Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue 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 tissue 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 (see http:--www.imb.uq.edu.au-groups-james-glut4 for an animated description of this process). 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
The Regulation Of PI 3-kinase Second Messenger Molecules, PtdIns(3,4)P2 And PtdIns 3-P.
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
Cells respond to the external environment, hormones, and growth factors by generating messages inside the cell that send a signal to the nucleus that stimulates cell growth. One such signalling network is that produced by membrane lipids known as phosphoinositides. Enzymes that produce these signals are known as kinases. There has been considerable interest in the PI 3-kinase as the signals generated by this enzyme are increased in many human cancers. Inherited cancer syndromes have been describ ....Cells respond to the external environment, hormones, and growth factors by generating messages inside the cell that send a signal to the nucleus that stimulates cell growth. One such signalling network is that produced by membrane lipids known as phosphoinositides. Enzymes that produce these signals are known as kinases. There has been considerable interest in the PI 3-kinase as the signals generated by this enzyme are increased in many human cancers. Inherited cancer syndromes have been described that have lost the ability to switch off PI 3-kinase signals. The current project aims to investigate a recently identified enzyme called the 4-phosphatase that has the ability to terminate PI 3-kinase signals. Recent studies have shown this enzyme regulates cell growth. In addition key experiments have shown the enzyme is important as it may regulate certain strains of bacterial infection. This research proposal aims to investigate how the enzyme works to regulate these growth promoting signals. This may help us develop novel therapeutic strategies to control cell growth.Read moreRead less
Prof Parton is a cell biologist studying how the plasma membrane functions in health and in disease. These studies have provided new insights into potential vehicles that can be used to introduce therapeutic agents into cells.
The regulated movement of membrane receptors and ligands between the cell surface and intracellular compartments is vital to many cellular operations, including communication between cells and their environment. However, the molecular details of these sorting events remain poorly defined. Determination of the mechanisms that control the cellular distribution of receptors is critical for understanding normal cellular processes and in pathological processes like tumorigenesis.
Characterisation Of A New Family Of Proteins Involved In Cell Signalling, RNA Metabolism And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$200,880.00
Summary
We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of th ....We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of these RNA-binding proteins have been identified. We have shown that the novel protein discovered in our laboratory is perturbed in cancer and we are interested in characterising its putative role in cancer. The results established in our laboratory so far would indicate that generally, G3BP-2 is expressed in normal tissue and it expression changes in some cancers studied so far. Considering that G3BP-2 lies in a pathway known to be involved in cancer progression it is important to understand what effects the inappropriate expression of G3BP-2 may have on cancer progression and survival. This project is designed to characterise what signals the cell uses to control these proteins and in turn which genes these may effect. In this way we may be able to determine how external signals may effect tumour progression and on what genes this influence is expressed. It would be hoped that this project would increase our understanding of cancer and potentially lead to new diagnostic reagents and therapies in the treatment of cancer.Read moreRead less