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
Alterations In Secretion And Gene Expression In Pancreatic Beta Cells Exposed To Lipid.
Funder
National Health and Medical Research Council
Funding Amount
$425,250.00
Summary
The project is aimed at a better understanding of the way in which fats control gene expression in the pancreatic beta cells of the islets of Langerhans. Because changes in gene expression are to likely to explain why exposure of these cells to fat disrupts their ability to release insulin, identification of these genes could explain why only some obese people develop Type 2 diabetes.
Signaling Pathways To Enhance Potency Of AMPK-targeting Drugs
Funder
National Health and Medical Research Council
Funding Amount
$661,966.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to epidemics of obesity-related metabolic diseases that place enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Our goal is to improve AMPK drug potency by identifying novel processes that sensitize AMPK to drugs.
Assembly And Misassembly Of Mitochondrial Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Mitochondria are the powerhouses in our cells. They burn the carbon fuels we eat and store the energy by making ATP that is used for functions such as muscle contraction and triggering of nerves. Mitochondrial Complex I is a molecular motor that helps to make ATP. “Mitochondrial disease” is often seen when Complex I is not built properly and this results in early childhood death. In this project we will study how Complex I is built and how the mitochondria responds to assembly problems.
The Role Of Accessory Subunits And Assembly Factors In The Biogenesis Of Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$569,987.00
Summary
The mitochondrial respiratory chain produces most of the energy required for our cells to grow and function. Complex I is the first enzyme of this chain and its defects are the most prevalent cause of mitochondrial disease, which often results in infant fatality. Defects in complex I have also been associated with Parkinson's disease and oxidative stress. This study will provide important new information into how complex I is built and what goes wrong to cause disease.
Characterising Complex I Function And Dysfunction In Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The cells in our body produce energy in power plants called “mitochondria”. Mitochondrial disease affects 1 in 5000 live births. Currently there is no cure, but understanding how the genes mutated in mitochondrial disease work is an important step to finding one. Previous research relied on patient samples; however we will employ new technologies allowing us to rapidly model mitochondrial disease in a laboratory setting.
Matching Supply And Demand: How Does Metabolism Fine-tune Signal Transduction?
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
Insulin controls nutrient traffic and disrupting its actions are linked to many diseases: type 2 diabetes, cancer, heart disease. Here, I will test a novel hypothesis that our cells’ metabolic rate, defined by the balance between nutrient supply and energy expenditure, controls how cells respond to insulin. These metabolic regulatory nodes would play a major determinant of many essential functions linked to human health, and thus provide novel therapeutic targets for numerous diseases.
Oxidative Damage and Cell Ageing. This research will benefit Australia by providing a fundamental understanding of how cells age. This will have immediate international impact at the scientific level and will inform strategies to reduce the rate of ageing and alleviation of age-related disorders. In the longer term the research may provide commercial and social outcomes by identifying antioxidant systems that will provide a genuine benefit in reducing ageing.
Identifying The Critical Components Of Growth Factor-mediated Survival Pathways
Funder
National Health and Medical Research Council
Funding Amount
$589,338.00
Summary
The regulation of cell lifespan (cell survival) is controlled by growth factors and lies at the heart of all biological processes. However, little is known of the molecular switches inside cells that either turn survival on or off. We propose to identify and characterize the molecular switches inside cells that control the balance between cell survival and death. Targeting specific components of these switches may provide new approaches for the treatment of cancer and infectious diseases.
Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems ar ....Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems are activated as during the process.Read moreRead less