The Novel Role Of Eukaryotic Elongation Factor 2 Kinase (eEF2K) In Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$650,531.00
Summary
Atherosclerosis causes build up of cholesterol plaques inside blood vessels that cause heart attacks and strokes. Macrophages are a type of cell that accumulate inside these plaques to make them grow. We work with a molecule called eukaryotic elongation factor 2 kinase (eEF2K), that controls how cells in the body divide and survive. We are studying how eEF2K controls the macrophage build up in plaque to develop new treatments against atherosclerosis that can stop heart attacks and strokes.
A New Monocyte Atherogenic Phenotype In Chronic HIV Disease.
Funder
National Health and Medical Research Council
Funding Amount
$632,037.00
Summary
Most HIV+ people in Australia now die from cardiovascular disease, caused by atherosclerosis or thickening of coronary arteries. The ability of a white blood cell called the monocyte to prevent atherosclerosis is impaired in HIV. This project aims to understand how HIV does this and how we can reverse the effect. Understanding these processes will also help improve treatments to reduce heart disease in people with other chronic inflammatory conditions.
Control Of The Cholesterol Esterification Cycle In Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$150,660.00
Summary
Atherosclerosis is the disease which narrows arteries and causes heart attacks. It is the most important cause of death in Australia. Although certain treatments such as lowering blood cholesterol reduce the incidence of heart attack, the current mortality from this conditions indicates that there is a great need to improve our understanding and treatment of atherosclerosis. In atherosclerotic arteries, cells called macrophages contain excess cholesterol in the form of cholesteryl ester droplets ....Atherosclerosis is the disease which narrows arteries and causes heart attacks. It is the most important cause of death in Australia. Although certain treatments such as lowering blood cholesterol reduce the incidence of heart attack, the current mortality from this conditions indicates that there is a great need to improve our understanding and treatment of atherosclerosis. In atherosclerotic arteries, cells called macrophages contain excess cholesterol in the form of cholesteryl ester droplets. It appears that human cells are very inefficient at clearing such cholesteryl esters, and this may explain why atherosclerosis is difficult to treat. In this proposal we will investigate how macrophages metabolise these cholesteryl esters and how this process can be stimulated. The results of this study should enable novel treatments of this serious condition to be developed.Read moreRead less
Ras Signalling And Cholesterol Efflux From Late Endosomes
Funder
National Health and Medical Research Council
Funding Amount
$276,598.00
Summary
Accumulation of cholesterol is a hallmark of early atherosclerotic lesions, known as foam cell formation. Hence the stimulation of cholesterol removal (efflux) from macrophages has great therapeutic potential. High Density Lipoproteins (HDL) and apolipoprotein A-I (apoA-I) stimulate efflux via activation of HDL-apoA-I receptors and poorly understood signalling pathways. This application is investigating the role of the Ras-MAPK signalling pathway in promoting efflux from late endosomes.
Modulation Of Cell Phospholipids And Membranes By 7-ketocholesterol And Their Role In Cholesterol Efflux.
Funder
National Health and Medical Research Council
Funding Amount
$186,372.00
Summary
Atherosclerosis is a leading cause of death in Australia. The disease is caused by the formation of large deposits of cholesterol in the walls of major blood vessels. This cholesterol comes from cholesterol-carrying particles in the blood which penetrate into the tissue of the blood vessel. They are taken up by the cells of the tissue which become engorged with large amounts of cholesterol and are called 'foam cells'. These foam cells also contain a small but signficant amount of damaged (oxidis ....Atherosclerosis is a leading cause of death in Australia. The disease is caused by the formation of large deposits of cholesterol in the walls of major blood vessels. This cholesterol comes from cholesterol-carrying particles in the blood which penetrate into the tissue of the blood vessel. They are taken up by the cells of the tissue which become engorged with large amounts of cholesterol and are called 'foam cells'. These foam cells also contain a small but signficant amount of damaged (oxidised) forms of cholesterol, called oxysterols. We have found than an oxysterol called 7-ketocholesterol makes it difficult for cells to get rid of excess cholesterol. Therefore this oxysterol may be part of the reason why foam cells develop. This project will study how 7-ketocholesterol blocks cholesterol removal from cells. This may lead to the development of drugs which remove or prevent 7-ketcholesterol accumulation in the blood vessel and so prevent or reverse atherosclerosis.Read moreRead less
A Mechanotransduction Apparatus To Coordinate Epithelial Collective Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$994,596.00
Summary
Epithelial cells migrate as physically coherent collective groups, which is necessary for normal development and is disrupted as cancers progress to become invasive and spread. Collective migration requires communication so that the behaviour of individual cells is properly coordinated. In this project we investigate how the transmission of physical force between cells allows them to communicate; and test how its disruption contributes to cancer invasion.