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.
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.
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
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.
Lipid Metabolism In The Hypothalamus: Implications For Obesity And Diabetes Development
Funder
National Health and Medical Research Council
Funding Amount
$592,915.00
Summary
Obesity is defined by excessive fat storage and defective lipid metabolism, not only in adipose tissue, but also in most tissues throughout the body. Obesity-induced changes in lipid metabolism extends to the brain and is associated with impaired cognitive function. This work aims to determine how obesity affects neurons in the key feeding centres of the brain, and whether excessive lipid storage in neurons induces changes in body weight regulation and metabolism.
The Role Of Adipose Tissue Cholesterol In Metabolic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$888,340.00
Summary
Adipose tissue is important for human health. Adipose tissue can normally store a significant amount of cholesterol. Impairment of this function will cause a number of devastating diseases such as heart disease and stroke. The proposed work will help understand how adipose tissue store cholesterol. Results from this work may lead to novel therapeutic strategies against obesity and heart disease.
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.