Roles Of The Nuclear Growth Hormone Receptor In Cell Proliferation And Survival
Funder
National Health and Medical Research Council
Funding Amount
$429,387.00
Summary
We have discovered that the cell surface receptor for growth hormone travels to the cell nucleus in dividing cells, including cancer cells. Given the role of growth hormone in promoting growth postnatally, we seek to uncover how the nuclear receptor promotes proliferation directly, and by gene splicing. We have identified strong candidates for its direct actions through proteomics, and a DNA binding site for the receptor. Here we will investigate its role in proliferation, gene splicing and DNA ....We have discovered that the cell surface receptor for growth hormone travels to the cell nucleus in dividing cells, including cancer cells. Given the role of growth hormone in promoting growth postnatally, we seek to uncover how the nuclear receptor promotes proliferation directly, and by gene splicing. We have identified strong candidates for its direct actions through proteomics, and a DNA binding site for the receptor. Here we will investigate its role in proliferation, gene splicing and DNA strand break repair after cell irradiation.Read moreRead less
Cancer Risks From Low-dose Ionising Radiation Following Diagnostic Medical Procedures
Funder
National Health and Medical Research Council
Funding Amount
$750,579.00
Summary
Our study investigates cancer risk following exposure to low doses of ionising radiation from medical procedures. Our first major paper linked over 800,000 CT exposures to cancer outcomes in a cohort of almost 11 million young Australians, and found that CT exposure predicted an increased incidence of leukaemia and most solid cancers. In our ongoing work we will incorporate nuclear medicine and other diagnostic x-rays, and estimate radiation dose for individual procedures and to specific organs.
Determinants Of Tissue- And Ligand-Specific Responses At The Mineralocorticoid Receptor
Funder
National Health and Medical Research Council
Funding Amount
$668,485.00
Summary
The steroid hormone aldosterone controls salt balance and hence, blood pressure. It also has been shown to have a significant role in cardiac failure. Although drugs that block the aldosterone receptor are beneficial in the treatment of heart failure, they are limited by potassium retention in the kidney. In order to develop tissue-specific blockers of the aldosterone receptor, it is necessary to identify mechanisms by which the receptor can be activated and/or blocked in specific tissues.
Rotavirus is the main cause of severe diarrhoea in children worldwide. In this project, we aim to understand the nature of the first-line immune response to rotavirus in the gut, and elucidate how RV counteracts this response to promote infection. These studies will increase our understanding of how rotavirus causes disease, and facilitate the choice of rotavirus targets for drug development and improved vaccines.
LRH-1 is a protein that is inappropriately present in cancers of the breast and other tissues. It causes cancer cells to divide and multiply, and therefore it is important to block its activity. There are, however, no treatments available that block LRH-1. This proposal brings together a team of researchers with broad experience. We will use high throughput technologies to identify and characterize novel LRH-1 inhibitors, and demonstrate their efficacy in reducing the growth of cancer cells.
Mechanisms Of Regulating Gene Expression Via Selective MRNA Transport
Funder
National Health and Medical Research Council
Funding Amount
$424,076.00
Summary
A critical step in the gene expression pathway that is altered in cancer is nuclear export of mRNA. We have demonstrated that mRNA export is not constitutive, but highly selective and can regulate distinct biological processes through poorly understood mechanisms. This project aims to dissect the molecular mechanisms of regulating gene expression via selective mRNA transport. This will establish selective mRNA export as a novel area of research in cancer biology.
EAR2: A Novel Driver Of Breast Cancer Proliferation
Funder
National Health and Medical Research Council
Funding Amount
$725,476.00
Summary
Drugs that block oestrogen are effective breast cancer treatments, but many patients are resistant to their effects. This research addresses a protein known as EAR2, that is elevated in breast cancer tissue compared to normal breast. We hypothesise that EAR2 drives breast cancer cell proliferation, and will test this using cell lines and mouse models. We will validate EAR2 as a new therapeutic target, benefitting patients underserved by current hormone therapies.
Altered Nuclear Trafficking And Nuclear Body Dynamics As Drivers Of Ataxin-1 Toxicity
Funder
National Health and Medical Research Council
Funding Amount
$755,190.00
Summary
Ataxias are a large group of neurodegenerative disorders in which balance, motor skills and memory are progressively lost. While mutations in specific proteins do cause certain hereditary ataxias, the mechanisms of their detrimental actions is unclear. Our studies probe the toxic mechanisms of the ataxin-1 protein, focusing on its partners and stress-initiated formation of a toxic hydrogel state. The outcomes will define impacts on cellular protein movement in neurodegeneration more broadly.
Prostate cancer is the most common cancer in men, causing about 3,300 deaths per year. We have identified some small RNAs called microRNAs and other hormone regulators that can interfere with prostate cancer cell growth and signaling via the testosterone pathway. In this application we will be exploring the potential for each of these agents to reduce prostate cancer growth and the possibility that one or more could develop into a therapeutic target in the future.
Understanding How Toxins Interact With Lipid Membranes And Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$598,220.00
Summary
Chronic pain affects one in five Australians and current treatments have limited effectiveness, with only about one third of patients getting meaningful, pain relief. The aim of the current project is to create alternative treatments for pain that can potentially lead to the reduced suffering and improvement of life quality of many Australians. To achieve this aim we propose to study how spider toxins interact with cells and deactivate sensor targets responsible for chronic pain.