The Role Of Seipin In Lipid Metabolism And Adipogenesis
Funder
National Health and Medical Research Council
Funding Amount
$397,749.00
Summary
The prevalence of obesity and its related disorders has reached an alarming level in Australia and other developed countries. Obesity is characterized by accumulation of fully-differentiated adipocytes loaded with lipid droplets (LDs). Therefore, understanding the cellular dynamics of LDs and the molecular mechanisms of adipogenesis (adipocyte differentiation) is of crucial importance in our battle against obesity. Our proposed study will help undertand the mechnisams of obesity.
Elucidating Metabolic Dysregulation In Alzheimer’s Disease: Profiling The Peripheral Immune Cell Lipidome To Unravel Pathological Mechanisms.
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Both the immune system and lipid metabolism have been identified to be important in Alzheimer’s disease (AD). With the failures of all clinical trials attempting to treat AD, we seek to determine a way to both better diagnose individuals with AD and to identify people at increased risk. This project uses a novel profiling technique to characterise the lipid composition of immune cells to diagnose, predict risk, monitor the disease and to identify potential disease modifying therapeutic targets.
State Dependent Drug Binding To The Human Ether-à-go-go Related Gene Channel
Funder
National Health and Medical Research Council
Funding Amount
$33,193.00
Summary
Heart rhythm disturbance is a common cause of death in our community. In a subset of patients the heart rhythm disturbance is caused by mutations in genes that encode for special proteins called ion channels. However, even in patients without a mutation certain drugs can cause the same problem. Such drugs need to be identified early in their development but current methods to do this are inaccurate. An understanding of how these drugs disturb the heart rhythm will allow more accurate testing.
Lipoprotein Metabolism And Mutations Of The APOB Gene Causing Familial Hypobetalipoproteinaemia
Funder
National Health and Medical Research Council
Funding Amount
$396,179.00
Summary
Cardiovascular disease is an increasing problem in Australia, however, the cause of atherosclerosis is incompletely understood. A protein, known as apolipoprotein (apo) B, plays a central role in lipoprotein metabolism. Elevated levels of apoB are characteristic of many forms of hypercholestrolaemia. Familial combined hyperlipidaemia and polygenic hypercholesterolaemia are two common inherited disorders of lipoprotein metabolism that are characterised by elevated apoB levels in the blood and ear ....Cardiovascular disease is an increasing problem in Australia, however, the cause of atherosclerosis is incompletely understood. A protein, known as apolipoprotein (apo) B, plays a central role in lipoprotein metabolism. Elevated levels of apoB are characteristic of many forms of hypercholestrolaemia. Familial combined hyperlipidaemia and polygenic hypercholesterolaemia are two common inherited disorders of lipoprotein metabolism that are characterised by elevated apoB levels in the blood and early atherosclerosis. In contrast, familial hypobetalipoproteinemia is a rare inherited disorder of lipoprotein metabolism characterised by very low levels of cholesterol and apoB in the blood and resistance to atherosclerosis and cardiovascular disease. The focus of this research project is to explore the regulation of apoB metabolism using individuals from unique families with familial hypobetalipoproteinaemia. First, we will determine and characterise the alterations in the APOB gene causing the low cholesterol levels in families with familial hypobetalipoproteinaemia. Second, we will determine if these apoB alterations affect the production and-or clearance of blood fats, or lipoproteins in affected individuals, when compared to controls, by performing metabolic studies. The proposed human in vivo metabolic studies will lead to a better understanding of the mechanism(s) involved in the assembly, secretion, transport, and clearance of plasma apoB-containing lipoproteins. Furthermore, these studies may reveal new protective mechanisms and potentially aid in the development of strategies to suppress over-production of apoB-containing lipoproteins in reciprocal conditions such as familial combined hyperlipidaemia or polygenic hypercholesterolaemia.Read moreRead less
I am a lipid biochemist-cell biologist determining the molecular mechanisms of disorders of lipid metabolism and developing treatments for such disorders. The diseases where lipid metabolism plays a key role include cardiovascular diseases (such as coronary artery disease), metabolic disorders (such as diabetes), some infectious diseases (such as HIV) and neurological disorders (such as Alzheimer disease).
ABCA1 _ An Intersection Between Infection, Atherosclerosis And Metabolic Disorders
Funder
National Health and Medical Research Council
Funding Amount
$653,827.00
Summary
Pathogens interfere with cellular cholesterol metabolism in order to support their lifecycle. Such interference may cause diseases not usually associated with infection, like cardiovascular disease. Restoring normal cholesterol metabolism may help treating infection and its metabolic consequences. We will investigate molecular, cellular and physiological mechanisms of interaction of pathogens with cholesterol metabolism to find a key point that can be targeted for therapeutic intervention.
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.