Characterising An Important Control Point In Cholesterol Synthesis Beyond HMG-CoA Reductase
Funder
National Health and Medical Research Council
Funding Amount
$480,739.00
Summary
The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol- ....The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol-related diseases.Read moreRead less
Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s diseas ....Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s disease.Read moreRead less
Role Of An Endogenously Synthesised Sterol In Regulating Cholesterol Removal From The Macrophage
Funder
National Health and Medical Research Council
Funding Amount
$276,000.00
Summary
Heart disease remains the greatest killer of Australians and involves accumulation of cholesterol in the artery wall. Cholesterol accumulates in a specific cell-type called the macrophage (literally means ' big-eater'). Once macrophages accumulate cholesterol, they become bloated cholesterol-filled foam cells. The early and persistent appearance of foam cells in diseased artery suggests that foam cells are active participants in the development of heart disease. Prevention or reversal of their f ....Heart disease remains the greatest killer of Australians and involves accumulation of cholesterol in the artery wall. Cholesterol accumulates in a specific cell-type called the macrophage (literally means ' big-eater'). Once macrophages accumulate cholesterol, they become bloated cholesterol-filled foam cells. The early and persistent appearance of foam cells in diseased artery suggests that foam cells are active participants in the development of heart disease. Prevention or reversal of their formation is therfore an attractive target for new therapies to treat heart disease. In this proposal, we address specific questions which will increase our understanding of how best to prevent or reverse foam cell formation. This work may indicate new therapeutic possibilities for combating heart disease.Read moreRead less
Lipid Trafficking At Membrane Contact Sites: The Role Of Oxysterol-Binding Protein-Related Protein 5 And 8 (ORP5 And ORP8)
Funder
National Health and Medical Research Council
Funding Amount
$466,400.00
Summary
Abnormal subcellular lipid distribution is associated with a number of common diseases including cancer, cardiovascular disease, and Alzheimer’s disease. The overall aim of this proposal is to identify and characterize new molecules that regulate the transport of lipids between different cell membranes. Results from the proposed studies will help developing novel therapeutic agents against common human diseases.
Identification And Characterization Of Novel Proteins In Endosomal Cholesterol Transport
Funder
National Health and Medical Research Council
Funding Amount
$540,636.00
Summary
Abnormal subcellular distribution of cholesterol is associated with a number of common diseases including heart disease and Alzheimer’s disease. The overall aim of this proposal is to identify and characterize novel molecules that regulate the transport of intracellular cholesterol. Results from the proposed studies will provide important insights into the molecular mechanisms governing intracellular cholesterol transport and distribution, and will lead to better treatment strategies against hea ....Abnormal subcellular distribution of cholesterol is associated with a number of common diseases including heart disease and Alzheimer’s disease. The overall aim of this proposal is to identify and characterize novel molecules that regulate the transport of intracellular cholesterol. Results from the proposed studies will provide important insights into the molecular mechanisms governing intracellular cholesterol transport and distribution, and will lead to better treatment strategies against heart disease and dementia.Read moreRead less
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
Akt Kinase Signalling, Regulated Vesicular Transport And Lipid Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$337,850.00
Summary
How do metabolic cues tell cancer cells to make more membranes, or fat cells to make more fat? These are some of the questions that underpin this project, which explores the link between cell signalling, protein trafficking and fat metabolism. Specifically, we aim to define the role of an important signalling molecule (Akt) in intracellular transport and activation of a key integrator of fat metabolism (SREBP). This work will have wide-ranging implications for human health and disease.
Niemann Pick Disease Type C And Intracellular Sterol Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$317,741.00
Summary
Abnormal distribution of cellular cholesterol causes Nieman Pick Disease type C (NP-C), and is also strongly associated with common neurodegenerative diseases such as Alzheimer's disease. We aim to understand the molecular mechanisms by which cholesterol is sorted and transported in the cell. Our results may help develop effective therapeutic strategies against NP-C, Alzheimers' disease and other cholesterol related disorders.