Many drugs modulate the function of proteins imbedded in cell membranes. Extensive research has been undertaken to better understand drug interactions with these proteins to improve drug therapies, but there has been relatively little progress in understanding the role of the cell membrane. This project will investigate how the cell membrane influences protein function and then use this information to develop novel drugs for the treatment of neurological disorders.
Sphingosine Kinase: A Target For Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$626,845.00
Summary
Insulin resistance, a characteristic of type 2 diabetes, is linked to abnormal metabolism of lipid (fat) in tissues such as liver and muscle. This project aims to identify a novel pathway which may promote a build up of lipids in liver and therefore leads to the development of type 2 diabetes. This work may provide a basis for understanding and optimizing treatment of insulin resistance by regulating the control of fat metabolism in liver.
Identifying Novel Lipid And Genetic Signatures Of Metabolic Disease In Early Childhood
Funder
National Health and Medical Research Council
Funding Amount
$354,592.00
Summary
Both our genetic makeup and environment can contribute to the development of obesity, diabetes and heart disease. Although onset usually occurs in adulthood, the progression towards disease can start in early life. Early childhood represents an opportunity for intervention to avoid adverse health outcomes in adulthood. This proposal combines two established birth cohorts from Singapore (GUSTO) and Australia (BIS) to examine the genetic and environmental origins of metabolic diseases.
Understanding Sphingolipid Mediators Of Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$643,447.00
Summary
Sphingolipids are a class of lipid metabolites that have a variety of functions within cells. It has been known for some time that an accumulation of excess lipid, including certain sphingolipids, can adversely impact insulin action and glucose metabolism in cells. In this project we will a combination of strategies to test the hypothesis that the sphingolipid profile can be manipulated to have favourable effects on metabolism.
Impact Of Advanced Glycation On Anti-atherogenic Properties Of High Density Lipoprotein
Funder
National Health and Medical Research Council
Funding Amount
$372,471.00
Summary
Type 2 diabetes is a rapidly growing medical problem in Australia and around the world. Diabetes affects human health through its complications and the cardiovascular complications are a cause for major concern. One of the complications is the effect on plasma lipids: it makes cholesterol carrying particles to accumulate in the blood vessels, causing atherosclerosis. We intend to investigate how diabetes modify these particles making them atherogenic.
A New Target For Allergic Inflammation: The Sphingolipid Pathway
Funder
National Health and Medical Research Council
Funding Amount
$588,617.00
Summary
Collectively, allergic diseases contribute immensely to the burden of health care in Australia. Notably, allergic reactions are symptomatic responses to a normally innocuous environmental antigen. Allergic diseases include asthma, hay fever, food allergy, anaphylaxis, insect sting and drug allergy. This project aims to understand the underlying mechanisms associated with allergic reactions such that it may aid in the identification of novel targets for the development of new treatments.
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 Lipid Metabolism By AMP Activated Protein Kinase
Funder
National Health and Medical Research Council
Funding Amount
$478,776.00
Summary
Western communities are experiencing an epidemic of overweight and obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating an enzyme, called AMP-activated protein kinase, that plays a pivotal role in controlling how our bodies control energy metabolism in response to exercise. Improved understanding about how this enzyme regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines ....Western communities are experiencing an epidemic of overweight and obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating an enzyme, called AMP-activated protein kinase, that plays a pivotal role in controlling how our bodies control energy metabolism in response to exercise. Improved understanding about how this enzyme regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines for the treatment of obesity and the prevention of diabetes.Read moreRead less
Regulation Of Secretion Of The Fungal Virulence Determinant, Phospholipase B
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted ....Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted by the disease-causing fungus, Cryptococcus neoformans, and that it is important in enabling the fungus to invade the host's cells and spread around the body from the lungs to the brain, where it can cause meningoencephalitis. PLB is also produced by other disease-causing fungi. The mechanism of PLB secretion is completely unknown. In this project we aim to determine the pathways involved in PLB secretion with the intention of exploiting steps unique to pathogenic fungi, for the future design of new anti-fungal drugs.Read moreRead less
Regulation Of Protein Kinases And Their Substrates
Funder
National Health and Medical Research Council
Funding Amount
$582,000.00
Summary
Western communities are experiencing an obesity epidemic with up to half the population being overweight. Sedentary life styles and high caloric intake are the cause and will contribute to the development of age onset diseases including obesity, diabetes, cardiovascular disease, stroke and neurodegeneration. This project is investigating an enzyme that plays a pivotal role in controlling the body s response to exercise and diet. The key enzyme involved in this process is called the AMP-activated ....Western communities are experiencing an obesity epidemic with up to half the population being overweight. Sedentary life styles and high caloric intake are the cause and will contribute to the development of age onset diseases including obesity, diabetes, cardiovascular disease, stroke and neurodegeneration. This project is investigating an enzyme that plays a pivotal role in controlling the body s response to exercise and diet. The key enzyme involved in this process is called the AMP-activated protein kinase. This work will increase our understanding of the health benefits of diet and exercise. This new knowledge will play a vital role in developing new therapies for promoting exercise and mitigating the effects of diet that will improve health during the ageing process.Read moreRead less