Factors Controlling Lipid Accumulation In Non-adipose Tissues
Funder
National Health and Medical Research Council
Funding Amount
$463,500.00
Summary
The fat cells of the body are designed to store excess fuel for use when supply from the diet is low, or in situations like exercise, demand is high. Fat also accumulates to some extent in the cells of other tissues types, but in some people the accumulation is excessive. This can have a number of serious effects. In the liver and muscle it can interfere with the ability of insulin to properly regulate the amount of glucose present in the blood, contributing to the development of diabetes. In th ....The fat cells of the body are designed to store excess fuel for use when supply from the diet is low, or in situations like exercise, demand is high. Fat also accumulates to some extent in the cells of other tissues types, but in some people the accumulation is excessive. This can have a number of serious effects. In the liver and muscle it can interfere with the ability of insulin to properly regulate the amount of glucose present in the blood, contributing to the development of diabetes. In the liver, fat accumulation can also lead to cirrhosis and liver failure. Cardiovascular complications, resulting in premature death, are also likely. However despite these devastating consequences it is not clear what the underlying cause of the over-accumulation of fat is not known. In this project we will investigate in detail several aspects of fat metabolism that we think are important in controlling how tissues take up fat from the circulation and whether it is subsequently stored or burnt for energy. We will study the amount of fat that is taken up by different tissues of the body under a range of conditions including fed, and short- and long-term fasting. We will also use drugs to inhibit or promote the amount of fat that is burnt, to see if this changes the rate at which fat is taken up by different tissues. In addition we will accelerate, by genetic manipulation, the rate at which some key enzymes of fat metabolism are produced, to determine their effect on the amount of fat that is stored by different tissue types. Our aim is to determine the metabolic processes that influence fat accumulation in those adversely affected tissues such as liver, heart and skeletal muscle. The identification of the most important processes will contribute significantly to the targeting of therapies aimed at preventing excess fat accumulation and its associated diseases.Read moreRead less
Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their ....Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their etiology, both forms result in an inability of the body to control blood sugar levels. Beta cells release the hormone insulin, which regulates blood sugar levels. Current knowledge suggests that a loss of beta cell mass is important for both diseases. For type I diabetes the beta cells are destroyed by the immune system. Though for type 2 diabetes the causes are less clear, it is apparent that the beta cells are dying. Our research is focused on understanding the molecular pathways that control beta cell survival and regulate their death. Such knowledge would help us understand the complex processes leading to the development of diabetes. Furthermore, we could use this knowledge in the design of genetic engineering strategies to create 'death-defying' beta cells, as a potential therapeutic strategy for the treatment of diabetes.Read moreRead less
Elimination of the transplant waiting list is the ultimate goal of research into pigto-human xenotransplantation. The prospect of success has been improved recently by refinements in technology used to introduce genetic modifications in the pig, although the genes that will need to be expressed or deleted are still undecided. What is clear is that intravascular thrombosis, a critical mediator of rejection of pig xenografts, must be overcome. This project aims to investigate the use of anticoagul ....Elimination of the transplant waiting list is the ultimate goal of research into pigto-human xenotransplantation. The prospect of success has been improved recently by refinements in technology used to introduce genetic modifications in the pig, although the genes that will need to be expressed or deleted are still undecided. What is clear is that intravascular thrombosis, a critical mediator of rejection of pig xenografts, must be overcome. This project aims to investigate the use of anticoagulant gene expression to prevent intravascular thrombosis associated with xenograft rejection.Read moreRead less
A New Mechanism Of Tissue Fibrosis - A Small Peptide Regulator Of The TGF-beta1/Smad Pathway
Funder
National Health and Medical Research Council
Funding Amount
$768,757.00
Summary
Progressive scarring, or fibrosis, of organs leads to their loss of function. Fibrotic diseases are devastating to both the individual and our community and we lack effective therapies. We have identified a small protein, named SPRF, which represents a new mechanism in tissue fibrosis. These studies will examine the role of the SRPF protein in models of kidney, heart and lung fibrosis and its underlying mechanism of action. We will also test a therapy based on inhibiting SPRF function.
Antiphospholipid Syndrome Related Thrombosis: Understanding The Disease Pathogenic Mechanisms Is The Key To Better Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$607,497.00
Summary
Patients with the Antiphospholipid Syndrome develop thrombosis at a young age. It requires long-term treatment with blood thinning medications, which have risks of severe bleeding. Methods are needed to decide which patients require long term treatment, avoiding unnecessary treatment in low risk patients. Such methods do not currently exist. In this study we explore how useful two novel assays developed by us are in identifying which of these patients are at high risk of thrombosis.