Identifying A Novel Role For Pigment Epithelium-derived Factor In Obesity-related Metabolic Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$361,637.00
Summary
Obesity is an important factor contributing to insulin resistance and type 2 diabetes; however, the factors linking these disorders are not well defined. A protein called PEDF is elevated in obesity and type 2 diabetes. This project will examine how PEDF causes insulin resistance and whether blocking PEDF's actions prevents insulin resistance. Successful completion of this project may lead to therapeutics that reduce the risk of developing type 2 diabetes.
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.
Control Of Anabolic And Catabolic Pathways By AMPK
Funder
National Health and Medical Research Council
Funding Amount
$946,402.00
Summary
This project focuses on the role of the metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) in the control of glucose and fat metabolism. AMPK has been linked to the regulation of exercise capacity, longevity and the control of insulin sensitivity. This is important for our understanding of the metabolic dimensions of our Nations most important health problems including, type-2 diabetes, cardiovascular disease, obesity, neurodegeneration as well as other age onset diseases.
Action Of PKC Epsilon In Adipose Tissue Regulates Hepatic Glucose Production
Funder
National Health and Medical Research Council
Funding Amount
$906,859.00
Summary
Our previous studies implicated the enzyme protein kinase C epsilon (PKCe) in the development of fat-induced insulin resistance, a key aspect of Type 2 Diabetes. Contrary to expectations we have now shown that animals lacking PKCe only in fat are protected from whole body insulin resistance when fed a high-fat diet. This project will investigate the mechanisms through which PKCe in fat affects insulin action at other tissues, especially liver, to disrupt normal control of blood sugar levels.
Mechanisms Of Oxidised Protein Accumulation In Ageing Cells
Funder
National Health and Medical Research Council
Funding Amount
$429,000.00
Summary
Australia has one of the world's most rapidly ageing populations. It is estimated that in 30 years time over 30% of the population will be over 65; many will suffer from a debilitating, age-related disease. The diseases of ageing represent one of the major health challenges this century. Despite their increasing incidence, our understanding of the underlying causes is limited. A common feature is the accumulation of damaged proteins in cells and tissues. Damaged proteins are usually broken down ....Australia has one of the world's most rapidly ageing populations. It is estimated that in 30 years time over 30% of the population will be over 65; many will suffer from a debilitating, age-related disease. The diseases of ageing represent one of the major health challenges this century. Despite their increasing incidence, our understanding of the underlying causes is limited. A common feature is the accumulation of damaged proteins in cells and tissues. Damaged proteins are usually broken down by the cells and replaced, but in many age-related diseases this process fails. The most common source of protein damage is attack by oxygen-derived free radicals. These are by-products of our body's need for oxygen and can originate from atmospheric pollutants. Oxygen rusts metal, makes fat go rancid and can cause irreparable damage to proteins and other biological molecules. Free radical damage contributes to the development of many age-related diseases such as atherosclerosis and neurodegenerative diseases such as Alzheimer's disease. The accumulation of damaged proteins can cause cell death. Our knowledge of the mechanisms by which cells remove proteins damaged by oxygen and the reasons for their accumulation is limited. In this project we will use a novel technique we have developed to generate oxidised proteins in ageing cells. We will identify cellular mechanisms required for the efficient removal of damaged proteins and those mechanisms which fail in ageing cells. We will focus on a group of proteins which protect damaged proteins from aggregating and accumulating and we will examine how we can prevent the accumulation of oxidised proteins by stimulating the body s defence mechanisms. Since the population of Australia is ageing, diseases of ageing are going to consume an increasing amount of the national health budget. A better knowledge of these cellular mechanisms will allow us to design effective prevention and treatment strategies which are at present lacking.Read moreRead less
Glutathione Transferase Zeta: A Novel Regulator Of Glucose And Lipid Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$604,143.00
Summary
Obesity is a problem of global significance as a cause of preventable illness and death. The many consequences of obesity including cardiovascular disease, type 2 diabetes, cancer and osteoarthritis are an increasing burden on affected subjects and on the health care system. Our recent studies have revealed a novel pathway for the regulation of obesity. This discovery has provided a new target for the development of drugs for obesity and related disorders.
HDAC3 As A Novel Orchestrator Of Lipid Oxidation In The Intestine And Potential Therapeutic Target In Obesity.
Funder
National Health and Medical Research Council
Funding Amount
$526,365.00
Summary
This application will seek to determine whether blocking the HDAC3 protein, specifically in the intestine, represents a novel way of controlling obesity.