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.
Control Of SNARE-mediated Granule Fusion In Mast Cells
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Asthma is an allergic disease affecting two million Australians. A major player in asthma is the mast cell which releases histamine when the cell is stimulated by antigen. The process by which histamine is released involves fusion of cytoplasmic granules containing the histamine with the cell surface membrane. The mechanism of this fusion process appears to be different in mast cells compared with other cells studied, raising the possibility that release of histamine, and hence the acute allergi ....Asthma is an allergic disease affecting two million Australians. A major player in asthma is the mast cell which releases histamine when the cell is stimulated by antigen. The process by which histamine is released involves fusion of cytoplasmic granules containing the histamine with the cell surface membrane. The mechanism of this fusion process appears to be different in mast cells compared with other cells studied, raising the possibility that release of histamine, and hence the acute allergic response, could be controlled if more were understood about the fusion process. This project aims to define the mechanism by which granules dock and then fuse with the cell surface. These are the two apects most likely to be unique in mast cells.Read moreRead less
The neuronal synapse is very tightly regulated by proteins that control both the timing and the amount of neurotransmitter release and neuronal stimulation. Defects in this synaptic signal are linked to diseases including epilepsy, autism and dementia. In this study we will determine the molecular details of how proteins called SNAREs control neurotransmission in the human brain.
Obesity and diabetes are increasing in our community at an alarming rate. When one considers that Diabetes is a major cause of heart disease, stroke and kidney disease these diseases represent one of the most threatening for the future health of our nation. At the heart of these diseases is a disorder known as insulin resistance, or the inability of insulin to function correctly. The explosion in biological outcomes over the past decade has brought us closer than ever before to solving some of t ....Obesity and diabetes are increasing in our community at an alarming rate. When one considers that Diabetes is a major cause of heart disease, stroke and kidney disease these diseases represent one of the most threatening for the future health of our nation. At the heart of these diseases is a disorder known as insulin resistance, or the inability of insulin to function correctly. The explosion in biological outcomes over the past decade has brought us closer than ever before to solving some of the key questions associated with this problem. This proposal represents an exciting step forward in this area because our recent research combined with information from our international colleagues have led us to propose a new concept concerning the mechanism of insulin action. In this proposal we have formulated a series of molecular experiments to test this hypothesis which if correct will both change the way we think about this problem and provide new prospects for therapeutic design.Read moreRead less
Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tisse to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle ....Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tisse to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle and adipose tissue by stimulating the movement of a glucose transport protein from inside the cell to the cell surface. The purpose of this proposal is to dissect the molecular mechanisms by which this glucose transporter can be held inside the cell in the absence of insulin and then allowed to be released from this site moving to the surface in the presence of insulin. Our studies over the past 5 years have brought us much closer to understanding this process in detail. The identification of the molecules responsible for this regulatory step will not only aid our understanding of this process but it will also provide a valuable target for development of therapeutic agents that can be used to combat insulin resistance.Read moreRead less
Dissection Of Insulin Regulated Phosphorylation In The Adipocyte
Funder
National Health and Medical Research Council
Funding Amount
$303,510.00
Summary
Obesity and diabetes are increasing at an alarming rate throughout the world. These diseases are part of a constellation of disorders that includes cardiovascular disease and kidney disease, which are collectively referred to as the metabolic syndrome. A disorder referred to as insulin resistance is at the heart of the metabolic syndrome. This represents the inability of insulin to function correctly in target cells like muscle and fat. In this project we are attempting to undertake a large scal ....Obesity and diabetes are increasing at an alarming rate throughout the world. These diseases are part of a constellation of disorders that includes cardiovascular disease and kidney disease, which are collectively referred to as the metabolic syndrome. A disorder referred to as insulin resistance is at the heart of the metabolic syndrome. This represents the inability of insulin to function correctly in target cells like muscle and fat. In this project we are attempting to undertake a large scale effort to understand the complex circuitry that gets turned on within cells when they become exposed to insulin. This project involves a collaboration between the Garvan Institute and the University of New South Wales Mass Spectrometry Facility allowing us to bring a combination of very sophisticated technologies to bear on this very significant health care problem. This project will provide major new insights into our understanding of insulin action yielding new possibilities for therapeutic development.Read moreRead less
Mechanism Of Action Of Sec1p-like Proteins In Membrane Trafficking.
Funder
National Health and Medical Research Council
Funding Amount
$440,250.00
Summary
One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has ....One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has developed a complex assembly line of modifications that are added to proteins in a specific order as they travel to their final destination within the cell. This necessitates the accurate passage of molecules between compartments, a process known as vesicle transport. To orchestrate the complex network of vesicular transport steps between all of the various intracellular compartments it is necessary to employ complex machinery to guide and check that these steps occur with high fidelity. The goal of our research proposal is to define the function of one of the molecules involved in this control process, the so-called Sec1p proteins. The strength of our proposal lies in the diversity of our approach. We intend to explore the molecular advantages of a relatively simple eukaryotic organism, a yeast cell, and apply the findings obtained from this cell to a more complex but highly related vesicular transport process; that of the insulin-regulated movement of a glucose transporter in mammalian fat and muscle cells. While we intend to apply our findings to the treatment of patients with diabetes, it is our ultimate goal to be able to learn more about this fundamental cell biological process so that we can apply our knowledge to understanding many different disease states.Read moreRead less