Risk Prediction in AMD - Can We Do Better?
This proposal brings together different areas of medicine and biology and applies advances in high throughput computing and big data analysis to aid our understanding and advancement of treatments for the eye disease of age-related macular degeneration; particularly the dry form of disease where there is currently no treatment. It will identify genes that interact with each other as well as with other factors known to be involved in increased risk of AMD such as age, sex of an individual and smoking. The statistical findings will be verified through modelling in human cells derived from AMD patients to identify how these genes influence disease. This work will have a profound impact on how we think of both advanced types (the dry and wet types) of AMD and provide targets for future development of therapies that will improve patient’s lives with this disease.
This proposal brings together experts in computational, genetics and regenerative medicine to unravel how genes, environment and other factors “talk to, or interact with each other” to influence progression of AMD as well as how these different factors influence AMD disease subtypes.
We will use novel computational programs that we have developed to analyse data from 40,000 patient samples collected through the International AMD Genomics Consortium - the world’s largest AMD genome wide association study. Our first aim will identify a compact set of gene variants that represents the most likely combination of genes predicting AMD. We will also identify how different combinations of genes predict the dry and wet forms of AMD. Once these gene risk combinations have been identified we will assess how other factors such as age and smoking impact on these gene combinations. In the second aim, we will use regenerative medicine techniques to test the function of the gene combinations that we have identified. This will be undertaken by using gene editing techniques in stem cell models that use retinal cells similar to those involved in AMD.
This suite of experiments will provide a powerful pipeline to better understand what causes AMD and in particular what gene combinations are involved in either the dry or wet form of AMD. This will have important implications for development of future novel treatments.
About the Researcher
I am a Professor in the Department of Surgery, Ophthalmology at the University of Melbourne. I also head the Ocular Genetics Unit at the Centre for Eye Research (CERA). I have been awarded many national and internationally competitive grants and I am a current recipient of a prestigious and highly competitive 5-year National Health and Medical Research Council of Australia Senior Research Fellowship. I have published over 180 journal articles including in top ranked journals such as Nature Genetics and Lancet and have established an expansive network of collaborations both nationally and internationally to explore AMD. In particular, I am actively involved in international consortia through my work in age related macular degeneration and co-chair working groups. I am frequently invited to participate in and help organise national and international conferences and present at national and international meetings. I am vice president of the Global Eye Genetics Consortium and a member of various committees including the Human Research Ethics Committee at the Royal Victorian Eye and Ear Hospital.
I am passionate about improving people’s lives through maintaining their quality of life for as long as possible. As such, maintenance of our sight is imperative for active participation in the connected age for full enjoyment of life and work. I have worked in medical research for 30 years in areas as diverse as microbiology and children’s cancer but I find eye research and in particular macular degeneration as one disease where we are now beginning to make a real difference to a large number of people. The area of genetic research combined with advances in computational advances as well as regenerative medicine provides a perfect opportunity to advance our understanding of AMD that will have an impact on many millions of people around the world. I am particularly grateful to the BrightFocus Foundation for their support for this project and to you, the donors, who have given your generous support, and I hope to reward your generosity with encouraging developments in this field.
First published on: June 20, 2019
Last modified on: July 17, 2019