Identification Of Key Enzymes Required For Efficient Post-translational Modification And Multimerisation Of Adiponectin
Funder
National Health and Medical Research Council
Funding Amount
$92,364.00
Summary
Obesity is a major national and global health issue, with 62% of adult Australians being overweight/obese, associated with a number of diseases such as type 2 diabetes and cardiovascular disease. Fat tissue secretes hormones and dysregulation of these hormones contributes to the development of obesity-associated disease. This project aims to define processes governing the secretion of one key hormone and ultimately to identify targets for the treatment of obesity-associated complications.
The Role Of Estrogen-receptor Alpha (ERa) In The Pathogenesis Of Diabetes And Cardiovascular Disease.
Funder
National Health and Medical Research Council
Funding Amount
$374,757.00
Summary
Cardiovascular disease (CVD), including heart attack and stroke, causes more deaths in Australia than any other disease. A major risk factor for CVD is diabetes, which affects more than 1 million Australians. Therefore, treating diabetes will reduce the number of people likely to die from CVD. This project aims to investigate a recently identified role for estrogen in the protection against diabetes. If successful, findings from this project may lead to new treatments against diabetes and CVD.
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
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.
Metabolic Stress Sensing By AMPK: Implications For Energy Balance And Isoform-targetting Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$632,188.00
Summary
Metabolic diseases such as obesity, type 2 diabetes and cardiovascular disease impose enormous medical and economic burdens on Western societies. Our research is focussed on the enzyme AMP-activated protein kinase (AMPK) which acts as the fuel gauge of the cell and is a promising drug target for combating metabolic diseases. Our discoveries provide critical insight on how AMPK is switched on by both energy demand and drugs, and will greatly assist development of AMPK-targetted therapeutics.
Regulation Of Protein Kinases And Their Substrates
Funder
National Health and Medical Research Council
Funding Amount
$553,197.00
Summary
Our research is concerned with the control of the body's energy metabolism via an enzyme called AMPK. This enzyme is at the hub of metabolic control in response to diet and exercise. AMPK controls energy expenditure in response to demand as well as appetite. It is well recognized that diet and sedentary life-styles are major contributors to obesity and cardiovascular disease. We are testing how a new drug activates AMPKand how energy expenditure can be increased.
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
Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contrib ....Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contribute to our basic knowledge of these processes, provide invaluable information about the specific genes and proteins involved, and provide direct information about the therapeutic potential of specific drugs or inhibitors designed to target this oxygen response in human disease.Read moreRead less