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
A Novel Lipid Sensitive Kinase And Its Role In Obesity-induced Inflammation And Insulin Resistance.
Funder
National Health and Medical Research Council
Funding Amount
$560,045.00
Summary
It is now apparent that obesity leads to chronic low grade inflammation which results in insulin resistance or pre-diabetes. The mechanisms that link obesity-induced inflammation to insulin resistance are not well understood, but involve lipid oversupply. We have preliminary data identifying that a protein, not known to previously play a role in metabolic diseases, is a critical mediator of lipid-induced inflammation. We will investigate the clinical potential of blocking this protein.
Can Blocking Fatty Acid Transport In Myeloid Cells Prevent Insulin Resistance?
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Over the past 5 years it has become apparent that blood cells can become inflamed as people become obese. These inflamed blood cells can contribute to insulin resistance or pre-diabetes. Our hypothesis is that these blood cells become inflamed because they take up fat via fatty acid transporters. Our approach is to knock out one of these fatty acid transporters specifically in blood cells and reduce inflammation and insulin resistance due to overnutrition.
Novel Gp130 Receptor Ligands To Treat Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$708,267.00
Summary
Over the past decade work from our group has identified that a group of cytokines termed the gp130 receptor cytokines can lead to weight loss in animals and humans. Unfortunately, due to side effects, clinical trials using peptides analogues of these cytokines have failed. We believe that we know why this has occurred and we think we have developed new peptides that will alleviate these side effects. This application will test the efficacy of these novel peptides in mammals in vivo.
Sphingosine Kinase As A Target Therapeutic For Obesity Induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$450,390.00
Summary
Obesity is linked to the development of insulin resistance and diabetes, which represent a significant health issue in Australia. A number of factors contribute to the development of insulin resistance, including defective fatty acid metabolism. This study proposes to investigate whether manipulating sphingosine kinase, a key enzyme in lipid metabolism, affects the development of insulin resistance. These studies may identify novel targets for the treatment of insulin resistance and diabetes.
Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-ter ....Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-term strategy: exercise training has low compliance, while chronic TZD use is associated with several adverse side effects (edema, weight gain etc.). We will investigate the metabolic, cellular and molecular mechanisms by which these therapies each exert their positive effect on insulin action with the aim of identifying novel targets for future drug interventions. Read moreRead less
Characterisation of novel gene products that regulate phospholipid metabolism and lipid droplet formation in the yeast saccharomyces cerevisiae. This project aims to study gene products that control lipid storage in the form of lipid droplets. The biogenesis and composition of lipid droplets in plant seeds or algae determine the quantity and quality of oil/biodiesel production.
Mechanisms Of Fatty-acid Mediated Destruction Of Pancreatic Beta Cells
Funder
National Health and Medical Research Council
Funding Amount
$510,476.00
Summary
Type 2 diabetes is associated with obesity, but not all obese individuals develop the disease. Non-diabetic obese subjects are able to compensate for diminished sensitivity to insulin (a general feature of obesity) by enhanced output of insulin from the pancreatic beta-cells of the islet of Langerhans. In diabetics this compensatory mechanism is disrupted. Obesity and Type 2 diabetes are also associated with elevated levels of fatty acids (FAs) in the bloodstream. These can be taken up by the be ....Type 2 diabetes is associated with obesity, but not all obese individuals develop the disease. Non-diabetic obese subjects are able to compensate for diminished sensitivity to insulin (a general feature of obesity) by enhanced output of insulin from the pancreatic beta-cells of the islet of Langerhans. In diabetics this compensatory mechanism is disrupted. Obesity and Type 2 diabetes are also associated with elevated levels of fatty acids (FAs) in the bloodstream. These can be taken up by the beta-cells where they exert both short and long-term effects. In the longer term FAs can be toxic to beta-cells and this is thought to be important in the failure of beta-cell compensation. The project is aimed at a better understanding of the manner by which different types of FAs influence the susceptibility of beta-cells to destruction. It builds on our preliminary results suggesting that the capacity of the beta-cell to convert saturated FAs to unsaturated FAs helps protect them from destruction. Our aim is to examine the mechanisms underlying this protection.Read moreRead less
Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel ta ....Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel targets and strategies for treating obesity. The proposed study will also benefit Australian agriculture by providing strategies to improve oil production from plant seeds. Read moreRead less
The cellular dynamics of lipid droplets: implications for obesity and biodiesel production. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also identify novel com ....The cellular dynamics of lipid droplets: implications for obesity and biodiesel production. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also identify novel compounds and strategies for treating obesity. The proposed study will also benefit Australian agriculture and energy industry by providing strategies to improve the production of plant oil and biodiesel. Read moreRead less