The key goal of my research is to understand the role of protein phosphorylation in controlling metabolism, with a special emphasis on the structure and function of members of the AMP-activated protein kinase (AMPK) pathway. This is important because the function and survival of all organisms is dependent on the dynamic control of energy metabolism, with energy demand matched to energy supply.
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.
AMPK Control Of Lipid Metabolism: Role In Regulating Energy Balance And Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$614,437.00
Summary
The control of appetite and maintenance of a lean body mass along with exercise is important for protecting the body against obesity and increased incidence of Type 2 diabetes and cardiovascular disease. We are investigating how the regulation of lipid metabolism controls appetite and body weight and the extent to which these same controls are important for drugs acting to lower blood lipid levels.
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.
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.
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.