Molecular Mechanisms Of Inherited Hypocholesterolaemias: Impact Of APOB And MTTP Mutations On Lipoprotein Assembly And Secretion
Funder
National Health and Medical Research Council
Funding Amount
$200,213.00
Summary
Inherited low cholesterol levels can be caused by mutations in either of two genes: APOB and MTTP. These genes encode proteins that are critical for the assembly of fat particles in the body. We plan to use cell lines to study how single amino acid changes out of the 4500 in ApoB and the 900 in the MTTP protein affect protein production, binding with other proteins, and fat particle assembly.
Phospholipase Cbeta 1b, A Target To Limit Atrial Dilatation
Funder
National Health and Medical Research Council
Funding Amount
$544,847.00
Summary
We have identified a heart specific protein that is involved in perpetuating dilatation of the upper chambers of the heart and thereby contributing to cardiac disease. Inhibitors of this protein provide a suitable target for therapy to limit heart disease. The current studies aim to test such inhibitors in vivo as proof-of-concept that such treatment effectively limits cardiac dysfunction.
Examining GWAS-identified Loci Of Interest In Predicting Coronary Events In Subjects With Known Coronary Heart Disease: The LIPID Genetic Study
Funder
National Health and Medical Research Council
Funding Amount
$649,940.00
Summary
Can modern genetic analysis identify the genes which predict future heart attacks? We will follow up 4337 patients who have already suffered a heart attack and use the findings from the exciting new technique of GWAS (Gene wide association studies) to study their whole genetic map, select gene markers from thousands of possibilities to identify those at highest risk. This will develop a genetic markers of risk and shed light on previously unsuspected mechanisms of heart disease.
Ischaemia-induced Sarcolemmal Changes And Their Role In Ins(1,4,5)P3 Generation And Arrhythmogenesis
Funder
National Health and Medical Research Council
Funding Amount
$468,750.00
Summary
Studies in our laboratory at the Baker Heart Research Institute over the last several years have identified a novel mechanism causing the development of arrhythmias, a primary cause of sudden cardiac death in heart failure as well as during an acute heart attack caused by acutely reduced blood flow. The reduced blood flow leads to lowered oxygen and nutrients and thus the beating heart cells have insufficient energy to properly maintain function. Under these stressed conditions, cardiac myocytes ....Studies in our laboratory at the Baker Heart Research Institute over the last several years have identified a novel mechanism causing the development of arrhythmias, a primary cause of sudden cardiac death in heart failure as well as during an acute heart attack caused by acutely reduced blood flow. The reduced blood flow leads to lowered oxygen and nutrients and thus the beating heart cells have insufficient energy to properly maintain function. Under these stressed conditions, cardiac myocytes produce large amounts of a small molecule called IP3, which interferes with the normal electrical balance of the cells. Blocking IP3 generation prevents arrhythmias under these acutely ischaemic conditions. In more recent studies, we have identified many of the enzymes responsible for generation of IP3 in heart cells and have defined the properties of the regions of the cell responsible for this response. We now want to establish exactly how a period of ischaemia alters the localization or functioning of the enzymes that are responsible for this pathological change that leads to fatal arrhythmias.Read moreRead less
New CaMKII Therapeutic Targets In Heart Failure With Preserved Ejection Fraction
Funder
National Health and Medical Research Council
Funding Amount
$740,335.00
Summary
Deaths associated with impaired heart muscle relaxation and unstable cardiac cycle rhythm are increasing. The mechanisms by which these pathologies occur are not understood and clinical therapies are lacking. We have novel evidence to suggest that a key signalling protein, CaMKII, is critically involved in the development of these forms of heart pathology. This goal of this project is to identify how CaMKII is implicated in heart failure and dysrhythmia as a basis for designing new therapies.
Atherosclerosis - The Key Roles Of HDL, Cell Cholesterol Metabolism And Vascular Function
Funder
National Health and Medical Research Council
Funding Amount
$7,085,050.00
Summary
Atherosclerosis, an accumulation of cholesterol in the artery wall, is a major cause of illness and premature death worldwide. It is caused by conditions such as low levels of the protective high density lipoproteins (HDLs), diabetes, smoking and abnormal function of arteries, all of which are linked to disorders of cholesterol metabolism. With our expertise in HDLs, cholesterol metabolism and artery function, our research will lead to the development of novel strategies for early detection and ....Atherosclerosis, an accumulation of cholesterol in the artery wall, is a major cause of illness and premature death worldwide. It is caused by conditions such as low levels of the protective high density lipoproteins (HDLs), diabetes, smoking and abnormal function of arteries, all of which are linked to disorders of cholesterol metabolism. With our expertise in HDLs, cholesterol metabolism and artery function, our research will lead to the development of novel strategies for early detection and prevention of atherosclerosis and heart disease.Read moreRead less
Identifying And Developing Novel Therapeutic Approaches For Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$638,517.00
Summary
Increasing rates of obesity, diabetes, and an ageing population increase the risk of heart disease & complications including heart failure (HF), atrial fibrillation (AF), and diabetic heart disease. There is a clinical need for i) improved therapies for patients with HF, AF, and diabetic heart, and ii) biomarkers which more effectively recognise people at risk of heart disease, to prevent clinical events. My research program is designed to develop novel therapies and identify new biomarkers.
Insulin Regulated Aminopeptidase: A New Cardiovascular Target
Funder
National Health and Medical Research Council
Funding Amount
$672,650.00
Summary
Cardiovascular disease, leading to heart attack or stroke is the largest cause of death in Australia. We have evidence that inhibition of a newly described enzyme (IRAP) by angiotensin IV is protective in a model of atherosclerosis. Excitingly we have preliminary data indicating that mice deficient in IRAP have better vascular function therefore we will further investigate this as well as the effectiveness of newly developed IRAP inhibitors in preventing development of cardiovascular disease.
Novel GPCR Transactivation Of Serine Kinases In Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$386,565.00
Summary
All of biology and disease is based on cells receiving signals from hormones and growth factors via cell surface receptors. Cells integrate these signals to give a response which may be cell growth or the secretion of further hormones and growth factors. Signals from receptors can intersect to modify the response. This project will explore a new interaction we have discovered where a hormone activates its receptor to cause the activation of a growth factor receptor potentially providing new drug ....All of biology and disease is based on cells receiving signals from hormones and growth factors via cell surface receptors. Cells integrate these signals to give a response which may be cell growth or the secretion of further hormones and growth factors. Signals from receptors can intersect to modify the response. This project will explore a new interaction we have discovered where a hormone activates its receptor to cause the activation of a growth factor receptor potentially providing new drug targets in cardiovascular disease.Read moreRead less
SHANK3 As A Target To Reduce Hypertrophy And Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$548,908.00
Summary
We have identified a large protein in heart that functions to facilitate the heart's response to disease. The proposed studies will define how this protein mediates responses and whether we can successfully interfere with the process to limit disease progression.