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«Contents Medicine Research Ophthalmology/ Centre for Eye Projects Research Australia Research Projects Surgery Research Medical Bionics/ Bionics ...»

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Contents

Medicine Research Ophthalmology/ Centre for Eye

Projects Research Australia Research

Projects

Surgery Research Medical Bionics/ Bionics

Projects Institute Research Projects

Otolaryngology Honours in Medicine/ Surgery

Research Projects

St Vincent’s Institute Honours in Otolaryngology

Research Projects

O’Brien Institute Graduate Research Degrees

Research Projects

St Vincent’s Hospital Graduate Research Departments Research Scholarships Projects Page | 1 Research Training @ East Melbourne The Melbourne Medical School’s East Melbourne Precinct offers a wide range of exciting, cutting-edge translational research projects through the following Departments: Medicine @ St Vincent’s, Surgery @ St Vincent’s, Otolaryngology, Ophthalmology and Medical Bionics.

Students can also conduct their research in our affiliated research institutes as well as in the various departments/ units within St Vincent’s Hospital itself.

The Precinct currently hosts around 180 Honours and Research students on both the St Vincent’s Hospital and Royal Eye & Ear Hospital campuses.

Projects offered in this booklet can be tailored to suit any of the degrees available – Honours, Masters of Biomedical Science, Masters by Research or PhD.

All support services offered to students on the main university campus are available to our students, as well as additional resources such as dedicated Research Higher Degree Coordinators, a Research Training Committee for help and advice, Research Training Forum and Travel Allowances for eligible research students.

The students have their own Student Society that arranges both educational and social events throughout the year such as a Student/ Supervisor BBQ, movie nights as well as the Annual Retreat Weekend. They also run a bi-weekly Journal Club where students have the opportunity to present their research or discuss areas of research that are of interest to them.

Scholarships Students enrolled through the Precinct eligible to apply for University of Melbourne Honours and graduate research scholarships, including the Faculty of Medicine, Dentistry and Health Sciences’ Trust Fund Scholarships.

We also provide excellent support to help students apply for external scholarships and grants including those offered by the National Health and Medical Research Council, National Heart Foundation and other organisations.

Further Information If you have any questions about our research projects, application process or scholarships please do not hesitate to contact us.

W: www.medicine.unimelb.edu.au/ehac

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Researchers in Medicine @ St Vincent’s undertake projects in a wide range of areas including basic science, population health and clinical epidemiology, with a strong emphasis on translating research discoveries to clinical benefit. The core research foci have been on diabetes and its complications, kidney disorders, vascular disease, nutritional intervention, inflammation and thrombosis.

New areas of activity include epilepsy research, genetics of leukaemia, infectious diseases, inflammatory bowel disease and other gastrointestinal disorders, and health bioinformatics.

Research projects on offer include:

Renal and Cardiovascular Translational Research Group

NOVEL THERAPIES FOR THE TREATMENT OF DIABETIC CARDIOVASCULAR DISEASE

Lab Head: Prof Darren Kelly Supervisors: Dr Amanda Edgley, Dr Michael Zhang, Dr Fay Kong For enquiries about current Honours and PhD projects, please contact Dr Edgley on aedgley@unimelb.edu.au or Dr Zhang on yz@medstv.unimelb.edu.au Diabetes is associated microvascular complications which lead to diabetic nephropathy, cardiomyopathy and retinopathy. Inflammation and scar tissue formation (fibrosis) in these various organs contribute to the decline in organ function in both diabetic and non-diabetic disease. At present there is no effective treatment for organ fibrosis.

The Renal and Cardiovascular Translational Research group is an internationally recognised team focused on developing novel compounds for the treatment of pathological inflammation and fibrosis in diabetic and non-diabetic kidney, heart and eye disease. Our projects adopt a “bench to bedside” approach to research where we evaluate the efficacy of novel therapies on structural and functional aspects of heart, kidney and eye disease using well characterised animal models that mimic the complications seen in humans. We can then assess the underlying mechanism of action of these compounds using specialised molecular and histopathological techniques, complemented with cell culture systems.

As a team, we have contributed to the discovery of several anti-fibrotic compounds that inhibit the progression of diabetic and non-diabetic kidney and cardiovascular disease, with the lead compound, FT011 progressing to phase II clinical trials in humans. To facilitate the clinical development of FT011, the biotech company Fibrotech Therapeutics was founded by the University of Melbourne. Thus the information gained from these studies allows us to rapidly translate preclinical proof of concept data into clinical development for the treatment of both diabetic kidney, heart and eye disease.

A number of projects suitable for Honours or PhD students are available to outstanding and enthusiastic students interested in pursuing a career in research.





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ADIPOCYTE BIOLOGY, INSULIN RESISTANCE AND CARDIOVASCULAR DISEASE

Lab Head: Assoc Prof Andrew Wilson Supervisor: Assoc Prof Andrew Wilson Tel: 03 9288 2675 / Email: andrew.wilson@svha.org.au This project is in the field of metabolism focused on the interaction of obesity, insulin resistance, diabetes and cardiovascular disease (CVD). There is extensive animal and epidemiological evidence to support links between obesity and CVD, however there is relatively limited data about the exact nature of this relationship particularly related to the specific role of the adipocyte. One area that is not well understood is adipocyte function in vivo and how it relates to measures of whole body insulin sensitivity, particularly in those with CVD. There is also hypothesized to be a difference in adipocyte biology between central and peripheral adipocytes although this has not been well shown in humans. Thus, we aim to measure whole body insulin sensitivity in patients with CVD and to relate these findings to adipocyte function in human subjects.

Hypotheses: That whole body insulin sensitivity will relate to adipocyte structure and AMP-activated protein kinase expression in patients with CVD. That central and peripheral adipocytes will have distinct phenotypes in patients with and without IR. That vascular function in vessels from insulin resistant animals and humans will be abnormal.

The aims compare insulin sensitivity in patients with CVD and markers of adipocyte structure and function in adipose tissue from a range of sites including fat as well as muscle, a key site of insulin and glucose metabolism and to assess vascular function in vitro in tissues from insulin resistant animals and humans. Techniques: Immunohistochemistry, molecular biology, vascular benchtop assessments.

BIOMARKERS OF ATHEROSCLEROSIS: FOCUS ON INFLAMMATION

Supervisor: Assoc Prof Andrew Wilson Tel: 03 9288 2675 / Email: andrew.wilson@svha.org.au This project focuses on identification of novel biomarkers of atherosclerosis in human blood and tissue samples. Based on our previous studies, we expect to elaborate a range of novel low abundance proteins upregulated in atherosclerotic cardiovascular disease and to carefully investigate their clinical potential by analysing other established markers. Once key proteins of interest are identified, levels will be measured in patient groups of interest using high throughput techniques to validate these findings and potentially lead to novel diagnostic tests for atherosclerosis that incorporate traditional and novel risk markers to maximise clinical utility.

Our preliminary data suggests that even in patients at high risk of atherosclerosis presenting for angiography, subgroups can be identified who are at significantly higher risk (up to 7 times). Positive findings in this study will greatly facilitate increased understanding of vascular risk and atherosclerosis pathophysiology. Particular focus will be made on inflammatory pathways since these appear to be highly involved at all stages of atherosclerosis pathophysiology.

Page | 4 This study will advance the use of novel technologies and approaches to the elucidation of as yet undefined proteins in CVD. Identification and characterisation of novel protein markers and integration into existing clinical paradigms will assist in development of better non-invasive diagnostic tests for atherosclerosis, aid in targeted screening and therapeutic programmes and direct novel approaches to the investigation of disease pathways.

Hypothesis: That previously unrecognised plasma proteins in patients will be differentially expressed in patients with and without features of atherosclerosis and its complications and will be detected using novel plasma proteomic profiling techniques. Aim 1: To analyse differentially expressed proteins that will elucidate pathophysiological pathways in atherosclerosis identified in patients with and without atherosclerosis using extended plasma profiling. Aim 2: To confirm these findings in a similar cohort of patients at risk of atherosclerosis. Aim 3: To apply candidate biomarkers to established diagnostic and risk paradigms for atherosclerosis and its complications.

Techniques: Proteomics, Bioinformatics Vascular Biology and Blood Cancers Research Group

NOVEL APPROACH TO TARGET INFLAMMATION AND THROMBOSIS

Lab Head: Prof Harshal Nandurkar Supervisors: Prof Harshal Nandurkar, Prof Peter Cowan Tel: 03 9288 2030 / Email: harshal.nandurkar@svha.org.au Deposition of platelets on damaged endothelial cells, which cover the internal surfaces of blood vessels is an important step in the development of a blood clot, or thrombus. Endothelial cells exhibit an endogenous capacity to restrain the coagulation pathway in order to regulate tightly the extent of clot deposited. Our laboratory has identified novel pathways that may provide such control. The 78 kDa glucose-regulated protein (GRP78) functions as an intracellular chaperone responsible for the correct folding of proteins. We have demonstrated that GRP78 is present in the plasma and is localized to the endothelial cell surface by its interaction with thrombomodulin (TM).

In addition, we demonstrated that recombinant GRP78 exhibits potent anti-platelet activity sufficient to prolong in vivo coagulation and prevent venous thrombosis in mice. This project will identify the molecular basis of the activity of GRP78 and study its usefulness in mouse models of stroke, heart disease and cancer-associated thrombosis. The outcomes have direct clinical implications in the management of cardiovascular diseases and other thrombotic diseases.

IDENTIFICATION OF NEW DISEASE PATHWAYS IN ANTIPHOSPHOLIPID SYNDROME

Supervisors: Prof Harshal Nandurkar, Prof Peter Cowan Tel: 03 9288 2030 / Email: harshal.nandurkar@svha.org.au Anti-phospholipid syndrome is an autoimmune disease associated with antibodies that interact with the endothelium and placental circulation to cause miscarriages and thrombosis. It is now known that inflammation and thrombosis mediated by complement activation and tissue factor engagement play a key role in the pathophysiology of this disease. Work in our laboratory has confirmed that endothelial cell surface-anchored enzyme CD39 can regulate thrombosis and

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Our group has demonstrated that over-expression of CD39 protects the endothelium from acute thrombosis. We have developed a murine model of miscarriages and demonstrated that overexpression of CD39 protects from miscarriages and that under-expression predisposes to the disease. This project will utilize antibody isolated from human patients and administered into mice to dissect the biochemical pathways that mediate foetal loss and thrombosis.

DEVELOPMENT OF NEW ANTITHROMBOTIC DRUGS TARGETED TO THE ENDOTHELIUM

Supervisors: Prof Harshal Nandurkar, Prof Peter Cowan Tel: 03 9288 2030 / Email: harshal.nandurkar@svha.org.au We have demonstrated that endothelial CD39 has antithrombotic and anti-inflammatory activity.

We have developed a new antithrombotic targeted to the endothelium by engineering recombinant soluble CD39. We wish to explore its clinical usefulness in models of microvascular thrombosis.

IDENTIFYING THE ROLE OF CHAPERONE INHIBITION IN THE TREATMENT OF MULTIPLE MYELOMA

Supervisors: Prof Harshal Nandurkar, Dr Hang Quach Tel: 03 9288 2030 / Email: harshal.nandurkar@svha.org.au We have demonstrated that the chaperone activity of GRP78 is vital in the survival of plasma cells that constitute the haematological cancer, multiple myeloma. We have developed a strategy to inhibit GRP78 specifically in plasma cells and will explore the usefulness of this approach in combination with conventional chemotherapy using in vitro studies and mouse models of multiple myeloma. We will also explore the role of the haemopoietic microenvironment in the support of plasma cells by the use of state of art laser scanning microscopy.

Clinical Neurosciences Research Group

BIOPOLYMERS AS VEHICLES FOR CONTROLLED DELIVERY OF NEUROLOGICAL THERAPIES IN

EPILEPSY: ASSESSMENT USING LIVE-CELL FAST FLUORESCENCE IMAGING IN BRAIN SLICES

Lab Head: Prof Mark Cook Supervisors: Prof Mark Cook, Assoc Prof Damian Myers Tel: 03 9288 3068 or 9288 3990/ Email: markcook@unimelb.edu.au or damianem@unimelb.edu.au The ability to control delivery of drugs to precise regions of the brain would revolutionise therapy for people with epilepsy and other neurological disorders. The aim of this project is to develop a drugdelivery system using polymeric structures that can facilitate slow-release of neurological therapies.

Regulated release, or possibly timed-delivery, of drugs immediately at onset of seizure offers the possibility of better efficacy and reduced side-effects.

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