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.
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
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
Prof Trevor Mori has held an NH&MRC Research Fellowship during 2008-2012. This grant will enable him to continue his research program into 2013-2017. Prof Mori is a biomedical research scientist. His research examines the role of diet and lifestyle on risk factors for cardiovascular disease. He also leads the cardiometabolic team examining risk factors in the Western Australian Pregnancy (Raine) Study.