Investigation Into The Roles Of Ena/VASP-Like And Protein Phosphatase 4C In DNA Damage Repair Via Homologous Recombination
Funder
National Health and Medical Research Council
Funding Amount
$57,139.00
Summary
The repair of DNA damage is a critical cellular mechanism that exists to ensure genomic stability. This project aims to investigate the role of the proteins Ena/VASP-Like and Protein Phosphatase 4C in DNA damage repair via homologous recombination. The DNA damage response pathway is an important area in the study of cancer and ageing, and the potential role of PP4C and EVL in homologous recombination needs to be investigated further.
Role Of Oxidative Stress In Activating ATM To Protect Against Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
ATM is the protein defective in the human genetic disorder ataxia-telangiectasia (A-T). This project is designed to investigate how this protein is activated by oxidative stress. The study is largely a mechanistic one, to investigate changes occurring in ATM as part of the activation process. There is evidence that ATM exists in the cytoplasm in neuronal cells and understanding its function in these cells may assist in understanding the basis for neurodegeneration in A-T.
Ciliopathies are an emerging group of syndromes in society that have devastating health effects. Ciliopathy patients exhibit a specturm of disorders including polycystic kidneys, extra digits, retinal degeneration and neural tube defects. INPP5E is a gene that is mutated in patients with a ciliopathy syndrome. These studies will determine the role of INPP5E in ciliopathy disease and may identify INPP5E as a novel treatment target.
Fibrosis is a key cause of renal pathology-dysfunction. Relaxin is an endogenous reno-protective factor, and thus has enormous therapeutic potential. However, despite compelling pre-clinical evidence of its efficacy, little is known about relaxin's mechanism of action. These studies will lead to a much better understanding of its signal transduction properties that will allow us to maximise its anti-fibrotic potential; identify new targets for intervention; and design better clinical trials.
The overall goal of the program is to develop novel approaches to slow the progress or prevent neurodegeneration in patients with rare human genetic disorders. The second program is designed to develop novel therapeutics from snake venom proteins. These include proteins with anti-bleeding activity and those with application in wound healing. The third program involves the development of novel biomarkers for the early detection and prognosis in prostate cancer.
We have identified a novel gene, Inpp5e, that when mutated causes a disease similar to Joubert syndrome and MORMS disease which leads to abnormal movements, developmental delays, mental retardation, abnormal breathing and eye movement. We have identified a candidate gene for these diseases and have shown that deletion of this gene in mice results in similar pathology. We aim to determine the mechanism by which Inpp5e regulates human development and disease.