Modulating Neuronal Secretion By The PI3-kinase Pathway
Funder
National Health and Medical Research Council
Funding Amount
$516,855.00
Summary
Neuronal communication relies on the process of exocytosis by which neurons release neurotransmitter. Exocytosis is critical for the simplest reflex movement to complex tasks such as learning and memory, and is altered in several neurodegenerative pathologies. We will investigate how certain lipids control exocytosis. This research is important for understanding how neurons communicate in health and disease and is relevant to other processes such as insulin release in diabetes.
Structural Characterisation Of SNARE Protein Complexes Involved In Insulin-regulated Glucose Transport
Funder
National Health and Medical Research Council
Funding Amount
$320,803.00
Summary
Insulin-regulated glucose transportation is defective in type 2 diabetes, a disease that is a major health problem worldwide and in some cases can lead to death. The aim of this work is to investigate the molecular structure and function of proteins critical to the transportation and delivery of glucose to muscle and fat cells, which will lead to the validation of new therapeutic targets and the development of new treatments for diabetes.
Neuronal communication relies on the process of exocytosis by which neurons release a neurotransmitter. Exocytosis is critical for the simplest muscle movement to complex tasks such as learning and memory, and is altered in several neurodegenerative pathologies. We will investigate how the protein Munc18 controls exocytosis. This research will be important for understanding how neurons communicate in health and disease and will be relevant to other processes such as insulin release in diabetes.
Macrophages are important cells at the front-line of immunity where one of their main roles is to release anti-bacterial proteins. We will study the macrophage molecules, subcellular organelles and pathways that help to release these proteins to kill bacteria and fight infection. Our studies will identify new cellular targets for boosting immunity and treating inherited diseases with defective macrophage function.
Structural Studies On SNARE Proteins Involved In Insulin Action
Funder
National Health and Medical Research Council
Funding Amount
$308,263.00
Summary
Diabetes mellitus, a disease characterised by high blood glucose levels, is caused by a relative or absolute deficiency in the activity of insulin. The blood-glucose lowering action of insulin is a result of its ability to stimulate glucose uptake by fat and muscle cells. A major goal of Professor James' laboratory is to identify molecules that are involved in this insulin-regulated uptake of glucose. Professor James has identified and characterised the glucose transporter, GLUT4, a protein that ....Diabetes mellitus, a disease characterised by high blood glucose levels, is caused by a relative or absolute deficiency in the activity of insulin. The blood-glucose lowering action of insulin is a result of its ability to stimulate glucose uptake by fat and muscle cells. A major goal of Professor James' laboratory is to identify molecules that are involved in this insulin-regulated uptake of glucose. Professor James has identified and characterised the glucose transporter, GLUT4, a protein that is normally stored inside muscle and fat cells. In response to insulin stimulation, GLUT4 moves to the cell surface where it functions to transport glucose into the cell. Over the past 5 years Professor James laboratory has, in conjunction with other groups, discovered several key proteins that are involved in the insulin-regulated movement of GLUT4 within the cell. We plan to exploit the therapeutic potential of this biological system by obtaining high resolution three dimensional structures of these key proteins. The resulting structural information will allow us to develop compounds that modify the function of these key proteins. Such compounds could prove useful as novel therapeutic agents in the treatment of diabetes. The purpose of this proposal is to begin to implement this goal. By combining the knowledge and reagents coming out of the work on insulin-regulated glucose transport in Professor James' laboratory with the molecular and structural biology expertise in Dr Martin's, Dr Halliday's and Prof Craik's laboratories we are in a unique position to achieve this highly significant goal.Read moreRead less
The Role Of Endothelial Lipase In High Density Lipoprotein Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$130,550.00
Summary
Atherosclerosis is a major cause of death and disability in Australia. A high level of blood cholesterol increases the risk of developing atherosclerosis. This increase in risk is caused by the cholesterol that is carried in low density lipoproteins (LDL). However, not all cholesterol is bad. A proportion of the cholesterol in blood is carried in high density lipoproteins (HDL), which are powerful protectors against atherosclerosis. As not all HDL protect equally well against atherosclerosis, it ....Atherosclerosis is a major cause of death and disability in Australia. A high level of blood cholesterol increases the risk of developing atherosclerosis. This increase in risk is caused by the cholesterol that is carried in low density lipoproteins (LDL). However, not all cholesterol is bad. A proportion of the cholesterol in blood is carried in high density lipoproteins (HDL), which are powerful protectors against atherosclerosis. As not all HDL protect equally well against atherosclerosis, it is important to know how blood levels of HDL are regulated. In 1999 a new enzyme called endothelial lipase was discovered. Endothelial lipase dramatically decreases HDL levels in mice. The reason why this happens is not known. The main aims of this project are to work out how endothelial lipase decreases HDL levels and whether it decreases the levels of all HDL equally or whether it preferentially decreases the levels of certain types of HDL. The outcome of this project will establish how endothelial lipase affects the ability of HDL to protect against atherosclerosis in humans.Read moreRead less
Deciphering The Molecular Basis Of SM Regulation Of Exocytosis
Funder
National Health and Medical Research Council
Funding Amount
$515,564.00
Summary
Diabetes, obesity, heart disease and physical inactivity are major and escalating health problems within western societies. These problems are all linked to, or aggravate, the condition known as insulin resistance. Insulin resistance occurs when normal levels of insulin are insufficient to remove glucose from the blood. In the normal situation, insulin regulates glucose uptake into muscle and fat cells by stimulating the movement of a glucose transport protein from inside the cell to the cell su ....Diabetes, obesity, heart disease and physical inactivity are major and escalating health problems within western societies. These problems are all linked to, or aggravate, the condition known as insulin resistance. Insulin resistance occurs when normal levels of insulin are insufficient to remove glucose from the blood. In the normal situation, insulin regulates glucose uptake into muscle and fat cells by stimulating the movement of a glucose transport protein from inside the cell to the cell surface. The trafficking of this protein is somehow disrupted in insulin resistance. The purpose of this research is to follow up our exciting preliminary results on this system to shed light on the molecular processes that regulate the trafficking of the glucose transporter. Information resulting from our studies will lead to a better understanding of insulin-stimulated glucose transport and may also unravel the details of a related cellular secretion system that regulates neurotransmission. Our hope is that by understanding at the molecular level how cells regulate secretion, we can in the future develop therapeutics to counteract many of today s major health problems.Read moreRead less