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Study & Careers

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Using patient-specific stem cells to model optic neuropathies

Research Unit: Cellular Reprogramming
Primary supervisor: Dr Raymond Wong
Tel: +613 99298054 / Email : wongcb@unimelb.edu.au

Optic neuropathies represent a group of ocular diseases characterised by loss of retinal ganglion cells. The extreme difficulty in obtaining ocular tissue from living individuals, as well as the lack of good cellular models, represent major barriers to studying and treating optic neuropathies. Recent advances now allow us to reprogram patient’s somatic cells into induced pluripotent stem (iPS) cells, which can give rise to all cell types in the body and proliferate indefinitely in vitro. This project will direct patient-specific iPS cells into retinal ganglion cells to create an in vitro model for studying optic neuropathies. In particular, the student will undertake studies with other team members to investigate the molecular mechanisms underlying disease progression of optic neuropathy, development of reprogramming and differentiation technologies to generate patient-specific retinal ganglion cells, and contribute to the development of ex vivo model to test gene therapy and cell therapy, as well as drug screening to identify bioactive compounds that can rescue the disease in iPS-derived retinal ganglion cells from patients to develop novel treatments for optic neuropathies.

Repair of the heart by stem cells protected with new drugs

Research Unit: Cytoprotection Pharmacology
Primary Supervisor: Dr Hitesh Peshavariya and Professor Greg Dusting
Tel: +613 9929 8143 or 8078 / Email: hitesh.peshavariya@unimelb.edu.au

Heart attack is a sudden catastrophic event in the lives of many people and heart failure is still one of the leading causes of death in Australia and worldwide. After heart attack the body responds to attempt repair by stimulating existing stem cells (called regenerative or progenitor cells) in the blood and bones. Attempts have been made to repair heart muscle using drugs to mobilise regenerative cells in order to prevent progression to heart failure, but these trials had limited success in the clinic. A major hurdle has been that mobilised regenerative cells are insufficient for heart repair in aged people and patients with other cardiovascular diseases such as hypertension, stroke and diabetes. Endothelial progenitor cells (EPCs) play an important role in repair of cardiovascular diseases. In this project we will test whether prostacyclin enhances mobilisation and survival of transplanted EPCs after myocardial infarction in mice.

We will study the intracellular mechanisms of prostacyclin signalling in endothelial progenitor cells and its role in cell mobilisation, homing and differentiation processes, which are all involved in promoting neovascularisation. We will then evaluate blood vessel formation in vivo using endothelial progenitor cell therapy and pharmacological intervention, which modulates prostacyclin signalling, in terms of their contributions to neovascularisation. These studies will use pharmacological, molecular and cell culture tools as well as knockout mice, and mouse models of myocardial infarction.

Non-invasive ocular drug delivery

Research Unit: Drug Delivery
Primary Supervisor: Dr Hong Zhang
Tel: +613 9288 3721/ Email: hong.zhang@unimelb.edu.au

Our research focuses on non-invasive and targeted tools, treatment options and technologies for vision threatening diseases such as endophthalmitis, age-related macular degeneration, glaucoma and diabetic retinopathy. Novel methods such as ocular implant, ultrasound and nanotechnology will be performed. Results from these novel therapeutic studies will be evaluated using histological, immunohistochemical and molecular biological techniques. The information gained from these studies is directly applicable to the clinical setting. Students will be involved in the establishment and optimisation of ocular drug delivery protocols and performing in vitro and in vivo verification studies of these methods; they will also be able to participate in ongoing projects.

Why does aging impair optic nerve recovery from injury?

Research Unit: Glaucoma
Primary Supervisor: Prof Jonathan Crowston
Tel: +613 9929 8378 / Email: crowston@unimelb.edu.au

Glaucoma and other neurodegenerative conditions of the CNS increase with increasing age. The reasons for this are now well understood.

We have developed an optic nerve stress test in experimental mice and demonstrated a clear association between advancing age and impaired recovery after injury. This project will help investigate the key mechanisms that underly this impairment. In particular we are interested in the role of mitochondrial impairment as a major player. Recent data from our lab has shown that diet restriction, exercise and high fat diets can all significantly impact optic nerve recovery and alter age-related vulnerably of the optic nerve to injury. These well established models together with established transgenic mouse lines and sophisticated mitochondrial respiration assays will form the core of this project.

Project outcome: This project will generate fundamental data on the impact of ageing on the ability of a neurone to recovery after injury. The PhD candidate will gain excellent experience in experimental procedures and molecular techniques. Our laboratory has a highly talented group of scientists who work in a stimulating and productive environment.

Identification of surrogate markers for monitoring disease progression in AMD

Research Unit: Macular
Primary Supervisor: Professor Robyn Guymer
Tel: +613 9929 8393 / Email: rhg@unimelb.edu.au

Age-related macular degeneration (AMD) is an eye condition that affects the central vision. It is the leading cause of irreversible blindness in individuals over 50 years of age and is responsible for half of irreversible vision loss in Australia. The focus of the Macular Research Unit at the Centre for Eye Research Australia is on investigating novel treatments for AMD and new biomarkers for monitoring disease progression. The aim of this project is to investigate the relationships between retinal structure and function in people with AMD using novel multi-modal imaging and state-of-the-art functional testing modalities to identify robust surrogate markers for monitoring disease progression in AMD.

Using pluripotent stem cells to model AMD

Research Unit: Neuroregeneration
Primary Supervisor: Dr Alice Pébay
Tel: +613 9929 8165 / Email: apebay@unimelb.edu.au

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. Virtually nothing is known about how or why retinal cells die in AMD; however, genetic background is a significant risk factor. Our research uses stem cells from patients with eye diseases to better understand the underlying cause of diseases. In this project, we will reprogram skin and hair cells from these patients with specific genetic risk associated with AMD into induced pluripotent stem cells, and then drive the stem cells to become retinal pigmented epithelial cells to create an in vitro model in which to study AMD pathogenesis. By examining how these retinal cells die, we expect to find ways to block this process, which is an important step towards developing therapies.

The role of the immune system in AMD

Research Unit: Ocular Genetics
Primary Supervisor: A/Prof Paul Baird
Tel: 03 9929 8613 / Email: pnb@unimelb.edu.au

Age related macular degeneration (AMD) is the leading cause of blindness in Australia. A number of genes have been identified as associated with this disease and point to a major role of the immune system. This project will assess the role of immune genes and immune background through genotyping and sequencing as well as through gene expression studies in patients and donor eye tissue. You will undertake DNA and RNA extraction, genotyping, RT-PCR, RNA Seq and bioinformatics analysis.

Gene and protein analysis in AMD

Research Unit: Ocular Genetics
Primary Supervisor: Associate Professor Paul Baird
Tel: +613 9929 8613 / Email: pnb@unimelb.edu.au

Age related macular degeneration (AMD) is the leading cause of blindness in Australia. A number of genes have been identified in this disease which point to an immune role. A treatment for this disease is available but not all patients do well. This project will assess the role of genes (DNA and RNA) and changes in proteins in the serum of patients based on treatment outcome as well as in patients with different genetic profiles. You will undertake a range of molecular biology techniques including DNA, RNA and protein extraction from patient blood, use RT-PCR, RNA Seq as well as various protein techniques including 2D-PAGE, Mass Spec and bioinformatics analysis.

Gene environment interactions in myopia

Research Unit: Ocular Genetics
Primary Supervisor: Associate Professor Paul Baird
Tel: +613 9929 8613 / Email: pnb@unimelb.edu.au

We have identified a number of genes associated with short-sightedness (myopia). The focus of this project is to investigate the role of genes and environmental factors (such as reading or outdoor activity) on myopia in children. You will have access to a large dataset with collaborators in Sydney as well as involvement in a large international consortium investigating similar changes in myopia. You will undertake a range of techniques including extraction of DNA, molecular biology, genotyping, statistical analysis and bioinformatics.

Gene function in keratoconus

Research Unit: Ocular Genetics
Primary Supervisor: Associate Professor Paul Baird
Tel: +613 9929 8613 / Email: pnb@unimelb.edu.au

Keratoconus is an eye disease affecting the cornea at the front of the eye and usually occurs in teenage years. Its causes are unknown but both genetic and environmental factors are implicated. An immune component to this disease is likely and a number of genes have been associated with keratoconus. This project will assess the role of immune genes and immune background through genotyping and sequencing as well as through gene expression studies in donor eye tissue. You will undertake a range of molecular biology and genetic techniques including DNA and RNA extraction, genotyping, copy number analysis, RT-PCR, RNA Seq and bioinformatics analysis.