g., stroke patients and reach and grasp. Methods: Participants within this study will be required to: 1. Participants will be filmed while they perform a series of deceptive movements to either the left (10) and/or right (10) of an obstacle. 2. The footage will then be used to provide a learning stimulus for the participants. 3. The participants will view the learning stimulus every day for one week. After this period the participants will be retested to determine whether improvement has occurred on one or both sides. Ethics Application Requirements: Human ethics required. Key References: 1. Dowrick, P. W. (1999). A review of self modelling and related interventions. Applied & Preventative Psychology. 8: 23-39. 2. Steel, K. A., Coulson, S., Adams, R. D., & Canning, C, G. (2010). Self-as-a-model training of left foot AFL punt kicking in two cases using reversed video footage of the player’s right foot kicks. Proceedings of the 2010 ACSMs Sports Medicine Australia Conference, Port Douglas, Nov 4-6. NOTE: I am also happy to discuss other skill acquisition (motor learning and control) projects that may be of interest to you. 288 Title of Project: Lower limb injury and bushwalking shoes: Barriers and facilitators for ‘green exercise’ (FOR Code/s): 11 Medical and Health Sciences, 110604 Sports Medicine, 730220 Injury Control, 730299 Public Health Supervisor: Dr Stef Penkala Contact: Ph 4620 3742, email [email protected] Location of Project: Campbelltown Project Background Mental health is one of Australia's National Health Priority Areas. In Australia in 2007, 14.4% (2.3 million) of people aged 16-85 years were reported to have a lifetime anxiety disorder with symptoms over a 12 month period (1). By 2030, anxiety/depression and ischaemic heart disease are predicted to be two of the three leading causes of illness globally (3). Effective and sustainable interventions to manage anxiety disorders are needed to optimise well-being and opportunities to engage in productive social and working lives. Self-help interventions such as exercise can be positive (2). Findings from a developing body of research indicate that physical activity in the natural environment, ‘green exercise’ has additional positive psychological benefits including reductions in anxiety (4,5). In Australia, bushwalking is a viable form of ‘green exercise’ without the financial burden of gym or sports club membership and fees. Additional benefits of the visual environment can profoundly affect the sense of physical and mental well-being. However, research indicates that a significant number of adults as well as children report foot and shoe-related problems which can hinder daily physical activities like walking (6,7). ‘Underfoot’ events including slips, trips, falls and ankle spranis are the most commonly reported in outdoor ‘adventure’ sports (8). Optimal shoe recommendations are essential to ensure shoes meet the demands of the individual and activity. Despite the wide range of bushwalking shoes available, little is known about footwear literacy/shoe attributes which can be beneficial or detrimental for foot heath, or the contribution to green exercise participation. Aim of Study: 1) To investigate shoe attributes commonly recommended by adventure store staff, and experienced bushwalkers for people purchasing shoes for bushwalking. 2) To investigate peoples footwear experience when participating in green exercise, and the facilitators and barriers ( i.e. shoe-related foot problems, footwear literacy). Methods: Focus groups and semi-structured interviews will be conducted with adventure store staff, experienced bushwalkers and novice bushwalkers. Responses will be transcribed verbatim and categorised to develop a meaningful data framework using a constant comparison technique. Ethics Application Requirements: NEAF Required Key References: 1) Australian Bureau of Statistics (2007) National survey of mental health and wellbeing. Cat No 4326.0 2) Merom et al (2008) Promoting walking as an adjunct intervention to group cognitive behavioural therapy for anxiety disorders – A pilot group randomized trial. Journal of Anxiety Disorders 22: 959-968 3) Mathers CD, Loncar D (2006) Projections of Global Mortality and Burden of Disease from 2002 to 2030. PLoS Med 3(11): e442. doi:10.1371/journal.pmed.0030442 4) Mackay GJ & Neill JT (2010) The effect of “green exercise” on state anxiety and the role of exercise duration, intensity and greenness: a quasi-experimental study. Psychology of Sport and Exercise 11: 238-245 5) Pretty (2005) The mental and physical health outcomes of green exercise. International Journal of Environmental Health Research. 15(5): 319 – 337 6) Garrow, A. P., Silman, A. J., & Macfarlane, G. J. (2004). The Cheshire Foot Pain and Disability Survey: a population survey assessing prevalence and associations. Pain, 110(1-2), 378-384. 7) Penkala S, Harris L, Hunt A and Naughton G (2010) Foot complaints of children aged four to twelve years, sex differences and activity – a cross-sectional survey of parents. Journal of Science and Medicine in Sport 12(2): 107 8) Bentley TA, Cater C and Page SJ. Adventure and ecotourism safety in Queensland: Operator experiences and practice. Tourism Management 31 (2010) 563–571 289 Immunology 290 Title of Project: To investigate the role of SMG1 in innate immune signalling. (FOR Code/s): 060111 Signal Transduction, 110707 Innate Immunity, 111201 Cancer Cell Biology, 111206 Haematological Tumours Supervisor: Dr Tara Roberts Contact: [email protected] Co-supervisor: Dr Uda Ho (TBC) Contact: (02) 87389020 Location of Project: The Ingham Institute for Applied Medical Research. Project Background SMG1 is a member of the PI-3 kinase like kinase (PIKK) family of proteins which include ATM, DNA-PK and mTOR. Members of this family have well-characterised roles in responses to cellular stress including DNA damage and nutrient deprivation. We recently described a novel role for SMG1 as a tumour suppressor. Decreased SMG1 protein expression led to increased development of cancer, particularly lymphomas and lung adenocarcinomas. SMG1 loss also increased basal inflammation and oxidative damage to tissues prior to tumour development. These data suggest that SMG1 may contribute to cancer development, at least partially, by promoting inflammation. Aim of Study: To understand how loss of SMG1 alters innate immune responses. This study will focus on determining if and how SMG1 loss alters toll-like receptor mediated responses and inflammasome activation. Methods: This project will utilise a range of methods including mammalian cell tissue culture, siRNA knockdown, cellular activation assays (ELISA, Flow cytometry), cell signalling analysis (western blotting, immunofluorescence) as well as isolation and analysis of cells from genetically modified mice. Ethics Application Requirements: This project already has animal ethics and OGTR approval. Key References: Background to project: Roberts TL, Ho U, et al. (2013) Smg1 haploinsufficiency predisposes to tumor formation and inflammation. Proc Natl Acad Sci U S A 110(4):E285-294. Hanahan D & Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646-674. Li N, Grivennikov SI, et al. (2011) The unholy trinity: inflammation, cytokines, and STAT3 shape the cancer microenvironment. Cancer Cell 19(4):429-431. Indication of techniques: Roberts TL, Dunn JA, et al. (2011) The immunostimulatory activity of phosphorothioate CpG oligonucleotides is affected by distal sequence changes. Mol Immunol 48(8):1027-1034. Roberts TL, Idris A, et al. (2009) HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science 323(5917):1057-1060. 291 Medical Microbiology 292 Title of Project: Antibacterial properties of emu oil. (FOR Code/s): 110801 Medical Bacteriology Supervisor: Dr Poonam Mudgil Contact: [email protected], Ph: 4620 3945 Co-supervisor: Prof John Whitehall Contact: [email protected], Ph: 4620 3787 Location of Project: School of Medicine, Campbelltown Campus Project Background Bacterial infections are common in children and are generally treated with antibiotics. Antibiotics carry the risk of systemic side effects which can be particularly serious in children.1 Increasing development of antibiotics resistance among bacterial pathogens poses a great challenge and calls for testing compounds that are natural and safe and can help in combating antibiotics resistance. Emu oil, extracted from the fat tissues of Emu birds, has traditionally been used by native Australian Aboriginals to treat wounds, sores, pain and arthritis.2 Its anti-inflammatory properties are known3,4 but its antimicrobial properties are yet to be explored. Emu oil contains oleic acid as the major fatty acid.5 Our previous research has shown oleic acid to be antibacterial against both Gram positive and Gram negative bacteria. Hence emu oil is likely to be antibacterial. This project will investigate the antibacterial properties of emu oil to explore its potential as an alternative antibacterial treatment option. This can help in reducing antibiotics usage and antibiotics resistance in clinical pathogens. Aim of Study: To test the antibacterial efficacy of emu oil against clinical bacterial isolates. Methods: Antibacterial effects of emu oil against a number of clinical bacterial isolates will be tested in-vitro using Muller Hinton Broth. Minimum inhibitory concentration of emu oil will be determined using broth dilution technique. Scanning electron microscopy will be used to image bacterial cells to observe morphological damages caused by emu oil. Ethics Application Requirements: N/A Key References: 1 Clinc Pediatr (Phila), 1998, 37:645 2 Whitehouse et al. Inflammopharmacology 1998; 6: 1–8. 3 Snowden & Whitehouse. Inflammopharmacology 1997; 5: 127–32. 4 Lindsay et al. Br. J. Nutr. 2010; 104:513–19. 5 Beckerbauer et al. Poult. Sci. 2001; 80: 187–94. 293 Neurosciences 294 Title of Project: The impact of chronic neuroinflammation on the basal forebrain cholinergic system: implications on Alzheimer’s disease (FOR Code/s): Supervisor: Dr Erika Gyengesi Contact: [email protected] Co-supervisor: Prof Gerald Muench Contact: [email protected] Location of Project: Campbelltown, School of Medicine, Building 30 Project Background In the last century, the average life span has increased from 47 to 78. It is projected that by the year 2025 that 20% of the population will be over the age of 65. Alzheimer’s disease (AD) is the most common form of dementia of the elderly that causes problems with memory, thinking and behavior progressively declining with age. Previously, the central nervous system was considered to be an immunologically privileged organ, where immune responses are highly restricted and therefore it escapes inflammatory assault. Chronic neuroinflammation is one of the major contributor factors in the development of the pathogenesis of AD. This project will investigate the relationship between neuroinflammation and its effects on the anatomy of the basal forebrain cholinergic system in IL-6 overexpressing mice during their life span, analyzing anatomical changes and measure neuroinflammation markers, cell loss and synaptic degeneration. Finally, we will test whether the brain-permeable anti-inflammatory plant compound, curcumin is able to prevent and restore the age related damage caused by chronic neuroinflammation. The ultimate goal of this project is to advance our knowledge about changes in the aging brain caused by neuroinflammation and investigate the link between neuroinflammation and the degeneration of the cholinergic system. Aim of Study: The specific aims of this study are: 1. To study the effects of neuroinflammation on the morphological structure of the basal forebrain cholinergic system and the interconnected areas using anatomical techniques, immunohistochemistry and microscopy. 2. To investigate the effects of a high bioavailable preparation of the anti-inflammatory compound curcumin on brain inflammation and neurodegeneration. Methods: Specific aim 1. To study the effects of neuroinflammation on the morphological structure of the basal forebrain cholinergic system and its interconnected areas. Research plan: Immunohistochemical investigation of the expression of cholinergic cell bodies and neuritis, calciumbinding protein containing neurons (parvalbumin), IL-6, GFAP, myelination and overall cell numbers will be carried out on both GFAP-IL6 transgenic mice and their wild type littermates. GFAP-IL6 heterozygote transgenic and wild type mice of age from 3 to 12 months (n=7) will be euthanized and transcardinally perfused. Brains will be removed and sectioned at 40 µm with a cryostat the next day in 7 series. Sections will be collected from the entire brain from the olfactory bulb to the cerebellum and analysed by using a research microscope equipped with MBF Biosciences StereoInvestigator to achieve design-based, un-biased quantitative results. On the first series of sections, modified Nissl staining will be performed. Sections of series 2 to 6 will be treated with the following primary antibodies followed by secondary antibodies to visualise cholinergic, parvalbumin, secretagogin, GFAP, IL-6 and IL-6 receptor expressing cells and glia. Myelin silver staining, first described by Gallyas, will be carried out on the last series to visualise myelinated axons. Specific aim 2. To investigate the effects of anti-inflammatory compound curcumin on brain inflammation, neurodegeneration and synaptic decline. Research plan: To test the effects of curcumin on our animal model, a group of GFAP-IL6 heterozygous mice (n=8/group, equal distribution of gender) will be treated with Longvida curcumin in the drinking water (Longvida, Vendure Sciences). Levels of curcumin will be measured from the blood and the brain tissue by using HPLC-MS. Animals will be sacrificed for immunohistological experiments described at aim 1, at age 3, 6, 9 and 12 months. Results will then be compared between the treated, the untreated and wild type groups (using our results from Aim 1 and 2). Ethics Application Requirements: Animal Research Authority application has been approved by the UWS Animal Ethics committee to conduct animal research, as documented in Animal Research and Teaching Proposal Number: A10057; Title: Anatomical and behavioural studies of the rodent brain during neuroinflammation in IL6-GFAP mice; 295 At the following site: Animal holdings - C Building 30 SoM animal holdings Key References: Key References: 1 Ikegami, S. Behavioral impairment in radial-arm maze learning and acetylcholine content of the hippocampus and cerebral cortex in aged mice. Behav Brain Res 65, 103-111 (1994). 2 Heyser, C. J., Masliah, E., Samimi, A., Campbell, I. L. & Gold, L. H. Progressive decline in avoidance learning paralleled by inflammatory neurodegeneration in transgenic mice expressing interleukin 6 in the brain. Proc Natl Acad Sci U S A 94, 1500-1505 (1997). 3 Campbell, I. L. et al. Transgenic models to assess the pathogenic actions of cytokines in the central nervous system. Mol Psychiatry 2, 125-129 (1997). 4 Campbell, I. L. & Powell, H. C. Role of Cytokines in Demyelinating Disease Studied in Transgenic Mice. Methods 10, 462-477 (1996). 5 Campbell, I. L., Kay, T. W., Oxbrow, L. & Harrison, L. C. Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. J Clin Invest 87, 739-742, doi:10.1172/JCI115055 (1991). 6 Campbell, I. L., Eddleston, M., Kemper, P., Oldstone, M. B. & Hobbs, M. V. Activation of cerebral cytokine gene expression and its correlation with onset of reactive astrocyte and acute-phase response gene expression in scrapie. J Virol 68, 2383-2387 (1994). 7 Campbell, I. L. & Chiang, C. S. Cytokine involvement in central nervous system disease. Implications from transgenic mice. Ann N Y Acad Sci 771, 301-312 (1995). 8 Campbell, I. L. et al. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci U S A 90, 10061-10065 (1993). 9 Campbell, I. L. Structural and functional impact of the transgenic expression of cytokines in the CNS. Ann N Y Acad Sci 840, 83-96 (1998). 10 Fuller, S., Munch, G. & Steele, M. Activated astrocytes: a therapeutic target in Alzheimer's disease? Expert Rev Neurother 9, 1585-1594, doi:10.1586/ern.09.111 (2009). 11 Maczurek, A., Shanmugam, K. & Munch, G. Inflammation and the redox-sensitive AGE-RAGE pathway as a therapeutic target in Alzheimer's disease. Ann N Y Acad Sci 1126, 147-151, doi:10.1196/annals.1433.026 (2008). 12 Steele, M., Stuchbury, G. & Munch, G. The molecular basis of the prevention of Alzheimer's disease through healthy nutrition. Exp Gerontol 42, 28-36, doi:10.1016/j.exger.2006.06.002 (2007). 13 Huber, A., Stuchbury, G., Burkle, A., Burnell, J. & Munch, G. Neuroprotective therapies for Alzheimer's disease. Curr Pharm Des 12, 705-717 (2006). 14 Stuchbury, G. & Munch, G. Alzheimer's associated inflammation, potential drug targets and future therapies. J Neural Transm 112, 429-453, doi:10.1007/s00702-004-0188-x (2005). 15 Munch, G. et al. Microglial activation induces cell death, inhibits neurite outgrowth and causes neurite retraction of differentiated neuroblastoma cells. Exp Brain Res 150, 1-8, doi:10.1007/s00221-003-1389-5 (2003). 296 Title of Project: Astrocytic regulation of brain waves (FOR Code/s): 110903 Neurosciences Supervisor: Dr Yossi Buskila Contact: [email protected] Co-supervisor: Contact: Location of Project: Campbelltown campus Project Background The rhythmic voltage fluctuations generated through the synchronous activity of neuronal networks are thought to be involved with many physiological processes such as selective attention, sleep and memory. The aim of this project is to investigate the potential role for astrocytes, which are the most prevalent non-neuronal cell type in the brain, in mediating the transition between different frequencies of these oscillations. Furthermore, this study will provide important insights into the bi-directional communication that astrocytes establish with neurons, which is one of the most intriguing questions in neurobiological research today. Aim of Study: In this project we aim to discover the astrocytic-neuronal interactions that regulate neuronal synchronous activity. Methods: Imaging and Electrophysiological recordings from brain slices. Ethics Application Requirements: ACEC approval A10588 Key References: Poskanzer, K. E. & Yuste, R. Astrocytic regulation of cortical UP states. PNAS 108, 18453–8 (2011). 297 Title of Project: The impact of traumatic brain injury on neuronal viability (FOR Code/s): 110903 Neurosciences Supervisor: Dr Yossi Buskila Contact: [email protected] Co-supervisor: Contact: Location of Project: Campbelltown campus Project Background A Traumatic Brain Injury or TBI is an injury to the brain caused by a blow to the head or other external force, which may cause rapid movement of the brain inside the skull. As a result the brain may be torn, stretched, penetrated, bruised or become swollen. TBI often results in secondary injuries, which arise due to the brain's reaction to the first injury. These further injuries include brain swelling and haemorrhaging, which puts pressure on brain tissue and restrict oxygen supply to other parts of the brain leading to cell death. Often treatment of a traumatic brain injury is focused on controlling the secondary effects to prevent further damage, however the processes which controls the viability and sensitivity of neurons to the secondary effects is still unknown. Aim of Study: The aim of this project is to test the long-term viability of different cell types in the brain following TBI, using a new incubation system for brain slices, named the Braincubator. Methods: Imaging and Electrophysiological recordings from brain slices. Ethics Application Requirements: ACEC approval A9452 Key References: Buskila, Y., Breen, P. P., Tapson, J., van Schaik, A., Barton, M., & Morley, J. W. (2014). Extending the viability of acute brain slices. Scientific Reports, 4, 4–10. doi:10.1038/srep05309 298 Title of Project: Signal processing in afferent fibres of the peripheral nervous system (FOR Code/s): 110903 Neurosciences Supervisor: Dr Yossi Buskila Contact: [email protected] Co-supervisor: Prof. André van Schaik Contact: [email protected] Co-supervisor: Prof. John Morley Contact: [email protected] Location of Project: Campbelltown campus Project Background Sensory systems in mammals use action potentials (spikes) for communication. In the peripheral nervous system, mechanoreceptors, such as Merkel cells, transduce tactile stimuli into spikes that then propagate into the central nervous system and give rise to the sense of touch. Although Merkel cells were discovered more than 100 years ago, the cellular and molecular mechanisms underlying tactile transduction in Merkel discs (Merkel cell-neurite complexes) remain unclear. Recent studies revealed that Merkel cells generate calcium spikes that lead to vesicular release and activation of the associated slowly adapting (SAI) Aβ afferent fibre, however it is unknown how the signal is further encoded in the unmyelinated segments of the fibre and at the heminodes, special structures on the SAI fibre that integrates the neuronal signals and capable of initiating a spike. Aim of Study: The aim of this project is to monitor the information flow and signal processing in the peripheral nervous system, specifically in the unmyelinated segments of tactile afferent fibres. Methods: High-speed Imaging and Electrophysiological recordings. Ethics Application Requirements: ACEC approval A9452 Key References: Ikeda, R., Cha, M., Ling, J., Jia, Z., Coyle, D., & Gu, J. G. (2014). Merkel cells transduce and encode tactile stimuli to drive Aβ-afferent impulses. Cell, 157(3), 664–75. doi:10.1016/j.cell.2014.02.026 Lesniak, D. R., Marshall, K. L., Wellnitz, S. a, Jenkins, B. a, Baba, Y., Rasband, M. N., … Lumpkin, E. a. (2014). Computation identifies structural features that govern neuronal firing properties in slowly adapting touch receptors. eLife, 3, e01488. doi:10.7554/eLife.01488 299 Title of Project: Effects of siesta on blood pressure and muscle sympathetic nerve activity (FOR Code/s): 110602, 110901 Supervisor: Dr. Chloe Taylor Contact: [email protected] Co-supervisor: Prof. Vaughan Macefield Contact: v.macefield.uws.edu.au Location of Project: Campbelltown Project Background It is well established that the incidence of cardiovascular events (such as myocardial infarction) is highest in the morning hours after waking (Muller et al., 1989). It has also been reported that a secondary peak occurs in the afternoon, which has been attributed to daytime napping or ‘siesta’ in some populations. Whilst Bursztyn and Stessman (2005) reported an increased risk of mortality in those who partake in siestas, the cause is currently not clear. Previous studies indicate a link between the high prevalence of cardiovascular events in the morning and increases in blood pressure and sympathetic activity at this time. We therefore hypothesise that similar mechanisms maybe involved when waking from daytime sleep. Aim of Study: To determine the effects of awakening from daytime sleep on blood pressure and muscle sympathetic nerve activity. Methods: 12 participants will be recruited for the study. Each participant will be required to attend the laboratory on one afternoon. Participants will lie in a supine position in a quiet room while continuous measurements of blood pressure, heart rate, respiration and muscle sympathetic nerve activity (MSNA) will be recorded. Microneurography is an invasive technique for the direct measurement of MSNA. It involves the insertion of a fine needle electrode into the common peroneal nerve (in the leg, at the level of the fibular head). Participants will wear a blindfold and be asked to relax whilst remaining in a supine position. Lack of response (via handheld push button) to a short audio cue will be used to determine sleep. After a minimum of 20 mins sleep, the participant will be woken by an alarm and the blindfold will be removed. Physiological variables will be measured for a further 30 mins following waking. Additional experiments will be performed if sleep is not initiated. Ethics Application Requirements: Ethical approval has been granted (H9577) Key References: Bursztyn, M. & Stessman, J. (2005). The siesta and mortality: twelve years of prospective observations in 70-year-olds. Sleep, 28: 345-347. Muller, J. E., Tofler, G. H. & Stone, P. H. (1989). Circadian variation and triggers of onset of acute cardiovascular disease. Circulation, 79; 733-743. Muller, J. E., Tofler, G. H. & Verrier, R. L. (1995). Sympathetic activity as the cause of the morning increase in cardiac events. Circulation, 91: 2508-2509. 300 Field of Research: Molecular Physiology / Neuroscience (FOR Code/s): 1109, 0606, 1101, 0601 Title of Project: Defining Molecular Mechanisms Underlying Multiple Sclerosis Supervisor: Prof. Jens Coorssen Email: [email protected] Co-supervisor: Dr. Simon Myers Email: [email protected] Campus project is offered and conducted: Campbelltown Telephone: 46203802 Telephone: 46203383 Background (max 500 words) Multiple Sclerosis (MS) is a CNS disorder of as yet undefined aetiology. It has long been assumed to be an autoimmune disorder, and there is no doubt that such a component is an active part of the disease process and its progression. Nonetheless, it has also become apparent that this aspect alone does not necessarily explain the initiation/development of MS; a newer hypothesis holds that MS may first and foremost be a degenerative disorder, specifically an oligodendrocytosis. We are currently engaged in a research project to better distinguish between these aspects of MS using different mouse models as well as blood/white cell samples from human patients. The outcomes will be important in terms of enabling earlier and/or better identification of (i) MS patients; (ii) prognostic indicators; and (iii) new therapeutic targets. Aim of Study: Hypothesis – MS is fundamentally a degenerative disease. Aims - Use detailed proteomic or lipidomic analyses to better understand molecular changes occurring in mouse models of MS - Identify specific CNS changes; - Identify specific changes in white cells Specific details for an Honours project can be discussed and refined with a suitable candidate. Methods: We have well established protocols for tissue processing, protein and lipid extraction, and all aspects of (i) proteomic analyses using a refined, quantitative 2D gel approach; and (ii) lipidomic analyses using a refined, quantitative high performance thin layer chromatography approach. Ethics Application Requirements: Both human (hospital) and animal ethics approval are in place. 301 Field of Research: Molecular Physiology / Neuroscience (FOR Code/s): 1109, 0601, 0606 Title of Project: Examining Molecular Mechanisms Underlying Ca2+ Triggered Neurotransmitter Release Supervisor: Prof. Jens Coorssen Email: [email protected] Telephone: 46203802 Co-supervisor: Dr. Chandra Malladi Email: [email protected] Telephone: 46203813 Campus project is offered and conducted: Campbelltown Background (max 500 words) Ca2+ triggered release of neurotransmitters (i.e. regulated synaptic vesicle exocytosis) is the process underlying basic central nervous system functions such as learning and memory. This process is known to be disturbed in debilitating disease including depression, epilepsy, and schizophrenia. Understanding the essential molecular mechanisms of exocytosis is thus a rational approach to addressing such disorders. Aim of Study: Although the basic pathway leading to neurotransmitter release has been established, the current challenge is to identify components that mediate each stage [1, 2]. Using a bias-free small-molecule based approach coupled with molecular/functional analysis, our laboratory has previously identified several proteins and lipids as either critical or modulatory components [3-6]. We now aim to test the roles of these candidates utilising an in vitro neurotransmitter release assay. To this end, this project aims to: 1) Establish an in vitro synaptic vesicle exocytosis assay to monitor several stages of neurotransmitter release; and 2) utilise the developed assay to understand the specific roles of critical proteins and lipids. Methods: Synaptosomes (functional nerve terminals) and synaptic vesicles will be isolated from rat brain using established protocols, and electron microscopy will be used to verify the purity of these preparations. A time-resolved Förster resonance energy transfer (FRET) based fluorescence assay to monitor exocytosis is under development. Well established molecular assays are available in the lab to monitor global changes in protein and lipid composition, as required [7, 8]. Preliminary results have established this as a feasible approach. Ethics Application Requirements: Approval from the UWS Animal Ethics Committee is in place. Key References: 1. Becherer, U. and J. Rettig, Vesicle pools, docking, priming, and release. Cell Tissue Res, 2006. 326(2): p. 393407. 2. Rogasevskaia, T.P. and J.R. Coorssen, A new approach to the molecular analysis of docking, priming, and regulated membrane fusion. J Chem Biol, 2011. 4(3): p. 117-136. 3. Furber, K.L., D.M. Brandman, and J.R. Coorssen, Enhancement of the Ca(2+)-triggering steps of native membrane fusion via thiol-reactivity. J Chem Biol, 2009. 2(1): p. 27-37. 4. Furber, K.L., K.T. Dean, and J.R. Coorssen, Dissecting the mechanism of Ca2+-triggered membrane fusion: probing protein function using thiol reactivity. Clin Exp Pharmacol Physiol, 2010. 37(2): p. 208-217. 5. Churchward, M.A. and J.R. Coorssen, Cholesterol, regulated exocytosis and the physiological fusion machine. Biochem J, 2009. 423(1): p. 1-14. 6. Churchward, M.A., et al., Specific lipids supply critical negative spontaneous curvature--an essential component of native Ca2+-triggered membrane fusion. Biophys J, 2008. 94(10): p. 3976-3986. 7. Wright, E.P., et al., Top‐down proteomics: Enhancing 2D gel‐electrophoresis from tissue processing to high sensitivity protein detection. Proteomics, 2014. 8. Churchward, M.A., et al., Copper (II) sulfate charring for high sensitivity on-plate fluorescent detection of lipids and sterols: quantitative analyses of the composition of functional secretory vesicles. J Chem Biol, 2008. 1(1-4): p. 79-87. 302 Title of Project: How does pain affect the brain? Supervisor: Dr Siobhan Schabrun Email: [email protected] Co-supervisor: Prof Thomas Graven-Nielsen Email: Campus/s project is offered and conducted: Campbelltown Background (200 words): How pain affects the brain is unclear, particularly when pain is prolonged (lasting days, weeks or months). We have recently acquired a new model (injection of nerve growth factor) that can induce pain in healthy individuals that lasts up to 14 days, mimicking the symptoms seen in patient populations such as low back pain or ‘tennis elbow’. Using this model it is possible to examine changes in the brain in the transition from acute to prolonged pain and begin to understand why some people recover after injury while others develop persistent pain syndromes. This information is essential if new treatments are to be developed that improve the symptoms of prolonged pain in the future. We anticipate that this study will result in conference presentations and a journal publication for the involved honours student. Aim of Study: This study aims to determine how brain function is altered during the transition from acute to prolonged pain. Methods: Healthy individuals will be recruited for this study. Individual’s will received repeated injection of nerve growth factor to induce prolonged elbow pain. Measures of brain activity, pain, motor function and learning will be made at a series of time-points using state of the art brain stimulation equipment. Ethics Application Requirements: Ethical approval has already been obtained. Key References: Hayashi K et al (2013): Repeated intramuscular injections of nerve growth factor induced progressive muscle hyperalgesia, facilitated temporal summation, and expanded pain areas. Pain 154: 2344-52. Nie H et al (2009): Temporal summation of pressure pain during muscle hyperalgesia evoked by nerve growth factor and eccentric contractions. Eur J Pain 13:704-10. 303 Title of Project: Brain-boosting to enhance learning Supervisor: Dr Siobhan Schabrun Email: [email protected] Co-supervisor: Dr Welber Marinovich Email: Campus/s project is offered and conducted: Campbelltown Background (200 words): Imagine a future where learning to move can be enhanced. The implications are far-reaching, from reduced rehabilitation times and quicker recovery after injury or illness, to improved training regimes for athletes and new strategies for maintaining function in old age. This future may soon be a reality. Non-invasive brain stimulation (NIBS) has enormous potential to revolutionise the way we learn. Indeed, preliminary studies from our group and others, suggest NIBS is effective at boosting learning. However, it is unclear when NIBS should be applied relative to training or therapy (i.e. should NIBS be applied before, during or after training/therapy) to give the greatest boost to learning. This study will be the first to investigate this important question. This work will have widespread implications for the design of NIBS therapies to boost learning in healthy individuals, athletes and individuals with neurological conditions such as stroke. We anticipate that this study will result in conference presentations and a journal publication for the involved honours student. Aim of Study: To determine whether non-invasive brain stimulation applied i) before, ii) during or iii) after training on a complex movement task has the greatest effect on learning. Methods: Healthy individuals will be recruited for this study. We will make measures of learning using a complex visuomotor transformation task and brain mechanisms using transcranial magnetic stimulation before and after non-invasive brain stimulation applied i) before, ii) during or iii) after a period of movement training. The three conditions will be assessed in three different experimental sessions. Ethics Application Requirements: Ethical approval has already been obtained. Key References: Schabrun, S. & Chipchase, L. Priming the brain to learn: the future of therapy? Man Therap 17(2012). Schabrun. Priming the brain to learn: the future of therapy? Man Therap, 2012. 304 Title of Project: Cold hypersensitivity in a model of spinal root avulsion injury (FOR Code/s): 1109 (110905 & 11096) Supervisor: Assoc Prof Peter Shortland Contact: [email protected] 4620 3804 Co-supervisor: Dr David Mahns Contact: [email protected] 4620 3784 Location of Project: UWS Campbelltown (Building 30) Project Background People who have traumatic injuries to the brachial or lumbosacral plexuses as a result of motor vehicle accidents often suffer from paralysis to the affected limb and extreme, intractable pain associated with the damaged roots. This includes a change of sensory perception in that mechanical or thermal stimuli that are normally perceived as innocuous are subsequently perceived as painful (allodynia) soon after the injury. The mechanisms that underlie these phenomena are incompletely understood. Using a recently developed model of avulsion injury we have explored the development of mechanical and heat hypersensitivity. However, people are most sensitive to cooling/cold temperature changes and so this project will explore the development of these issues in avulsion injuries. This project is part of a larger study exploring the mechanisms involved in avulsion injury pain. Aim of Study: 1. To determine the time course (onset, duration, resolution) of cold hyperalgesia 2. To determine the time course of (onset, duration, resolution) cold allodynia 3. To determine if avulsion injury changes the expression of receptors associated with cooling sensation in spinal ganglia. Methods: An experimental group will be subject to avulsion of the L5 spinal nerve roots (Chew et al. 2013). They will then undergo behavioural assessment by measuring the change in limb withdrawal latencies to temperature using a cold plate machine set at specific temperatures (15, 10, 4oC, to assess allodynia and hyperalgesia) or to evaporation to acetone on the sole of the foot (allodynia). This group’s behaviour will be compared to a naïve group. Behavioural training will commence 2 weeks prior to surgery and then once a day for the first week after injury and then twice a week for the next 6 weeks. Data will be collected and statistically analysed. At the end of the behavioural experiments, animals will be killed and the lumbar L4-5 spinal cord and L4-5 dorsal root ganglia will be removed and histologically processed using antibodies to TRPM8. Quantification of location and cell number will be performed and compared in experimental versus naïve groups. The student will gain an appreciation of scientific method, hypothesis testing, reading and interpreting relevant research literature. The student will receive appropriate training in animal behavioural testing, and histological methods (sectioning nervous tissue, immunohistochemistry, quantitative analysis, and fluorescence microscopy). Ethics Application Requirements: Ethics for animal experiments will be in place before project starts. Key References: 1. Chew DJ, Carlstedt T, Shortland PJ (2014) The effect of minocycline or riluzole treatment on spinal root avulsioninduced pain in adult rats. J. Pain 15: 664-675 2. Chew D.J., Murrell K., Carlstedt T., Shortland P.J. (2013) Segmental spinal root avulsion in the adult rat: a model to study avulsion injury induced pain. J. Neurotrauma 30: 160-172. 3. Knowlton WM, Palkar R, Lippoldt EK, et al. (2013) A sensory-labeled line for cold: TRPM8-expressing sensory neurons define the cellular basis for cold, cold pain, and cooling-mediated analgesia.J Neurosci. 33:2837-48 4. Su L, Wang C, Yu YH, Ren YY, Xie KL, Wang GL. (2011). Role of TRPM8 in dorsal root ganglion in nerve injuryinduced chronic pain. BMC Neurosci. 12:120. 305 Title of Project: Protein arginine methylation – a key player in cellular events (FOR Code/s): 0601 mainly (but others including 0605, 0607 and 1109 may also apply depending on project) Supervisor: Sabine C. Piller Contact: [email protected] or 46203354 Co-supervisor: TBA depending on project Contact: Location of Project: Campbelltown but some projects may involve work on other campuses including Hawkesbury, Parramatta or external as indicated below Project Background Protein arginine methylation is a post-translational modification like phosphorylation, acetylation and ubiquitination. Recent research and advances in technology have revived the initial research carried out on protein methylation in the early 1960ies (1), and protein arginine methylation has become one of the hot topics of research in a variety of fields including virology, cell biology and molecular mechanisms of disease as well as potential drug target development. Protein arginine methylation is a likely key modulator of cellular processes such as transcription, cell signalling, nuclear transport, ageing and cellular stress which has implications for a wide range of diseases including cancer, cardiovascular diseases, viral infections, lung disease and potentially neuronal diseases. Protein arginine methyltransferases (PRMTs) are a protein family that is highly conserved and can even be found in yeast (2). There are now 4 types of PRMTs known and arginine residues can be mono-methylated on the terminal nitrogen (by types, I, II and III) or on an internal nitrogen (by type IV). Arginine residues can further be modified by type I PRMTs resulting in asymmetric dimethylation of the terminal nitrogen, while type II PRMTs result in symmetric dimethylation of the terminal nitrogens. This field of research is fast moving and new findings about the mechanism and importance of protein arginine methylation are discovered and published every month. My lab has started to study protein arginine methylation initially in the HIV virus (3, 4) and work continues to clarify the role of protein arginine methylation of 2 HIV proteins. In addition, we have obtained preliminary data suggesting that arginine methylation may be important in the ageing process and may overlap with traditional Chinese herbal medicines used as anti-ageing compounds. Further, the work of one of my PhD students in 2011 has identified neuronal proteins that are methylated. We are in the process of studying the importance and role of protein arginine methylation in neurons and neuronal diseases as well as in other diseases including hepatitis, liver diseases, and cancer. Other areas of interest include studying the role of protein arginine methylation in cyanobacteria, bacteria and other microorganisms (collaborative projects with Dr Michelle Moffitt, Dr Oliver Morton, and Dr Colin Stack), in plants and mycorrhizal fungi (in collaboration with Dr Jonathan Plett at the HIE) and in ion channel forming proteins. Honours projects are available for each of the aims of the overall focus to elucidate the molecular mechanism of protein arginine methylation as listed below. Aim of Study: The major aim of the work conducted in my laboratory is to better understand protein arginine methylation and its importance in cellular pathways and disease in order to identify potential future drug targets to combat a variety of diseases. The specific aims and individual projects include: 1. Role of protein methylation in neurons and neuronal disease 2. Role of protein methylation in liver disease 3. Role of protein methylation in the regulation of cell cycle and cancer (in collaboration with Dr Qihan Dong) 4. Role of protein methylation in mycorrhizal fungi (in collaboration with Dr Jonathan Plett, HIE, Hawkesbury) 5. Role of protein methylation in microorganisms including cyanobacteria (co-supervised project with supervisor Dr Michelle Moffitt) 6. Role of protein methylation in ion channel forming proteins 7. Role of protein methylation in nuclear transport 8. Role of protein methylation in viral diseases including HIV, HCV, HBV 9. Role of protein methylation in ageing 10. Role of AdOx in protein and DNA methylation (in collaboration with Dr Patrice Castignolles, Parramatta) Methods: The major methods and techniques employed include, cell and tissue culture techniques (bacteria, yeast, eukaryotic cells), transformation, transfection, plasmid DNA preparations and purifications, PCR, site-directed mutagenesis, SDSPAGE, agarose gels, Western Blotting, immunoprecipitation, FACS studies, fluorescent confocal microscopy, and potentially some advanced microscopy techniques (FRET) ; 2D gels and mass spectrometry. Reagents and infrastructure as well as expertise with techniques is available in the Piller laboratory and from national and 306 international collaborators (including Prof Muench at SoM, Ass/Prof Roslyn London at UWA, Dr Michelle Moffitt, Dr Colin Stack, Dr Oliver Morton, Dr Patrice Castignolles, Dr Qihan Dong; SSH; Dr Jonathan Plett; HIE). Ethics Application Requirements: Most experiments are performed in cell lines and ethics approval for mouse work of primary cultured neurons is current and valid until end of 2015. Key References: 1) Paik et al. 2007 Trends in Biochemical Sciences 32(2):146-152; 2) Bedford and Clarke 2009 Molecular Cell 33: 1-13; 3) Willemsen et al. 2006 Retrovirology 3:92; 4) Mirto & Piller 2010 Future Medicine - HIV Therapy 4(1): 65. 307 Title of Project: Neuroplasticity, pain and movement (FOR Code/s): 110317; 110321; 110603; 110903 Supervisor: Professor Lucy Chipchase Contact: [email protected] (Phone 4620 3758) Co-supervisor: Contact: Location of Project: BRAiN-Laboratory, School of Science and Health, Campbelltown Campus Project Background The Brain Rehabilitation and Neuroplasticity Unit (BRAiN-U) aims to answer key basic science and clinical questions in the field of neuroplasticity, pain and motor learning. In addition, we aim to develop new brain-based treatments for neurological and musculoskeletal disorders. I am particularly interested, and currently conducting research, in a range of common clinical conditions including acute and chronic pain, anterior knee pain, knee osteoarthritis, and tennis elbow. I am also interested in how brain stimulation and therapeutic techniques can be used to enhance skill acquisition in sport (e.g. golf) and after injury. I have a range of projects available and am also open to discussing your ideas and suggestions for research in this field. Aim of Study: My research priorities are: 9. To understand the way the healthy human brain can change and adapt throughout life through investigation of neuroplastic mechanisms. 10. To understand how neuroplasticity is altered in musculoskeletal (chronic low back pain, osteoarthritis, tennis elbow) disorders. 11. To develop and test new and existing therapies that drive beneficial brain plasticity to alleviate pain and improve function in musculoskeletal disorders 12. To enhance learning in the healthy brain, learning of sports specific skills, re-learning of skills that have been lost through illness or injury, using non-invasive brain stimulation and other therapeutic techniques. Methods: The BRAiN-U laboratory is fully functional with two transcranial magnetic stimulation units, EMG, a neuronavigation system, transcranial direct current, acute pain models, motor learning tasks and quantitative sensory testing units. The methods would be selected based on each project. I have supervised over 20 Honours students, all of whom have achieved first class Honours. Six of these have progressed to PhDs being competitive for scholarships. Currently, our laboratory has a number of Honours and PhD students so you will work in a very engaging environment and have opportunities to gain skills and knowledge in the measurement and analysis of brain plasticity data and other specific measurement tools as well as working and collaborating with a number of research higher degree students and academics. I have a very collegial approach to mentoring and supporting beginning researchers. I aim to ensure that the work you conduct will be presented at conferences and be of a standard to submit for publication. My projects will suit students from a health science program (e.g. physiotherapy, exercise science, medicine) or a biomedical science with a strong drive to succeed and to learn from leaders in the field. Ethics Application Requirements: I have program ethics (#H10184) that covers a wide variety of projects. Amendments for individual projects would need to be sought. Key References: 308 15. 16. 17. 18. 19. 20. 21. Chipchase LS, Schabrun SM and Hodges PW (2011): Corticospinal excitability is dependent on the parameters of peripheral electrical stimulation: a preliminary study. Archives of Physical Medicine and Rehabilitation 92 (9): 1423-1430 [IF 2.284, 10/62 Rehabilitation journals] Chipchase LS, Schabrun SM and Hodges PW (2011): Peripheral electrical stimulation to induce cortical plasticity: a systematic review of stimulus parameters. Invited Review. Clinical Neurophysiology 122: 456-463 [IF 3.406, 46/192 of clinical neurology journals] Schabrun SM and Chipchase LS (2012): Priming the brain to learn: the future of therapy? Manual Therapy 17: 184-186. [IF 1.885, 18/62 Rehabilitation journals) Andrews R, Schabrun SM, Ridding MC, Galea M, Hodges PW and Chipchase LS (2013): Motor electrical stimulation and corticospinal excitability: the effect of application time. Journal of Neuroengineering and Rehabilitation 10: 51 (IF 2.57; 7/63 Rehabilitation journals; 22/79 Biomedical Engineering journals) Schabrun SM, Ridding MR and Chipchase LS (2013): An update on brain plasticity for physical therapists. Physiotherapy Practice and Research 34: 1-8. Adam K, Peters S and Chipchase L (2013): Knowledge, skills and professional behaviours required by occupational therapist and physiotherapist beginning practitioners in work-related practice: a systematic review. Aust J Occ Ther 60: 76-84 [IF 0.677] Chipchase LS, Schabrun SM, Cohen L, Hodges PW, Ridding MC, Rothwell J, Taylor J and Ziemann U (2012): A checklist for assessing the methodological quality of studies using transcranial magnetic stimulation to study the motor system: an international consensus study. Clinical Neurophysiology 123 (9): 1698-1704. [IF 3.406, 46/192 of clinical neurology journals] 309 Title of Project: The effect of chronic electrical stimulation on neuritogenesis. (FOR Code/s): 1109 Neurosciences 1103 Clinical sciences 060199 Biochemistry and Cell Biology not elsewhere classified 920107 Hearing, Vision, Speech and their disorders Supervisor: Dr Cherylea Browne Contact: 4620 3491 - [email protected] Co-supervisor: Dr Jennie Cederholm Contact: [email protected] Location of Project: Translational Neuroscience Facility, the University of New South Wales, and UWS Campbelltown. Project Background The events involved in transmitting sound information are crucial for us to perceive our surrounding environments. Unfortunately, there is a large population of people that suffer from hearing-related disorders, severe hearing loss or were born deaf [1]. The cochlear implant has been designed to stimulate the auditory neurons with electrical energy. The cochlear implant apparatus includes an external receiver, which receives sound information and transmits it to an external processor. The external processor transmits the electrical energy to the cochlear implant array which is positioned inside the cochlea. The signal is transmitted through the electrodes which stimulated the adjacent spiral ganglion neurons. The main issue that arises with cochlear implants is the poor electro-neural interface [2, 3]. The spiral ganglion neurites tend not to grow towards or connect to the implant array. However, it has been shown that spiral ganglion neurites can be encouraged to regenerate and grow in response to molecular therapy (e.g. neurotrophins) [4]. In addition to the efficacy of neurotrophins in restoring cochlear nerve vitality [5, 6], it is evident from several studies that electrical stimulation inherent to the cochlear implant can sustain the spiral ganglion neurons in the absence of neurotrophins [7]. Aim of Study: To determine the effect of chronic electrical stimulation on nerve cell outgrowth (neuritogenesis). Methods: The effect of chronic electrical stimulation on neuritogenesis will be assessed using an in vitro mouse spiral ganglion explant culture system we have developed at the University of New South Wales, Australia, which provides defined charge-balanced pulsed electric fields across the spiral ganglion cells (which is termed an “explant”). Spiral ganglion explants will be collected from young mice cochleae and cultured for two days in a mixture of growth factors. During this time the explant will be chronically stimulated with varying electric currents. Explants will then be processed for immunohistochemistry and will be analysed using a confocal microscope for growth and neurite extension in response to chronic stimulation. Ethics Application Requirements: Animal Ethics Approval applications will be made to the UNSW and UWS Animal Ethics Committees. Key References: 1. Mathers, C., Smith, A., & Concha, M. (2000). Global burden of hearing loss in the year 2000. Global burden of Disease, 18, 1-30. 2. Long, C. J., Holden, T. A., McClelland, G. H., Parkinson, W. S., Shelton, C., Kelsall, D. C., & Smith, Z. M. (2014). Examining the Electro-Neural Interface of Cochlear Implant Users Using Psychophysics, CT Scans, and Speech Understanding. Journal of the Association for Research in Otolaryngology, 1-12. 3. Bierer, J. A., Faulkner, K. F., & Tremblay, K. L. (2011). Identifying cochlear implant channels with poor electrodeneuron interface: electrically-evoked auditory brainstem responses measured with the partial tripolar configuration. Ear and hearing, 32(4), 436. 4. J. L. Pinyon, S. F. Tadros, K. E. Froud, A. C. Y. Wong, I. T. Tompson, E. N. Crawford, M. Ko, R. Morris, M. Klugmann, G. D. Housley, Close-field electroporation gene delivery using the cochlear implant electrode array enhances the bionic ear. Sci. Transl. Med. 6, 233ra54 (2014). 5. Wise, A.K., et al., Effects of localized neurotrophin gene expression on spiral ganglion neuron resprouting in the deafened cochlea. Mol Ther, 2010. 18(6): p. 1111-22. 6. Yu, Q., et al., Protection of spiral ganglion neurons from degeneration using small-molecule TrkB receptor agonists. J Neurosci, 2013. 33(32): p. 13042-52. 7. Leake, P.A., G.T. Hradek, and R.L. Snyder, Chronic electrical stimulation by a cochlear implant promotes survival of spiral ganglion neurons after neonatal deafness. J Comp Neurol, 1999. 412(4): p. 543-62. 310 Oncology & Carcinogensis 311 Field of Research: Title of Project: 0204 1103 1112 0306 MRI-based Electron Density Mapping for Radiotherapy Treatment Planning Supervisor: Prof William S Price Email: Co-supervisor: Dr Stephen Bosi (UNE) Email: [email protected] Telephone: 4620 3336 Telephone: Other members of the Nanoscale Research Group Campus project is offered and conducted: Campbelltown Background (max 500 words) Radiation therapy is a recommended treatment for approximately half of cancer cases [Delaney et al 2005]. Accurate planning of radiation dose requires both a picture of a patient's tissues and a map of the "electron density" of these tissues, currently obtained using CT (or "CAT") scans which use ionising radiation. At present an electron density (ED) map derived from a CT of the patient is the minimum requirement for treatment planning (TP) for external beam radiotherapy. Magnetic resonance imaging (MRI) scans actually provide a clearer tissue image than CT scans (and without using ionising radiation), but traditional medical MRI methods cannot provide a density map – at least not at the present time. Development of a new method which allows MRI to be used to measure tissue composition AND density would eliminate the extra radiation dose of a CT scan and streamline treatment planning. (Would suit students interested in Biology/Chemistry/Medical Physics/NMR) Aim of Study: The aim is to develop a method allowing MRI scanners to provide a tissue density map which is required for accurate radiation dose planning for radiation therapy. Methods: MRI Experiments + Analysis Ethics Application Requirements: Not Applicable Key References: 18. Delaney G., Jacob S., Featherstone C. et al. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer 104 1129-1137 (2005). 19. Khan F.M. "The Physics of Radiation Therapy" - 3rd ed., Lippincott & Wilkins. Philadelphia USA, 2003. 20. Wu Y., Reese T.G., Cao H., et al. Bone Mineral Imaged In Vivo by 31P Solid State MRI of Human Wrists J. Magn. Reson. Imaging. 34, 623–633 (2011). This is just one example of an Honours Project available in the Nanoscale Research Group (www.uws.edu.au/nanoscale). Many other projects are available (or can be developed) please consult with any member of the Nanoscale Group (Prof. William S. Price, Prof. Janice Aldrich-Wright, A/Prof. Gary Dennis, Dr Tim Stait-Gardner, Dr Bahman Ghadirian, Prof. Annemarie Hennessy, Prof. Andrew Shalliker, Dr Allan Torres, Dr Gang Zheng, Dr Scott Willis). 312 Title of Project: To investigate the role of SMG1 in innate immune signalling. (FOR Code/s): 060111 Signal Transduction, 110707 Innate Immunity, 111201 Cancer Cell Biology, 111206 Haematological Tumours Supervisor: Dr Tara Roberts Contact: [email protected] Co-supervisor: Dr Uda Ho (TBC) Contact: (02) 87389020 Location of Project: The Ingham Institute for Applied Medical Research. Project Background SMG1 is a member of the PI-3 kinase like kinase (PIKK) family of proteins which include ATM, DNA-PK and mTOR. Members of this family have well-characterised roles in responses to cellular stress including DNA damage and nutrient deprivation. We recently described a novel role for SMG1 as a tumour suppressor. Decreased SMG1 protein expression led to increased development of cancer, particularly lymphomas and lung adenocarcinomas. SMG1 loss also increased basal inflammation and oxidative damage to tissues prior to tumour development. These data suggest that SMG1 may contribute to cancer development, at least partially, by promoting inflammation. Aim of Study: To understand how loss of SMG1 alters innate immune responses. This study will focus on determining if and how SMG1 loss alters toll-like receptor mediated responses and inflammasome activation. Methods: This project will utilise a range of methods including mammalian cell tissue culture, siRNA knockdown, cellular activation assays (ELISA, Flow cytometry), cell signalling analysis (western blotting, immunofluorescence) as well as isolation and analysis of cells from genetically modified mice. Ethics Application Requirements: This project already has animal ethics and OGTR approval. Key References: Background to project: Roberts TL, Ho U, et al. (2013) Smg1 haploinsufficiency predisposes to tumor formation and inflammation. Proc Natl Acad Sci U S A 110(4):E285-294. Hanahan D & Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646-674. Li N, Grivennikov SI, et al. (2011) The unholy trinity: inflammation, cytokines, and STAT3 shape the cancer microenvironment. Cancer Cell 19(4):429-431. Indication of techniques: Roberts TL, Dunn JA, et al. (2011) The immunostimulatory activity of phosphorothioate CpG oligonucleotides is affected by distal sequence changes. Mol Immunol 48(8):1027-1034. Roberts TL, Idris A, et al. (2009) HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science 323(5917):1057-1060. 313 Paediatrics & Reproductive Medicine 314 Title of Project: Children’s footwear knowledge and consumer influence: a qualitative study (FOR Code/s): 11 Medical and Health Sciences, 111403 Paediatrics, 730299 Public Health Supervisor: Dr Stef Penkala Contact: Ph 4620 3742, email [email protected] Location of Project: Campbelltown Project Background Foot problems related to shoes are common among children in Australia (1). In a survey of 272 parents of children aged 4 to 12 years, 28% identified foot problems occurring within a one- month period, with almost half attributing foot problems to footwear (1). While parents prioritise comfort and fit of children’s shoes, most parents (94%) report reliance on their child’s assessment of comfort. However, parents (27%) report children are more concerned with shoe appearance than comfort (2). While children are reported to influence 28% of shoe choices (2), they do not necessarily have the footwear knowledge or consumer integrity to effectively facilitate informed decisions. Selective marketing targets children, influencing individual and family spending by $1.18 trillion per year (3). While children are increasingly consumer-aware and brand conscious this sophistication is age specific. Children as young as 3 and 4 years can recognise brand names. However, it is not until 6 to 12 years that cognitive and social values of brands become more evident. Footwear choices based on social status, prestige, group affiliation and self-image rather than affordability, function and fit raise concerns for foot health and physical activity participation(1). Young children are generally reliant consumers, depending on guidance from parents. However, from 8 years of age, children exert greater consumer independence (2,5,6) influencing expensive sports shoe purchases (2). Parents require evidence based knowledge and strategies to facilitate children’s footwear choices. Understanding children’s consumer identity and footwear knowledge is needed to counter less than optimal footwear purchases which may impact of foot health and activity. Aim of Study: The aim of this study is to explore children’s footwear knowledge and influences on footwear choices. Methods: This study undertakes a qualitative research approach. Focus groups of about 4 to 8 children will be employed for data collection. Focus group discussions with be audio recorded and transcribed verbatim. Qualitative thematic content analysis will be used to identify common themes and report the data. Ethics Application Requirements: NEAF Required Key References: 1. Penkala S, Harris L, Hunt A and Naughton G (2010) Foot complaints of children aged four to twelve years, sex differences and activity – a cross-sectional survey of parents. Journal of Science and Medicine in Sport 12(2): 107 2. Penkala, S, Harris, L, Hunt, A & Naughton, G (2011) 'Children’s shoe styles and parent decisions to fit shoes with store staff assistance', Journal of Foot and Ankle Research 4(1):35 3. Lindstrom, M. (2004). Branding is no longer child's play. Journal of Consumer Marketing, 21(3), 175-182. 4. Achenreiner, G. B., & John, D. R. (2003). The meaning of brand names to children: A developmental investigation. Journal of Consumer Psychology, 13(3), 205-219. 5. Ross, J., & Harradine, R. (2004). I'm not wearing! Branding and young children. Journal of fashion marketing and management, 8(1), 11-26. 6. Ishida, M. D. (1980). Mother-child management of interactions at choice points. Journal for the Study of Interpersonal Processes, 43(1), 71-77. 315 Title of Project: Idiopathic toe walking: Can a novel exercise program to address sensory and motor skill challenges be beneficial? (FOR Code/s): 11 Medical and Health Sciences, 111403 Paediatrics, 110603 Motor Control, 730299 Public Health Supervisor: Dr Stef Penkala Contact: Ph 4620 3742, email [email protected] Location of Project: Campbelltown Project Background Gait anomalies in early childhood are a concern for parents and common source of health professional referral. Toewalking defined as the absence of heel contact can be a normal gait variant until 3 years of age (1). However, aetiology including disease, neurological influences and trauma, require screening (1). In the absence of medical conditions, persistent toe walking beyond 3 years of age is considered idiopathic, effecting around 12 % of the paediatric population (2). While idiopathic toe walking (ITW) has no medical cause, links to speech, language (3) and sensory processing (4) difficulties associated with vestibular and sensory anomalies are reported. In a case control study (n= 60) children with ITW demonstrated hypersensitivity of vibration perception threshold (p<0.001), lower Standing Walking Balance subtests (p=0.47) and motor proficiency (p=0.001), compared to norms (4). A range of treatments have been advocated in the management of toe walking including, surgery, casting, stretching, botulinum toxin type A injections and orthotics, particularly in the presence of tight calf structures. However, toe walking can persist beyond the resolution of tight calf structures (5). Interventions beyond the ‘structural’ framework require consideration. Given the links between proficient sensory and motor control with physical activity participation, ITW interventions that can address sensory and motor skill challenges may be beneficial. This study will investigate a novel exercise program to address sensory and motor skill challenges in children with ITW. Aim of Study: The aim of the study of the study is to investigate the benefits of a novel exercise program to address sensory and motor skill challenges in children with ITW. Methods: This study will use a case-control design. Children with ITW will be recruited and screened with the Toe Walking Tool (6) for inclusion. Children will be asked to participate in 8 to 12 exercise sessions challenging sensory and motor input. Pre and post measures will include vibration perception threshold, Standing Walking Balance subtests and motor proficiency. Ethics Application Requirements: NEAF Required Key References: 7. Williams CM, Timey P and Rawicki B Have We Progressed in our Knowledge of the Causality and Treatment of this Gait Type? JAPMA 2014, 104:3 253-61 8. Fox A, Deakin S, Pettigrew G, Paton R: Serial casting in the treatment of idiopathic toe-walkers and review of the literature. Acta Orthop Belg 2006, 72:722-730. 9. Shulman LH, Sala DA, Chu MLY, McCaul PR, Sandler BJ. Developmental implications of idiopathic toe walking. J Pediatr. 1997, 130:541-546. 10. Williams CM, Tinley P, Curtin M, Wakefield S and Nielsen S. Is Idiopathic Toe Walking Really Idiopathic? The Motor Skills and Sensory Processing Abilities Associated With Idiopathic Toe Walking Gait. J Child Neurol 2014, 29: 71 11. Eastwood DM, Menelaus D, Dickens RV, Broughton NS, Cole WG. Idiopathic toe-walking: does treatment alter the natural history? J Pediatr Orthop B. 2000, 9:47-49. 12. Williams CM, Tinley P and Curtin M The Toe Walking Tool: A novel method for assessing idiopathic toe walking children. Gait & Posture 2010, 32: 508–511 316 Medical Physiology 317 Title of Project: The role of the PID domain of Brd4 in the interaction with the P-TEFb transcriptional complex (FOR Code/s): 1116 (Medical Physiology), 0601 (Biochemistry and Molecular Biology) Supervisor: Dr Roland Gamsjaeger Contact: [email protected] Co-supervisor: Dr Liza Cubeddu Contact: [email protected] Location of Project: Campbelltown Project Background It is well established that chromatin, which packages eukaryotic DNA, plays an important role in transcriptional regulation. Recently, post-translational modifications on histone tails have been directly implicated with gene activation or repression. Although the role of bromodomains as effective ‘readers’ of acetylation marks on histones has been established over the last 5–10 years, accumulating evidence points to a scenario in which these proteins also have a role in other essential cellular processes. To date, the most widely studied is the involvement of the BET-family bromodomain protein Brd4 in the recruitment of P-TEFb, which regulates gene expression by enabling the elongation of transcription. The related BET bromodomain protein Brd3 has also been identified as a binding partner of P-TEFb, however, comparatively little is known about the molecular details of this interaction. Recent studies have shown that displacement of Brd4 from acetylated histones on chromatin using small molecule inhibitors is a promising new therapy for effective treatment of MLL-fusion leukaemia and pharmaceutical companies are currently aggressively pursuing Brd4 inhibitors. However, the same inhibitors that abrogate Brd4 binding show equal efficacy against Brd3. If such inhibitors are to be clinically useful, understanding, at a fundamental level, the role of Brd3 is absolutely critical for targeting specific disease states and preventing undesired off-target side effects. Aim of Study: Determine the role of the PID domain of Brd4 in the interaction with the P-TEFb complex using biophysical and structural approaches. Methods: Expression of the PID domain (Protein Interaction domain) of Brd4. Testing the interaction of the PID domain with CycT1 and Cdk9, both components of the P-TEFb complex. Structural characterisation of the PID domain and comparison with Brd3. Ethics Application Requirements: NA Key References: Dawson, M.A., Prinjha, R.K., Dittmann, A., Giotopoulos, G., Bantscheff, M., Chan, W.I., Robson, S.C., Chung, C.W., Hopf, C., Savitski, M.M. et al. (2011) Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature, 478, 529-533 Gamsjaeger, R., Webb, S.R., Lamonica, J.M., Billin, A., Blobel, G.A. and Mackay, J.P. (2011) Structural basis and specificity of acetylated transcription factor GATA1 recognition by BET family bromodomain protein Brd3. Mol Cell Biol, 31, 2632-2640 Zuber, J., Shi, J., Wang, E., Rappaport, A.R., Herrmann, H., Sison, E.A., Magoon, D., Qi, J., Blatt, K., Wunderlich, M. et al. (2011) RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature, 478, 524-528 318 Public Health & Health Services 319 Title of Project: ACTIVE RECOVERY - FITNESS & SPORTS PROGRAM FOR YOUTH WITH SERIOUS MENTAL ILLNESS IN WESTERN SYDNEY (FOR Code/s): 110699, 111714 Supervisor: A/ Prof Merom D. Contact: [email protected] Co-supervisors: Andrew Bennie Contact: [email protected] Location of Project: UWS Penrith and Campbelltown campuses Project Background People who have serious mental illness, including major depression, schizophrenia, and bipolar disorder, experience significant psychological, social, and cognitive disability and poor physical health due to the side effects of anti-psychotic drugs, which associate with large weight gain, metabolic disorder and risk of diabetes. Physical activity can improve these conditions, but the negative symptoms of their illness (e.g. low motivation, low self-esteem) highlight the challenge of maintaining an active lifestyle without a strong motivator. A review of the benefits of sport participation in adolescents underscore the psychological benefits of team sport, including reduced social isolation later in life, improved self-esteem, life satisfaction, reduced depression and anxiety symptoms and hopelessness and suicidality. These benefits were attributed to positive experiences from skills development, peer support and reduced body dissatisfaction. Aim of Study: 1) to evaluate the mental health benefits of fitness & sports program delivered to youth with serious mental health illness 2) to assess its impact on daily physical activity of youth with serious mental illness 3) to evaluate the effect of the program on social closeness and skills 4) to conduct qualitative evaluation of program implementation and satisfaction to be submitted to the organisations involved. Methods: This is a pilot study (pre/post evaluation design) with an aim to support a bigger NHMRC partnership grant. As a pilot it is a perfect topic for Honours research project. The program will be delivered to 10 young males and females with mental illness. Participants will be provided with active wear and accessories and transport to the venue by RichmondPRA, one of Australia’s most experienced non-profit mental health organisation. The project will engage youth with a serious mental illness in physical activities with emphasis on enjoyment, social interaction, fitness and continuity. The program will be delivered three times a week for 1.5 hours each session over 16 weeks. People with mental illness start at a very low level of fitness and may withdraw due to unpleasent sensation with increased efforts. The Active Recovery program will therefore be gradual. The idea is to devote up to 2 days to bootcamp activities with fitness assessments conducted for each participant pre, during & post program. The third day of the week will be devoted to sports such as mixed oztag, handball, basketball, soccer and volleyball. Each session will start with drills to improve game-specific skills in pairs or triplets. In the next hour the game is played and referees are rotates from the group. During the activity participants will wear motion sensors to provide immediate feedback on the duration at each intensity level and number of steps taken. The outcomes of this program will include clinically relevant measures of mental health, increases in daily physical activity, social interaction as well as barriers for program implementations and participants’ satisfaction and feedback. Participants will be transported to UWS sports ground. The project has funding to pay for the instructor time. This topic can involve two honours students given the quantitative and qualitative scope of this pilot and the social aspect. Data collection, analysis will be conducted by the research students with guidance from supervisor. Successful students will be able to start a lifelong career in the area of mental illness and sports participation working with governmental and non-governmental agencies. Ethics Application Requirements: yes, need to be submitted before the end of the year so approval is ready in January. Key References: 5. Eime RM et al A systematic review of the psychological and social benefits of participation in sport for children and adolescents: informing development of a conceptual model of health through sport. International Journal of Behavioral Nutrition and Physical Activity 2013, 10:98http://www.ijbnpa.org/content/10/1/98 6. Biddle S & Asare. Physical activity and mental health in children and adolescents: review of reviews.vBr J Sports Med 2011;45:886–895. doi:10.1136/886 bjsports-2011-090185 7. Masi, C. M., Chen, H., Hawkley, L. C., & Cacioppo, J. T. (2011). A meta-analysisof interventions to reduce loneliness. Personality and Social Psychology Review,15(3), 219–266 320 Title of Project: How much does where children live influence their mental and physical health? (FOR Code/s): 1117 Public Health and Health Services Supervisor: Dr Thomas Astell-Burt Contact: [email protected] Co-supervisor: Dr Jill Hnatiuk Contact: TBC Location of Project: Campbelltown as main campus, though working on other campuses is negotiable Project Background: Where children live can shape what they can or cannot do. What is less known is what types of neighbourhood environment promote better mental and physical health in children. Knowing this will help planners build healthier, liveable communities for future generations of Australian children. Aim of Study: This study will enhance understandings on what types of neighbourhood promote child health. Methods: Data from 10,000 children living all over Australia will be analysed. Ethics Application Requirements: Use of data will require low-risk ethical approval. Key References: Kawachi, I. & Berkman, L.F. 2003. Neighborhoods and health, Oxford University Press, USA. 321 Title of Project: Community parks for better health: what types of park are attractive and for whom? (FOR Code/s): 1117 Public Health and Health Services Supervisor: Dr Thomas Astell-Burt Contact: [email protected] Co-supervisor: TBA Contact: Location of Project: Campbelltown as main campus, though working on other campuses is negotiable Project Background: Research suggests that community parks are potentially important promoters of health. Less is known on who uses parks and what features of those parks are attractive for promoting health. Aim of Study: This study will enhance understandings of who uses parks and what features of those parks are attractive for promoting health in three main age groups: (i) young children; (ii) adults; (iii) pensioners. Methods: Data will be collected via participant observation in a range of parks in Sydney using a validated instrument. Additional evidence will be collected using a field diary and photography. Ethics Application Requirements: Use of data collection instruments will require ethical approval. Key References: Astell-Burt, T., Mitchell, R. & Hartig, T. 2014. The association between green space and mental health varies across the lifecourse. A longitudinal study. Journal of Epidemiology & Community Health, 68, 578-583. Astell-Burt, T., Feng, X., Mavoa, S., Badland, H. M. & Giles-Corti, B. 2014. Do low-income neighbourhoods have the least green space? A cross-sectional study of Australia’s most populous cities. BMC Public Health, 14, 292. Astell-Burt, T., Feng, X., & Kolt, G.S. 2014. Greener neighborhoods, slimmer people? Evidence from 246,920 Australians. International Journal of Obesity, 38, 156-159 322 Title of Project: Do food deserts exist in Western Sydney and, if so, what do they look like? (FOR Code/s): 1117 Public Health and Health Services Supervisor: Dr Thomas Astell-Burt Contact: [email protected] Co-supervisor: TBA Contact: Location of Project: Campbelltown as main campus, though working on other campuses is negotiable Project Background: Diets high in fat and sugar are important determinants of obesity and poor health, both of which are common in Western Sydney communities. Food deserts are neighbourhoods where access to high fat, high sugar food is easy, but healthier food options are unavailable. Are there food deserts in Western Sydney? Aim of Study: This study will examine evidence to understand whether food deserts exist in Western Sydney. Methods: Data will be collected via participant observation and semi-structured interviews. Additional evidence will be collected using a field diary and photography. Ethics Application Requirements: Use of data collection instruments will require ethical approval. Key References: Kawachi, I. & Berkman, L.F. 2003. Neighborhoods and health, Oxford University Press, USA. 323 Title of Project: New supermarket, better health? (FOR Code/s): 1117 Public Health and Health Services Supervisor: Dr Thomas Astell-Burt Contact: [email protected] Co-supervisor: TBA Contact: TBA Location of Project: Campbelltown as main campus, though working on other campuses is negotiable Project Background: Many communities in Western Sydney live far from a supermarket, which leads to dependency upon cars for purchasing food. Little is known, however, on what happens when a new supermarket opens. Do local residents change what food they purchase and eat? Are they less car dependent? Aim of Study: This study will improve knowledge on the role of supermarkets in changing people’s diets. Methods: Data will be collected via semi-structured interviews and a short survey. Additional evidence will be collected using a field diary and photography. Ethics Application Requirements: Use of data collection instruments will require ethical approval. Key References: Kawachi, I. & Berkman, L.F. 2003. Neighborhoods and health, Oxford University Press, USA. 324 Title of Project: What impacts will Western Sydney’s south west rail link have on the local community? (FOR Code/s): 1117 Public Health and Health Services Supervisor: Dr Thomas Astell-Burt Contact: [email protected] Co-supervisor: TBA Contact: Location of Project: Campbelltown as main campus, though working on other campuses is negotiable Project Background: Car dependency is common in Western Sydney. This is implicated in rising levels of obesity. In 2015, a new rail-link will open in area of south west Sydney, providing services to people who were previously car dependent. Little is known as to what impact this will have on the local community. Aim of Study: This study will enhance understandings of how investments in public transport infrastructure influence local communities in terms of health, commuting and satisfaction with their neighbourhood. Methods: Data will be collected via participant observation, semi-structured interviews and a short survey using a validated instrument. Additional evidence will be collected using a field diary and photography. Ethics Application Requirements: Use of data collection instruments will require ethical approval. Key References: Kawachi, I. & Berkman, L.F. 2003. Neighborhoods and health, Oxford University Press, USA. 325 Title of Project: Children’s footwear knowledge and consumer influence: a qualitative study (FOR Code/s): 11 Medical and Health Sciences, 111403 Paediatrics, 730299 Public Health Supervisor: Dr Stef Penkala Contact: Ph 4620 3742, email [email protected] Location of Project: Campbelltown Project Background Foot problems related to shoes are common among children in Australia (1). In a survey of 272 parents of children aged 4 to 12 years, 28% identified foot problems occurring within a one- month period, with almost half attributing foot problems to footwear (1). While parents prioritise comfort and fit of children’s shoes, most parents (94%) report reliance on their child’s assessment of comfort. However, parents (27%) report children are more concerned with shoe appearance than comfort (2). While children are reported to influence 28% of shoe choices (2), they do not necessarily have the footwear knowledge or consumer integrity to effectively facilitate informed decisions. Selective marketing targets children, influencing individual and family spending by $1.18 trillion per year (3). While children are increasingly consumer-aware and brand conscious this sophistication is age specific. Children as young as 3 and 4 years can recognise brand names. However, it is not until 6 to 12 years that cognitive and social values of brands become more evident. Footwear choices based on social status, prestige, group affiliation and self-image rather than affordability, function and fit raise concerns for foot health and physical activity participation(1). Young children are generally reliant consumers, depending on guidance from parents. However, from 8 years of age, children exert greater consumer independence (2,5,6) influencing expensive sports shoe purchases (2). Parents require evidence based knowledge and strategies to facilitate children’s footwear choices. Understanding children’s consumer identity and footwear knowledge is needed to counter less than optimal footwear purchases which may impact of foot health and activity. Aim of Study: The aim of this study is to explore children’s footwear knowledge and influences on footwear choices. Methods: This study undertakes a qualitative research approach. Focus groups of about 4 to 8 children will be employed for data collection. Focus group discussions with be audio recorded and transcribed verbatim. Qualitative thematic content analysis will be used to identify common themes and report the data. Ethics Application Requirements: NEAF Required Key References: 7. Penkala S, Harris L, Hunt A and Naughton G (2010) Foot complaints of children aged four to twelve years, sex differences and activity – a cross-sectional survey of parents. Journal of Science and Medicine in Sport 12(2): 107 8. Penkala, S, Harris, L, Hunt, A & Naughton, G (2011) 'Children’s shoe styles and parent decisions to fit shoes with store staff assistance', Journal of Foot and Ankle Research 4(1):35 9. Lindstrom, M. (2004). Branding is no longer child's play. Journal of Consumer Marketing, 21(3), 175-182. 10. Achenreiner, G. B., & John, D. R. (2003). The meaning of brand names to children: A developmental investigation. Journal of Consumer Psychology, 13(3), 205-219. 11. Ross, J., & Harradine, R. (2004). I'm not wearing! Branding and young children. Journal of fashion marketing and management, 8(1), 11-26. 12. Ishida, M. D. (1980). Mother-child management of interactions at choice points. Journal for the Study of Interpersonal Processes, 43(1), 71-77. 326 Title of Project: Perceptions of older adults’ on participation in a social dancing program: determining the active and inactive ingredients of the program (FOR Code/s): 110699, 111714 Supervisor: A/ Prof Merom D. Contact: [email protected] Co-supervisors: Dr. Freya Macmillan Contact: [email protected] Location of Project: UWS Penrith and Campbelltown campuses Project Background As Australia confronts an unprecedented aging of the population, identifying effective strategies that address processes of aging and their adverse health outcomes have emerged as a major public health and economic challenge. Age-related physiological and cognitive declines are associated with declines in participation in physical activity. Dance is a complex sensorimotor rhythmic activity with additional mental and social components. The Dance Ageing Cognition and Economic (DAnCE) randomized controlled trial is an NHMRC funded research project aimed at testing the effect of a social dancing program on older adults’ falls and risk factors of falls. The trial was implemented within 23 retirement villages across the Greater Sydney area, and villages were randomized to an intervention or wait list control arm. The follow-up data finished in September, 2014, while control villages are still getting the dance program and will gradually finish their involvement in the trial until July 2015. This study is designed to gauge perceptions of older adults’ participation in two different dance-based programs: folk dance and ballroom dancing with a bigger trial that will test the efficacy of these programs on falls events, risk factors for falls and cost-effectiveness. Data from this project will inform health practitioners whether there is a potential to increase the proportion of inactive older adults who will take part in social dance as a lifelong solution to be active and if not why? The qualitative evaluation will identify issues related to program acceptability, difficulties, and maintenance. We will be able also to determine if social dancing is considered a fun activity that is suitably physically challenging and whether perceptions are different for novice versus experienced dance participants. Aim of Study: 1 )To learn how to conduct focus groups for the qualitative evaluation of health promotion programs 2)To engage and master the process of analyzing qualitative data 3)To gain experience in writing a qualitative paper Methods Participants in the intervention arm were invited to take part in focus groups discussion in their village. Dr. MacMillan, an expert in the area of qualitative evaluation of health promotion programs, and A/Pro Merom, the chief investigator of the project, have developed the semi-structured topic aid for the qualitative evaluation. The student is expected to review the literature on qualitative evaluation of dance based intervention, to conduct a few focus groups and to lead discussion, if confident, with the guidance of Dr MacMillan. In addition, the student will be expected to transcribe the recordings and to engage in analyzing the material under Dr. MacMillan’s guidance, to summarise he results and to contribute to paper writing. Ethics Application Requirements: No need to be submitted before the end of the year so approval is ready in January. Key References: 8. Merom et al Can social dancing prevent falls in older adults? A protocol of the Dance, Aging, Cognition, Economics (DAnCE) fall prevention randomised controlled trial 327 Title of Project: Investigating physical activity and health in culturally and linguistically diverse adults (FOR Code/s): 111706 Epidemiology Supervisor: Dr Emma George Contact: [email protected] Co-supervisor: Prof Gregory Kolt Contact: [email protected] Location of Project: Campbelltown or Penrith Note: Projects are available for a range of Honours students. Project Background The life expectancy of Australians has increased over recent decades, and is one of the highest in the world. This trend, paired with periods of low fertility, has resulted in a rapidly ageing Australian population, placing increasing demand on health and welfare services, health expenditure and the demand for health and aged care services. The 45 and Up Study (www.45andup.org.au) is the largest ongoing study of healthy ageing in the Southern Hemisphere. At baseline, data on a range of health, quality of life, and demographic variables were collected from 267,153 men and women aged 45 years and over, living in NSW. Follow-up data for approximately 27,000 participants are now available, providing the opportunity to examine prospective associations between lifestyle factors such as physical activity and sedentary time, and a range of health-related variables. Adults from culturally and linguistically diverse (CALD) groups experience a number of health disparities, including higher rates of chronic diseases in comparison to their Australian-born counterparts (Henderson, Kendall & See, 2011). Adults from CALD populations are also less likely to seek preventive health services, and are less likely to participate in regular physical activity – a lifestyle behaviour that is associated with positive health outcomes (Caperchione, Kolt & Mummery, 2009). Aim of Study: More than one Honours student can work in this area, and topics can be shaped to the expertise and interest of the students. Utilising baseline and follow-up data from the large-scale 45 and Up Study, the aim of this project is to examine the prospective associations between physical activity and/or sedentary time and a range of health-related variables in middle-aged and older adults from CALD populations. Students with an interest in the role physical activity plays in health and an interest in epidemiology will have the opportunity to select health outcomes of interest for examination. The findings from these projects will contribute to a growing body of evidence related to the health and wellbeing of Australian adults and will help inform the design of future health promotion initiatives and policies relevant to areas such as Greater Western Sydney with its culturally diverse population. Methods: Through this project, the Honours student/s will gain valuable skills in reviewing and critiquing literature, analysis of data, and interpreting and writing up the findings. It is anticipated that this work will lead to the publication of a scientific paper in a peer-reviewed journal. Opportunities will also exist for suitable students to progress into a PhD after completion of their Honours degree. Ethics Application Requirements: Only reciprocal ethics approval (at UWS) will be required for this project, as approval has already been obtained for the larger 45 and Up Study and related sub-studies. Key References: 45 and Up Study Collaborators. (2008). Cohort profile: The 45 and Up Study. International Journal of Epidemiology, 35(5), 941-947. doi: 10.1093/ije/dym184 Caperchione, C. M., Kolt, G. S., & Mummery, W. K. (2009). Physical activity in culturally and linguistically diverse migrant groups to Western Society. Sports Medicine, 39(3), 167-177. doi: 10.2165/00007256-20093903000001 George, E. S., Rosenkranz, R. R., & Kolt, G. S. (2013). Chronic disease and sitting time in middle-aged Australian males: Findings from the 45 and Up Study. International Journal of Behavioral Nutrition and Physical Activity, 10, 20. doi: 10.1186/1479-5868-10-20 Henderson, S., Kendall, E., & See, L. (2011). The effectiveness of culturally appropriate interventions to manage or prevent chronic disease in culturally and linguistically diverse communities: A systematic literature review. Health & Social Care in the Community, 19(3), 225-249. doi: 10.1111/j.1365-2524.2010.00972.x 328 Title of Project: A systematic review of health promotion initiatives in sporting clubs (FOR Code/s): 111712 Health Promotion Supervisor: Dr Emma George Contact: [email protected] Co-supervisor: Prof Gregory Kolt Contact: [email protected] Location of Project: Campbelltown or Penrith Project Background Sporting clubs provide an important setting for the promotion of healthy lifestyle behaviours, and have great potential to attract participants to engage in health promotion initiatives. In recent years, researchers have increasingly utilised the sporting club environment and have drawn upon the passion, loyalty, and validation associated with being a sports fan, for the promotion of healthy lifestyle behaviours (Gray et al., 2013; Pringle, 2009; Pringle et al., 2011). These innovative interventions that have been developed have the potential to engage hard-toreach population groups including middle-aged males, and individuals from low socioeconomic communities. Systematic reviews exploring health promotion policies in sporting clubs (Priest, Armstrong, Doyle & Waters, 2008) and interventions through sporting clubs to increase participation in sport (Priest, Armstrong, Doyle & Waters, 2008b) have been conducted, however there are currently no systematic reviews examining health promotion interventions run through sporting clubs. Aim of Study: The aim of this study is to systematically collate, evaluate and synthesise the results of health promotion interventions run through sporting clubs. The findings of this systematic review will help inform the design of future health promotion initiatives targeting hard-to-reach population groups. Methods: Through this project, the Honours student will gain valuable skills in searching, reviewing and critiquing literature, analysis of data, and interpreting and writing up the findings of a systematic review. It is anticipated that this work will lead to the publication of a scientific paper in a peer-reviewed journal. Opportunities will also exist for suitable students to progress into a PhD after completion of their Honours degree. Ethics Application Requirements: Ethics approval is not required for this study. Key References: Gray, C. M., Hunt, K., Mutrie, N., Anderson, A. S., Leishman, J., Dalgarno, L., & Wyke, S. (2013). Football Fans in Training: The development and optimization of an intervention delivered through professional sports clubs to help men lose weight, become more active and adopt healthier eating habits. BMC Public Health, 13(1), 232. doi: 10.1186/1471-2458-13-232 Priest, N., Armstrong, R., Doyle, J., & Waters, E. (2008). Policy interventions implemented through sporting organisations for promoting healthy behaviour change. Cochrane Database of Systematic Reviews, 3. doi: 10.1002/14651858.CD004809.pub3 Priest, N., Armstrong, R., Doyle, J., & Waters, E. (2008b). Interventions implemented through sporting organisations for increasing participation in sport. Cochrane Database of Systematic Reviews, 3. doi: 10.1002/14651858.CD004812.pub3 Pringle, A. (2009). The growing role of football as a vehicle for interventions in mental health care. Journal of Psychiatric and Mental Health Nursing, 16(6), 553-557. doi: 10.1111/j.1365-2850.2009.01417.x Pringle, A., Zwolinsky, S., Smith, A., Robertson, S., McKenna, J., & White, A. (2011). The pre-adoption demographic and health profiles of men participating in a programme of men’s health delivered in English Premier League football clubs. Public Health, 125(7), 411-416. doi: http://dx.doi.org/10.1016/j.puhe.2011.04.013 329 Title of Project: Predicting participation in the Healthy Environments and Active Living Study (HEALStudy) (FOR Code/s): 1106 (Human Movement and Sports Science); 1117 (Public Health and Health Services); Supervisor*: Dr Freya MacMillan Contact: [email protected] Supervisor*: Dr Thomas Astell-Burt Contact: [email protected] Location of Project: Campbelltown campus * Joint supervision – each contributing equally Project Background The Healthy Environments and Active Living Study (HEALStudy) is exploring how changes in built environment potentially influence community health in South West Sydney. Participants in the HEALStudy are being tracked over time, but some people will drop out over time due to various reasons (e.g. leaving the area). Meanwhile, other participants in the main survey may or may not choose to take part in sub-studies involving use of accelerometers. Continued participation and drop-out is, therefore, not random and this could have important implications for the results. Aim of Study: The aim of this study is to examine the factors which predict participation and drop-out in the HEALStudy and associated sub-studies. Methods: State-of-the-art techniques to resolve attrition and missing data in longitudinal studies will be reviewed in order to understand their cost-benefits. A selected set of those techniques will then be applied to data from the HEALStudy using relevant statistical models. Ethics Application Requirements: Ethical approval has already been granted for this study and data collection is underway. Key References: Tambs K, Ronning T, Prescott CA, Kendler KS, Reichborn-Kjennerud T, et al. (2009) The Norwegian Institute of Public Health twin study of mental health: examining recruitment and attrition bias. Twin Res Hum Genet 12: 158–168 STERNE, J. A., WHITE, I. R., CARLIN, J. B., SPRATT, M., ROYSTON, P., KENWARD, M. G., WOOD, A. M. & CARPENTER, J. R. 2009. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. Bmj, 338: b2393. 330 Title of Project: When do eating disorders start? How common are DSM-5 eating disorders? What are the sociodemographic correlates and health related burden of eating disorders in the community? (FOR Code/s):110319 Psychiatry 111714 Mental health Supervisor: Prof Hay Contact: [email protected] Co-supervisor: Dr Slewa-Younan Contact: [email protected] Location of Project: not locality dependant Project Background There is evidence that the distribution and determinants of eating disorders in the community is changing with increasing numbers of men and people from disadvantaged backgrounds with eating disorders. This project has potential for the student to also develop their own alternate or additional ideas and questions from previously collected data. Aim of Study: To investigate prevalence and sociodemographic determinants of eating disorders. Methods: A nested study within a large community survey conducted in 2014 with comparative data from 1995, 1998, 2005 and 2008/9 surveys in South Australia. Ethics Application Requirements: HREC is obtained. The student and the nested project will need to be added to current study investigators. Key References: Mitchison, D., Hay, P., Slewa-Younan, S., & Mond, J. (2012). Time trends in population prevalence of eating disorder behaviors and their relationship to quality of life. PloS one, 7(11), e48450. Mitchison D, Hay P, Slewa-Younan S, Mond J.The changing demographic profile of eating disorder behaviors in the community.BMC Public Health. 2014 Sep 11;14(1):943. 331 Title of Project: Health literacy of people with obesity and binge eating. (FOR Code/s):110319 Psychiatry 111714 Mental health Supervisor: Prof Hay Contact:[email protected] Co-supervisor: Dr Slewa-Younan Contact: [email protected] Location of Project: not locality dependant Project Background Binge eating disorders is common in people who are overweight but the problem is under-recognised and undertreated despite the availability of evidence based treatments. Poor health literacy likely contributes to this treatment gap. Aim of Study: To better understand putative reasons for the treatment gap in people with binge eating disorder and obesity. Methods: A nested study is being conducted within a randomised controlled trial for obesity where by health literacy in regards to both binge eating disorder and obesity is being assessed in 100 participants. Ethics Application Requirements: HREC is obtained. The student and the nested project will need to be added to current study investigators. Key References: Mond JM, Hay PJ, Rodgers B, Owen C. (2007). Health service utilization for eating disorders: Findings from a community‐based study. International Journal of Eating Disorders, 40(5), 399-408. Mond JM, Hay PJ. (2008). Public perceptions of binge eating and its treatment. International Journal of Eating Disorders, 41(5), 419-426. Jorm, A F., et al. "Research on mental health literacy: what we know and what we still need to know." Australian and New Zealand Journal of Psychiatry 40.1 (2006): 3-5. 332 Title of Project: When do eating disorders start? How common are DSM-5 eating disorders? What are the sociodemographic correlates and health related burden of eating disorders in the community? (FOR Code/s):110319 Psychiatry 111714 Mental health Supervisor: Prof Hay Contact: [email protected] Co-supervisor: Dr Slewa-Younan Contact: [email protected] Location of Project: not locality dependant Project Background There is evidence that the distribution and determinants of eating disorders in the community is changing with increasing numbers of men and people from disadvantaged backgrounds with eating disorders. This project has potential for the student to also develop their own alternate or additional ideas and questions from previously collected data. Aim of Study: To investigate prevalence and sociodemographic determinants of eating disorders. Methods: A nested study within a large community survey conducted in 2014 with comparative data from 1995, 1998, 2005 and 2008/9 surveys in South Australia. Ethics Application Requirements: HREC is obtained. The student and the nested project will need to be added to current study investigators. Key References: Mitchison, D., Hay, P., Slewa-Younan, S., & Mond, J. (2012). Time trends in population prevalence of eating disorder behaviors and their relationship to quality of life. PloS one, 7(11), e48450. Mitchison D, Hay P, Slewa-Younan S, Mond J.The changing demographic profile of eating disorder behaviors in the community.BMC Public Health. 2014 Sep 11;14(1):943. 333 Title of Project: Idiopathic toe walking: Can a novel exercise program to address sensory and motor skill challenges be beneficial? (FOR Code/s): 11 Medical and Health Sciences, 111403 Paediatrics, 110603 Motor Control, 730299 Public Health Supervisor: Dr Stef Penkala Contact: Ph 4620 3742, email [email protected] Location of Project: Campbelltown Project Background Gait anomalies in early childhood are a concern for parents and common source of health professional referral. Toewalking defined as the absence of heel contact can be a normal gait variant until 3 years of age (1). However, aetiology including disease, neurological influences and trauma, require screening (1). In the absence of medical conditions, persistent toe walking beyond 3 years of age is considered idiopathic, effecting around 12 % of the paediatric population (2). While idiopathic toe walking (ITW) has no medical cause, links to speech, language (3) and sensory processing (4) difficulties associated with vestibular and sensory anomalies are reported. In a case control study (n= 60) children with ITW demonstrated hypersensitivity of vibration perception threshold (p<0.001), lower Standing Walking Balance subtests (p=0.47) and motor proficiency (p=0.001), compared to norms (4). A range of treatments have been advocated in the management of toe walking including, surgery, casting, stretching, botulinum toxin type A injections and orthotics, particularly in the presence of tight calf structures. However, toe walking can persist beyond the resolution of tight calf structures (5). Interventions beyond the ‘structural’ framework require consideration. Given the links between proficient sensory and motor control with physical activity participation, ITW interventions that can address sensory and motor skill challenges may be beneficial. This study will investigate a novel exercise program to address sensory and motor skill challenges in children with ITW. Aim of Study: The aim of the study of the study is to investigate the benefits of a novel exercise program to address sensory and motor skill challenges in children with ITW. Methods: This study will use a case-control design. Children with ITW will be recruited and screened with the Toe Walking Tool (6) for inclusion. Children will be asked to participate in 8 to 12 exercise sessions challenging sensory and motor input. Pre and post measures will include vibration perception threshold, Standing Walking Balance subtests and motor proficiency. Ethics Application Requirements: NEAF Required Key References: 13. Williams CM, Timey P and Rawicki B Have We Progressed in our Knowledge of the Causality and Treatment of this Gait Type? JAPMA 2014, 104:3 253-61 14. Fox A, Deakin S, Pettigrew G, Paton R: Serial casting in the treatment of idiopathic toe-walkers and review of the literature. Acta Orthop Belg 2006, 72:722-730. 15. Shulman LH, Sala DA, Chu MLY, McCaul PR, Sandler BJ. Developmental implications of idiopathic toe walking. J Pediatr. 1997, 130:541-546. 16. Williams CM, Tinley P, Curtin M, Wakefield S and Nielsen S. Is Idiopathic Toe Walking Really Idiopathic? The Motor Skills and Sensory Processing Abilities Associated With Idiopathic Toe Walking Gait. J Child Neurol 2014, 29: 71 17. Eastwood DM, Menelaus D, Dickens RV, Broughton NS, Cole WG. Idiopathic toe-walking: does treatment alter the natural history? J Pediatr Orthop B. 2000, 9:47-49. 18. Williams CM, Tinley P and Curtin M The Toe Walking Tool: A novel method for assessing idiopathic toe walking children. Gait & Posture 2010, 32: 508–511 334 Title of Project: Beliefs about dealing with Posttraumatic Stress Disorder Alone Amongst Refugees (FOR Code/s): 110319: Psychiatry 111714: Mental health Supervisor: Dr Shameran Slewa-Younan Contact: [email protected] Co-supervisor: Sanja Lujic Location of Project: not locality dependant Contact: [email protected] Project Background: Resettled refugees are a particularly vulnerable group (Slewa-Younan, et al 2014). They have very high levels of mental health problems, in particular, trauma-related disorders, but very low uptake of mental health care. Evidence suggests that poor “mental health literacy” (MHL), namely, poor knowledge and understanding of the nature and treatment of mental health problems is a major factor in low or inappropriate treatment-seeking among individuals with mental health problems (Jorm, 2012) . A recent paper (Slewa-Younan, et al submitted) noted that a high level of participants believed that dealing with the problem such as PTSD alone would be helpful (58%). This was almost 10 times greater than number of participants (6%) in the 2011 NSMHLS who endorsed dealing with the problem alone as helpful and indicates an immediate area for improving the mental health education of refugees. Previous research on factors associated with dealing with mental health problems alone have demonstrated associations with the male gender and beliefs the disorder described is self-limiting and due to personal weakness (Jorm et al 2006). Further researchis need in order to examine such associations in refugee samples. Aim of Study: To examine what are the demographic and clinical characteristics of those who believe that dealing with a problem of PTSD alone would be helpful. This would allow for the development of target mental health promotion programs amongst refugees. Methods: Data for this study will be obtained from a community survey of MHL of Iraqi refugees conducted in 2013. Ethics Application Requirements: HREC is obtained. The student and the nested project will need to be added to current study investigators. Key References: Slewa-Younan S, Uribe, M G, Heriseanu A, Hasan T. (2014) A systematic review of post-traumatic stress disorder and depression amongst Iraqi refugees located in Western countries. Journal of Immigrant and Minority Health, In Press, DOI 10.1007/s10903-014-0046-3 Jorm AF, Kelly CM, Wright A, Parslow RA, Harris MG, McGorry PD: Belief in dealing with depression alone: results from community surveys of adolescents and adults. J Affect Disord 2006, 96(1-2):59-65. Jorm, A. F. (2012). Mental health literacy: empowering the community to take action for better mental health. Am Psychol, 67(3), 231-243. doi: 10.1037/a0025957 335 Title of Project: Lower limb injury and bushwalking shoes: Barriers and facilitators for ‘green exercise’ (FOR Code/s): 11 Medical and Health Sciences, 110604 Sports Medicine, 730220 Injury Control, 730299 Public Health Supervisor: Dr Stef Penkala Contact: Ph 4620 3742, email [email protected] Location of Project: Campbelltown Project Background Mental health is one of Australia's National Health Priority Areas. In Australia in 2007, 14.4% (2.3 million) of people aged 16-85 years were reported to have a lifetime anxiety disorder with symptoms over a 12 month period (1). By 2030, anxiety/depression and ischaemic heart disease are predicted to be two of the three leading causes of illness globally (3). Effective and sustainable interventions to manage anxiety disorders are needed to optimise well-being and opportunities to engage in productive social and working lives. Self-help interventions such as exercise can be positive (2). Findings from a developing body of research indicate that physical activity in the natural environment, ‘green exercise’ has additional positive psychological benefits including reductions in anxiety (4,5). In Australia, bushwalking is a viable form of ‘green exercise’ without the financial burden of gym or sports club membership and fees. Additional benefits of the visual environment can profoundly affect the sense of physical and mental well-being. However, research indicates that a significant number of adults as well as children report foot and shoe-related problems which can hinder daily physical activities like walking (6,7). ‘Underfoot’ events including slips, trips, falls and ankle spranis are the most commonly reported in outdoor ‘adventure’ sports (8). Optimal shoe recommendations are essential to ensure shoes meet the demands of the individual and activity. Despite the wide range of bushwalking shoes available, little is known about footwear literacy/shoe attributes which can be beneficial or detrimental for foot heath, or the contribution to green exercise participation. Aim of Study: 1) To investigate shoe attributes commonly recommended by adventure store staff, and experienced bushwalkers for people purchasing shoes for bushwalking. 2) To investigate peoples footwear experience when participating in green exercise, and the facilitators and barriers ( i.e. shoe-related foot problems, footwear literacy). Methods: Focus groups and semi-structured interviews will be conducted with adventure store staff, experienced bushwalkers and novice bushwalkers. Responses will be transcribed verbatim and categorised to develop a meaningful data framework using a constant comparison technique. Ethics Application Requirements: NEAF Required Key References: 1) Australian Bureau of Statistics (2007) National survey of mental health and wellbeing. Cat No 4326.0 2) Merom et al (2008) Promoting walking as an adjunct intervention to group cognitive behavioural therapy for anxiety disorders – A pilot group randomized trial. Journal of Anxiety Disorders 22: 959-968 3) Mathers CD, Loncar D (2006) Projections of Global Mortality and Burden of Disease from 2002 to 2030. PLoS Med 3(11): e442. doi:10.1371/journal.pmed.0030442 4) Mackay GJ & Neill JT (2010) The effect of “green exercise” on state anxiety and the role of exercise duration, intensity and greenness: a quasi-experimental study. Psychology of Sport and Exercise 11: 238-245 5) Pretty (2005) The mental and physical health outcomes of green exercise. International Journal of Environmental Health Research. 15(5): 319 – 337 6) Garrow, A. P., Silman, A. J., & Macfarlane, G. J. (2004). The Cheshire Foot Pain and Disability Survey: a population survey assessing prevalence and associations. Pain, 110(1-2), 378-384. 7) Penkala S, Harris L, Hunt A and Naughton G (2010) Foot complaints of children aged four to twelve years, sex differences and activity – a cross-sectional survey of parents. Journal of Science and Medicine in Sport 12(2): 107 8) Bentley TA, Cater C and Page SJ. Adventure and ecotourism safety in Queensland: Operator experiences and practice. Tourism Management 31 (2010) 563–571 336 Title of Project: Sexual health of migrant women from culturally and linguistically diverse (CALD) groups: An international comparison (FOR Code/s): 111714; 111799 Supervisor: Professor Jane Ussher Contact: [email protected] Co-supervisor: Associate Professor Janette Perz Contact: [email protected] Location of Project: Centre for Health Research, Building 3, Campbelltown Campus Project Background Researchers and policy makers concerned with the quality of life (QOL) of culturally and linguistically diverse (CALD) populations recognise that sexual and reproductive health (SRH) is a key component of women’s QOL, with utilisation of reproductive and sexual health services associated with positive mental health. However, these services are underutilised by CALD migrant communities, resulting in lack of appropriate information for informed decisionmaking and low use of preventative measures associated with SRH. This can lead to risk of poorer reproductive and sexual health outcomes, as well as long term health costs to the community in alleviating SRH difficulties and distress. It has been acknowledged that there is a need for health providers to understand the cultural constructions and SRH practices across different CALD populations in order to provide comprehensive SRH care and health information, and increase service utilisation. However, the majority of SRH research to date has conceptualised migrants as a homogenous population, which negates variations which occur within and between cultures, the complexity of culture as a concept, and intersections of SRH and cultural background with other social structuring factors, such as age, social class, religion, geographical location and relationship context. The primary focus of SRH research has also been on Vietnamese or South-East Asian populations, examining pregnancy, childbirth, and post-partum experiences, with only a minority of studies examining sexual health. This results in the marginalisation or invisibility of SRH experiences and needs in other CALD migrant groups, an absence of knowledge about many aspects of CALD sexual health, and SRH in younger unmarried women being overlooked. This ARC funded international interdisciplinary project aims to examine the experience and construction of sexual health in recent CALD migrant women from a range of cultural backgrounds and age groups living in Sydney, Australia and Vancouver, Canada. Aim of Study: 1. To investigate the experiences and constructions of sexual health, for recent migrant women from CALD communities in Australia and Canada, focusing on sexual health practices (e.g. sex before marriage, consent), contraception knowledge and use, sexually transmitted infections, sexual pain, satisfaction and desire, and sexual changes associated with reproductive events (e.g. peri-natally; menopause); 2. To adopt an intersectional approach to examine the intersections of gender, cultural and geographical background, religion, time since migration, and age in relation to sexual health and sexual embodiment. Methods: In depth one to one interviews and focus groups, analysed through thematic analysis. Honours students would conduct interviews within one cultural group, and also have experience of being part of the broader study team. Ethics Application Requirements: Ethics approval has been achieved in Sydney and in Vancouver Canada. Key References: Allotey, P., et al., Reproductive health for resettling refugeee and migrant women, in Journal of Health Issues. 2004. p. 12-17 Gagnon, A.J. and L.M.C. Robinson, A systematic review of refugee women’s reproductive health, in Refuge. 2002. p. 617. Georgiadis, K., Migration and reproductive health: A review of the literature. 2008, Department of Anthropology, UCL: London. Urquia, M.L., etal Revisiting the immigrant paradox in reproductive health: The roles of duration of residence and ethnicity. Social Science & Medicine. 2012; 74(10): p. 1610-1621. Ussher, J.M., Perz, J. et al. Purity, Privacy and Procreation: Constructions and Experiences of Sexual and Reproductive Health in Assyrian and Karen Women Living in Australia. Sexuality and Culture. 2012 16 (4) 467-485 337 Title of Project: Tenacity and removal of substances on different types of hard surface encountered in hospital, food industry and forensic settings. (FOR Code/s): 111705 Supervisor: Chris Derry Contact: [email protected], 45701731 Co-supervisor: Greg Whiteley Contact: Location of Project: Laboratory Project Background: The nature of hard surfaces is known to play a major role in the adhesion and intentional removal of substances, both in hospital, food-industry and forensic settings. In the hospital setting, contamination of surfaces with substances containing multi-drug resistant organisms (MDRO) plays a major role in hospital cross-infections. In the food industry adhesion of material to working and machine surfaces is a critical determinant of the efficacy of the cleaning process. In the forensic setting, surface type plays an important role in the adhesion of different types of stains and their removal. The project supervisors are currently carrying out a study into innovative methods for the monitoring of cleaning efficacy of surfaces in the healthcare setting in the reduction of hospital cross-infection, in particular with multiple drug resistant organisms (MDRO). Part of this involves a sub-study into the tenacity and removal of substances from a range of surfaces, which is the topic of the proposed honours study. There will be opportunities for students to add substances of particular interest to themselves into the assessments, extending the study to food and forensic science. Aims of Study: i. To develop a methodology for measuring the level of contaminant on surfaces ii. To carry out washability testing using surface type, contaminant type, cleaning pressure, cleaning material and cleaning chemicals as variables. Methods: Using proxy substances including bacterial cell suspensions, biofilm, yoghurt and raw meat exudate a series of measurements will be carried out to determine their tenacity on different surfaces, and their removal under the action of different cleaning materials and agents using a Sheen 903/PG washability tester. Surfaces used will include laminate, glass, PVC and stainless steel. A new unit has been purchased for this work and industry experts from Whiteley Chemicals will assist in startup. The student will carry out innovative techniques in residue monitoring as part of this work. Ethics Application Requirements: Substances which do not require extraction from humans will be used as proxies for surface contaminants. If the project is extended to specific crime-scene substances such as human blood, approval may be required. Key References: Whiteley, GS , Derry, C., Glasbey, T. Reliability testing for portable adenosine triphosphate bioluminometers. Infection Control and Hospital Epidemiology 2013; 34: 538-540. Whiteley, GS , Derry, C, Glasbey, T. The comparative performance of three brands of portable ATP-bioluminometer intended for use in hospital infection control. Healthcare Infection 2012; 17: 91-97. Whiteley GS, Derry C. The importance of practical zero in cleaning performance indicators. Abstracts of the 14th Congress of the International Federation of Infection Control, October 12-15, 2011, Mestre/Venice. IFIC, 2011, Craigovan, Northern Ireland. 338 Other Medical & Health Services 339 Title of Project: Mass Spectrometry for the early diagnosis of Atherosclerosis (FOR Code/s): 119999 Supervisor: David Harman Contact: 4620 3909 Co-supervisor: Aiden O’Loughlin Contact: 46203767 Location of Project: School of Medicine, Campbelltown Campus Project Background Atherosclerosis is a serious disease associated with hardening of the arteries and can lead to fatal heart attack or stroke. This sneaky disease can remain without symptoms until quite advanced. Atherosclerosis is caused by a build up of plaque on the walls of blood vessels, a layer composed mainly of fat, cholesterol and calcium deposits. Diagnosis is based on a combination of medical and family histories, physical examination and a number of expensive or invasive tests. Currently there is no single, reliable test to enable diagnosis of atherosclerosis while in the very early stages, where intervention will be most effective. Lipids (fats and oils) are a class of compounds which show great promise in medical diagnostics. Accordingly, we would like to analyse the lipid composition of atherosclerotic plaques in order to determine whether there are compounds specific only to this disease. A successful discovery may form the basis of a diagnostic test. The Honours candidate will be supervised by a practicing cardiologist and analytical chemist. Aim of Study: The ultimate goal is to develop a non-invasive and reliable test for early-stage atherosclerosis based upon a lipid biomarker, using the sensitive analytical technique of mass spectrometry. This project will make vital steps towards this end goal. Methods: Atherosclerotic plaques obtained from animals and/or cadavers will be pulverized and the lipids chemically extracted using a chloroform/methanol solvent mixture. The resulting lipids will be separated by ultra performance liquid chromatography (UPLC) and then detected by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Identification of lipids will be undertaken with the aid of tabulated data in the literature. Quantification of promising lipid markers will be attempted it time permits. Ethics Application Requirements: Ethics approval will be required to obtain atherosclerotic plaques from cadavers and/or animals. 340 Education Including: Curriculum & Pedagogy 341 Curriculum & Pedagogy 342 Title of Project: Understanding the lives of global Health and Physical Education teachers in NSW schools (FOR Code/s): 1106, 1302 Supervisor: Bonnie Pang Contact: 98525413 Co-supervisor: TBA Contact: TBA Location of Project: Werrington South Project Background This project is concerned with the teaching experiences of HPE teachers with migrant backgrounds in NSW schools. Australia, along with the United States, Canada and New Zealand, has a strong and sustained history of immigration. One of the consequences of immigration is that Australia is characterized by a wide degree of cultural, linguistic, ethnic and religious diversity. Research shows that there is an increase in the global movements of teachers and that the Australian teaching workforce is becoming more diverse and bi/multilingual. The issue of this ‘super diversity' is central to Australian schooling. Aim of Study: This study aims to identify a range of factors including HPE teachers' classroom experience, assets, mobility, aspirations and cultural factors that influence their perceptions and experiences in teaching in Australia. This focus is critical to an understanding of HPE teachers' contemporary Australian migration experience and to Australia's HPE education in relation to Asian engagement in the Asian century. Methods: This study is underpinned by critical and socio-cultural perspectives. A combination of participatory visual methods, observations and interviews will be employed. Ethics Application Requirements: Ethics clearance will be sought from the UWS Human Research Ethics. Key References: Reid, C., Collins, J., & Singh, M. (2014). Goodbye ‘Mr Chips’: The Global Mobility of Australian-Educated Teachers. In Global Teachers, Australian Perspectives (pp. 135-168). Springer Singapore. Vertovec, S. (2007). Super-diversity and its implications. Ethnic and racial studies, 30(6), 1024-1054. 343 Title of Project: The ‘Healthy Environments and Active Living for Young People” (HEAL-YP) Project (FOR Code/s): 1106, 1302 Supervisor: Dr. Bonnie Pang Contact: 98525413 Co-supervisor: TBA Contact: TBA Location of Project: Werrington South Project Background The importance of built environment and healthcare infrastructures to health and physical activity is well documented in research. However, the lack of understanding of the everyday lives from young people’s perspectives about their built environment is what current research and policy makers might have overlooked and taken for granted. Aim of Study: The purpose of this study is to explore the relationships between young people’s perceptions, the built environment, and socio-cultural factors that shape their (in)active health and physical activity in their living area in Greater Western Sydney. Methods: This study is underpinned by critical and socio-cultural perspectives. A combination of participatory visual methods, observations and interviews will be employed. Ethics Application Requirements: Ethics clearance will be sought from the UWS Human Research Ethics. Key References: Malone, K. (2013). "“The future lies in our hands”: children as researchers and environmental change agents in designing a child-friendly neighbourhood." Local Environment 18 (3):372-395. doi: 10.1080/13549839.2012.719020. Smith, K., and Kotsanas. C. (2014). "Honouring young children’s voices to enhance inclusive communities." Journal of Urbanism: International Research on Placemaking and Urban Sustainability 7 (2):187-211. doi: 10.1080/17549175.2013.820211. 344 Title of Project: Health and Physical Education and Physical Activity in the Lives of Ethnic Minority Girls in Western Sydney (FOR Code/s): 1106, 1302 Supervisor: Bonnie Pang Contact: 98525413 Co-supervisor: TBA Contact: TBA Location of Project: Werrington South Project Background Participation levels in physical activity and the health status of young people are pressing issues in many Western countries. However, socio-cultural and educational experiences of ethnic minority young people, as well as the effect of inequalities upon them, remain under-examined. Minority ethnic young people are identified as ‘bodies-atrisk‘ because they do not conform to the physical activity and health regimes of contemporary Western societies. Socio-cultural researchers have argued that the dominant understandings of an ideal body and the ‘bodies-at-risk’ discourse have possibly overlooked different or alternative meanings of health, physical activity and bodies that could be significant to girls from English as Additional Language/Dialect backgrounds (EAL/D) in Western Sydney. Aim of Study: This study aims to understand the perceptions and experiences in Health and Physical Education (HPE) and physical activity of girls with EAL/D backgrounds in Western Sydney schools. Methods: This study is underpinned by critical and socio-cultural perspectives. A combination of participatory visual methods, observations and interviews will be employed. Ethics Application Requirements: Ethics clearance will be sought from the UWS Human Research Ethics. Key References: Gard, M., & Wright, J. (2001). Managing uncertainty: obesity discourses and physical education in a risk society. Studies in philosophy and education, 20, 535-549. doi: 10.1023/A:1012238617836 Pang, B., Macdonald, D., & Hay, P. (2013). “Do I have a choice?” The influences of family values and investments on Chinese migrant young people’s lifestyles and physical activity participation. Sport Education and Society. doi: 10.1080/13573322.2013.833504 345 Title of Project: Exploring the strengths of PDHPE students in health and wellbeing (FOR Code/s): 1106, 1302 Supervisor: Bonnie Pang Contact: 98525413 Co-supervisor: TBA Contact: TBA Location of Project: Werrington South Project Background Pang and Macdonald (In press) indicated that to promote student inclusion and engagement and to move beyond a traditional deficit approach, such as remedial interventions, requires utilizing a strengths-based approach which recognizes an array of knowledge and capabilities that students bring to education. The concentration on asset building rather than deficit/risk reduction is further substantiated by the establishment of a strengths-based approach as one of the five key propositions of the new Australian Health and Physical Education Curriculum (ACARA, 2012). Aim of Study: The study aims to explore PDHPE students’ perceived strengths in relation to their educational experiences in health and wellbeing units. Results have implications for promoting a positive learning experience to many students who are the first family members to attend university, come from low socioeconomic families and have ethnically diverse backgrounds. Methods: A combination of qualitative and quantitative research methods. Ethics Application Requirements: Ethics will be sought from the UWS Human Research Ethics. Key References: Pang, B., & Macdonald, D. (In press). Recognizing young Chinese Australian’s perceived resources within and beyond schooling. Pedagogy, Culture and Society. Yosso, T. J. (2005). Whose culture has capital? A critical race theory discussion of community cultural wealth. Race, Ethnicity and Education, 8(1), 69-91. doi: 10.1080/1361332052000341006 346
© Copyright 2024