Steroid hormones, such as oestrogen and cortisol, act in the body by binding a family of proteins (nuclear receptors) that bind directly to the DNA to regulate genes. The mechanisms underlying this process are complex and involve recruitment of additional molecules or coactivators to improve efficiency. Recently a novel coactivator was identified termed SRA, which remarkably is never made into protein in cells, rather exerting its effects as a RNA. We have identified a novel family of proteins t ....Steroid hormones, such as oestrogen and cortisol, act in the body by binding a family of proteins (nuclear receptors) that bind directly to the DNA to regulate genes. The mechanisms underlying this process are complex and involve recruitment of additional molecules or coactivators to improve efficiency. Recently a novel coactivator was identified termed SRA, which remarkably is never made into protein in cells, rather exerting its effects as a RNA. We have identified a novel family of proteins that bind to SRA in cancer cells, and may well play a critical role in regulating how SRA modulates genes. This project seeks to understand how this family interacts with SRA, the functional effects on breast cancer cells, and the detailed 3-dimensional structure of the family members coupled with SRA. This work will provide novel insight into how SRA regulates steroid hormone action, and may create new potential avenues for developing therapeutics in breast cancer.Read moreRead less
Cellular Localisation Of Mineralocorticoid Receptor-mediated Vascular Inflammation And Cardiac Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$476,264.00
Summary
Cardiovascular disease is a major health and economic burden throughout the world, especially in developed countries and is the leading cause of death and disability in Australia, claiming the lives of over 50,000 Australians each year. Heart failure accounts for many of these deaths and the incidence continues to increase. Two recent large scale clinical trials have shown a 30-35% improvement in patient outcome when a blocker for the mineralocorticoid receptor (MR) is included in current best p ....Cardiovascular disease is a major health and economic burden throughout the world, especially in developed countries and is the leading cause of death and disability in Australia, claiming the lives of over 50,000 Australians each year. Heart failure accounts for many of these deaths and the incidence continues to increase. Two recent large scale clinical trials have shown a 30-35% improvement in patient outcome when a blocker for the mineralocorticoid receptor (MR) is included in current best practice therapy for either heart failure or after a heart attack. The mechanisms underlying these benefits remain to be identified. We have shown that the hormone aldosterone and its receptor, the MR, not only play an important role in the development of high blood pressure but also the progression of cardiac disease. Our most recent studies have shown that blocking the MR not only prevents cardiac fibrosis and vascular damage, but also reverses this process. To understand the mechanisms that translate MR signalling into blood vessel damage and cardiac fibrosis we wish to use mice who have the MR gene inactivated in specific cells only. In this way we can identify those cells critical to the disease process and focus our investigations to these cell types. Understanding the cell specific regulatory mechanisms for the MR may enable the development of heart-specfic blockers of the MR that have minimal, if any side effects.Read moreRead less
Effect Zoledronic Acid And Risedronate On The Preservation Of The Femoral Head In A Rat Model Of Perthes Disease
Funder
National Health and Medical Research Council
Funding Amount
$199,750.00
Summary
Perthes Disease (Legg-Perthes Disease) is a common childhood disorder, which leads to collapse and deformity of the growing hip joint. This can lead to arthritis in adult life, as well as a short leg on the affected side. The cause is as yet unknown. A class of drugs called bisphosphonates has been shown to help children with osteogenesis imperfecta (brittle bone disease). We believe, based on our extensive studies of the effect of these drugs on bone healing, that they could also help children ....Perthes Disease (Legg-Perthes Disease) is a common childhood disorder, which leads to collapse and deformity of the growing hip joint. This can lead to arthritis in adult life, as well as a short leg on the affected side. The cause is as yet unknown. A class of drugs called bisphosphonates has been shown to help children with osteogenesis imperfecta (brittle bone disease). We believe, based on our extensive studies of the effect of these drugs on bone healing, that they could also help children with Perthes disease. Although proving to be safe and effective in children with osteogenesis imperfecta, before exposing children with Perthes disease to the risk of any side effects, animal studies are needed. A certain type of rat called the spontaneously hypertensive rat gets a condition almost exactly the same as Perthes disease. This study will treat a large number of these rats and perform detailed study into whether it has a positive effect on preserving the shape of the hip joint, as well as looking into how this actually occurs. A successful outcome would pave the way for trials in children with Perthes disease, and could result in the avoidance of surgery and improved health outcomes for the children.Read moreRead less