Following a meal glucose circulates in the blood and is taken up into cells via movement of an intracellular glucose transporter from the inside of the cell to fuse with the cell membrane and subsequent transfer of the glucose into the cell. This process is triggered by insulin. One of the commonest diseases resulting from a failure of this cellular process is diabetes. A common form of diabetes which occurs in many adults in Australia results from insulin resistance, whereby the effects of insu ....Following a meal glucose circulates in the blood and is taken up into cells via movement of an intracellular glucose transporter from the inside of the cell to fuse with the cell membrane and subsequent transfer of the glucose into the cell. This process is triggered by insulin. One of the commonest diseases resulting from a failure of this cellular process is diabetes. A common form of diabetes which occurs in many adults in Australia results from insulin resistance, whereby the effects of insulin are diminished and cells become increasingly unable to uptake glucose. Recent studies have demonstrated that a novel enzyme known as SHIP-2 may play a role in regulating insulin action in cells. Deletion of SHIP-2 in mice results in these animals have increased sensitivity to insulin, low blood glucose levels, and a greatly enhanced ability to take up glucose in cells in response to low dose insulin. Our laboratory has been working on the cellular mechanisms regulating SHIP-2 function. We have recently revealed the intracellular location of SHIP-2 and also demonstrated how SHIP-2 is localized in the cell. These studies have shown that SHIP-2, via interactions with other proteins, regulates the actin cytoskeleton immediately beneath the cell membrane and this may be a mechanism for facilitating cellular glucose uptake. This research proposal aims to determine how SHIP-2 facilitates glucose uptake into cells. We will make cell lines and transgenic animals which express high levels of this enzyme and determine the functional consequences on insulin stimulated glucose uptake. Collectively these studies in the long term may facilitate better treatment strategies for diabetic patients.Read moreRead less
Identification And Characterization Of Novel PI3-kinase Signal Transducing Elements In Platelets
Funder
National Health and Medical Research Council
Funding Amount
$457,500.00
Summary
Platelets play an important role in blood clotting and blood vessel repair. Upon vessel injury, platelets rapidly adhere to the site of damage where they undergo dramatic shape change to spread over the site of injury. Activation and regulation of these processes relies on a complex network of signal transduction processes, involving the integration of multiple receptors and pathways. One pathway demonstrated to play a role in regulating platelet responses is the enzyme phosphatidylinositol 3-ki ....Platelets play an important role in blood clotting and blood vessel repair. Upon vessel injury, platelets rapidly adhere to the site of damage where they undergo dramatic shape change to spread over the site of injury. Activation and regulation of these processes relies on a complex network of signal transduction processes, involving the integration of multiple receptors and pathways. One pathway demonstrated to play a role in regulating platelet responses is the enzyme phosphatidylinositol 3-kinase (PI3-kinase) and its lipid products PtdIns(3,4,5)P3 and PtdIns(3,4)P2. However, very little is known about exactly how PI3-kinase and its products regulate the platelet responses. Our research studies aim to gain a deeper understanding into the molecular mechanisms of PI3-kinase signal transduction in platelets, through the identification and characterization of novel platelet proteins that bind to PI3-kinase lipid products, and to define what role these proteins play in platelet PI3-kinase dependent responses.Read moreRead less
Structural Studies Of The Jak And Abl Kinases: A Prerequisite For Drug Design
Funder
National Health and Medical Research Council
Funding Amount
$360,965.00
Summary
Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune related disorders. This fellowship aims to develop more potent kinase inhibitors of a number of PTKs using Cytopia’s drug discovery capability coupled with the X-ray crystallography expertise within Monash University. This innovative approach will permit a rational structure-based drug discovery platform to be established and will lead to the creation of a portfolio ....Protein tyrosine kinases (PTK) are a large, pivotal family of signalling molecules implicated in diseases such as cancer and immune related disorders. This fellowship aims to develop more potent kinase inhibitors of a number of PTKs using Cytopia’s drug discovery capability coupled with the X-ray crystallography expertise within Monash University. This innovative approach will permit a rational structure-based drug discovery platform to be established and will lead to the creation of a portfolio of phase I therapeutics, which will be of substantial benefit in the medical health area.Read moreRead less
Identification And Characterization Of Substrates Of Tyrosine Kinases Involved In Hematopoiesis And Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$241,527.00
Summary
The development and maintenance of tissues in mammals are tightly controlled and complex processes involving the growth, maturation and survival of vast numbers of cells of various types. In cancer, the cell's capacity to faithfully regulate these processes is diminished or lost. Many of the proteins that are essential for growth control are produced by an important class of genes called proto-oncogenes; literally, the prototypes of cancer-causing genes. Naturally occurring mutations in these ge ....The development and maintenance of tissues in mammals are tightly controlled and complex processes involving the growth, maturation and survival of vast numbers of cells of various types. In cancer, the cell's capacity to faithfully regulate these processes is diminished or lost. Many of the proteins that are essential for growth control are produced by an important class of genes called proto-oncogenes; literally, the prototypes of cancer-causing genes. Naturally occurring mutations in these genes have been identified in man and are likely to play a major role in the initiation and progression of distinct human malignancies. A significant number of proto-oncogenes are enzymes called protein tyrosine kinases (PTKs). Research has shown that the function of PTKs is to relay growth signals or other regulatory signals from the outer surface of the cell to specific target proteins inside the cell. These target proteins are needed to relay the signal to other target molecules and so on. This highly ordered process, involving a specific sequence of proteins, ensures that cells respond appropriately to a given signal. Our research focuses on identifying and studying the immediate targets of PTKs with the broad aim of understanding how PTKs control growth in normal and cancerous cells. We have recently developed a method that has enabled us to identify a new protein that may regulate the growth of blood cells. The research proposed here aims to extend our preliminary observations showing that the growth of specific types of blood cells is inhibited by this protein. We also plan to search for new targets of a PTK that is involved in leukemia. The findings of this research will provide important insight into how blood cells are regulated in health and disease.Read moreRead less