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Study & Careers

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Repair of the cornea to restore vision

Research Unit: Corneal Research
Primary supervisor: Dr Mark Daniell / Professor Greg Dusting
Tel: +613 99298078 / Email : g.dusting@unimelb.edu.au

Severe burns and corneal disease leads to vascularization and ulceration of the corneal surface, which is currently treated by corneal transplants and lifelong anti-rejection drugs. Many countries in the world do not have sufficient donors to meet the increasing demand for this procedure. At CERA we work closely with chemical engineers and veterinary scientists at the University of Melbourne to develop engineered constructs to replace the damaged corneal endothelium.

The current project is to develop a source of corneal endothelium from human induced pluripotent stem cells (iPS cells), and grow these on patented hydrogel films to replace damaged endothelium. Alternatively, the reprogramming of appropriate patient cells direct to corneal endothelium will be explored. Mechanisms of adhesion and proliferation of these cells will be examined, and preclinical transplantation studies will be carried out in sheep in the veterinary facility. This project would be suitable for biomedical science students with an interest in cell biology, pharmacology or ophthalmology to work towards clinical application of this novel technique with an ophthalmologist, stem cell scientist, veterinary scientists and other cell biologists.

 

Identification of protective pathways in mitochondrial disease: what protects retinal cells from Leber’s hereditary optic neuropathy?

Research Area: Genetics, stem cell biology, bioinformatics
Primary Supervisor: Dr Isabel Lopez Sanchez
Tel: +613 8532 1972 / Email: isabel.lopez@unimelb.edu.au

Project suitable for: Honors, Masters, Medical Student (6-month commitment required)

Essential qualifications: BSc or BSc (Hons)

Start date: first or second semester 2018

Project outline: Leber’s hereditary optic neuropathy (LHON) is an inherited mitochondrial disease that can cause sudden onset of blindness predominantly in young men. Amongst people who carry a LHON mitochondrial DNA mutation, some go blind (LHON affected patients) whilst others maintain good vision throughout life (LHON unaffected carriers), indicating that blindness can be prevented. However, no one has investigated the protective factors that prevent vision loss naturally in LHON unaffected carriers.

In this project, we will combine our mitochondrial and stem cell expertise to generate retinal cells using skin cells from LHON affected patients and LHON unaffected carriers. We will then use the latest genomic sequencing technology to identify protective pathways in cells from unaffected LHON carriers.

This project involves the use of a range of techniques in cell biology (cell culture), stem cell biology (cell reprogramming, iPSC generation and differentiation), biochemistry (immunostaining, mitochondrial function assays), molecular biology (DNA extraction, PCR) and bioinformatics.

Development of regenerative therapy for photoreceptor losses using cell reprogramming technology

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

Photoreceptors are light-sensing cells that form the basis of our vision by converting light into electrical signals that can be decoded by the brain.  the loss of photoreceptors is a key hallmark of many blinding diseases, such as retinitis pigmentosa, age-related macular degeneration, and diabetic retinopathy.  These diseases affect millions of patients and cause a significant socis-economic burden on our healthcare system. Currently, there are no effective means to cure blindness once photoreceptors are lost.  We must therefore find a new approach to help restore vision to these patients.  Regenerative therapy to replace photoreceptors has the very real prospect of helping patients to restore vision.

Cell reprogramming could be the key to this critical issue.  This innovative technology relies on converting one cell type into another by rewriting the transcriptome to alter the cell’s identity.  One of the most famous examples is the Nobel prize-winning discovery of induced pluripotent stem (iPS) cells, in which the altered expression of four transcription factors converted adult fibroblasts into stem cells.  Beyond iPS cells, direct reprogramming is now possible by converting one somatic cell type directly to another, such as fibroblasts to neurons, without passing through an intermediate stem cell state.  this project aims to develop cell reprogramming technology to generate new photoreceptors, providing novel regenerative therapy approach to treat photoreceptor loss.  Techniques involved in this project include cell reprogramming, CRISPR/Cas9, transcriptomic analysis, molecular cloning, fluorescent micrscopy and virus generation.

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.

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.