Molecular And Functional Characterisation Of Cell Surface Microdomains
Funder
National Health and Medical Research Council
Funding Amount
$4,803,731.00
Summary
This research program aims to gain a detailed understanding of the organisation of the cell surface at the molecular level. The cell surface is organised into domains with distinct functions. Visualisation of these domains, identifying their important components, and understanding how they form and function will have huge importance for therapeutic strategies aimed at combating the changes associated with cell transformation in cancer and in other human diseases such as muscular dystrophy.
Regulation Of Signal Transduction By Cbl: Investigation Of Effects On The Cytoskeleton, Cell Adhesion And Cell Motility
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
Changes in cell adhesion and motility have been implicated in a wide range of human pathologies (e.g. immune, reproductive, mental, and cancerous disorders) . Cell adhesion and motility are tightly regulated by a group of proteins known as Rho-GTPases. Novel pharmacological agents that target signalling by Rho-GTPases have been demonstrated to profoundly affect tumour metastasis, as well as central nervous system regeneration following injury. Further exploitation of Rho-GTPase signal modulation ....Changes in cell adhesion and motility have been implicated in a wide range of human pathologies (e.g. immune, reproductive, mental, and cancerous disorders) . Cell adhesion and motility are tightly regulated by a group of proteins known as Rho-GTPases. Novel pharmacological agents that target signalling by Rho-GTPases have been demonstrated to profoundly affect tumour metastasis, as well as central nervous system regeneration following injury. Further exploitation of Rho-GTPase signal modulation, by detailed studies of the molecular mechanisms involved, could lead to significant advances in medical sciences. In particular, treatment of cancer and spinal injuries are likely to benefit from further development of Rho-signalling research.Read moreRead less
Investigating The Physiological And Biochemical Role Of SOCS5 In The Immune System
Funder
National Health and Medical Research Council
Funding Amount
$405,940.00
Summary
Asthma affects millions of people worldwide and is a complex inflammatory disease of the lung. Asthma manifests as recurrent episodes of wheezing, breathlessness, chest tightening, and coughing. Three key proteins called; interleukin 4 (IL-4), interleukin 13 (IL-13) and interleukin 5 (IL-5) are produced by a subset of white blood cells (T helper cells; Th2) and are thought to be responsible for the asthma response. Normally these proteins act to coordinate the body s immune defence against paras ....Asthma affects millions of people worldwide and is a complex inflammatory disease of the lung. Asthma manifests as recurrent episodes of wheezing, breathlessness, chest tightening, and coughing. Three key proteins called; interleukin 4 (IL-4), interleukin 13 (IL-13) and interleukin 5 (IL-5) are produced by a subset of white blood cells (T helper cells; Th2) and are thought to be responsible for the asthma response. Normally these proteins act to coordinate the body s immune defence against parasite infection. In other words, asthma is thought to arise through inappropriate IL-4 and IL-13 activity in the absence of a parasite infection. Extra IL-13 is commonly found in the lungs of asthmatics and is thought to help trigger asthma attacks. IL-13 is a validated target for drugs that could be used in the treatment of asthma. The SOCS genes were discovered in our laboratory and by genetically deleting the genes in mice we have demonstrated a critical role for SOCS1, SOCS2 and SOCS3 in regulating the immune response and the action of growth hormone. My hypothesis is that SOCS5 is an important physiologic regulator of the asthma response. This proposal will investigate the basic biochemical processes underlying the regulation of IL-4 and IL-13 action and the relationship to development of asthma and immune disease. I plan to induce asthma attacks in mice that lack the genes for SOCS4 and SOCS5. If the severity of the attacks is greater in the absence of these proteins this will indicate that SOCS4 and-or SOCS5 are important negative regulators of IL-4 and IL-13. This has the potential to open up a completely new strategy for the development of drugs that could be used in the prevention and treatment of asthma.Read moreRead less
Molecular Determinants Of Subcellular Localisation And Function Of The Transmembrane 4 Superfamily Protein, PETA-3
Funder
National Health and Medical Research Council
Funding Amount
$322,911.00
Summary
Several years ago we identified the cell membrane protein PETA-3-CD151 based on its ability to cause activation of blood platelets, suggesting a role in thrombosis. More recently we found that the protein is present in a variety of tissues, although its distribution in those tissues is often restricted. It is abundant in a variety of cancer cells, and is present on tissue mast cells that mediate allergic reactions. PETA-3-CD151 forms complexes with molecules (integrins) that are associated with ....Several years ago we identified the cell membrane protein PETA-3-CD151 based on its ability to cause activation of blood platelets, suggesting a role in thrombosis. More recently we found that the protein is present in a variety of tissues, although its distribution in those tissues is often restricted. It is abundant in a variety of cancer cells, and is present on tissue mast cells that mediate allergic reactions. PETA-3-CD151 forms complexes with molecules (integrins) that are associated with cell adhesion and migration, and antibodies to this protein inhibit cell movement. Thus PETA-3-CD151 appears to be involved in cellular interactions that are critical for normal tissue development and function, and may be involved in several disease processes including cancer invasion and metastasis. The molecular basis of PETA-3-CD151 function is not understood and is the focus of this application.Read moreRead less
Development and Characterization of Chemokine Receptor Mimics. The proposed research will provide important fundamental insights into the molecular events underlying inflammatory diseases and cancer metastasis. The innovative nature of the research and the significance of the results will enhance Australia's international research standing. Moreover, the insights gained from this work will contribute to the development of therapies that will ultimately enhance the quality of life for Australia ....Development and Characterization of Chemokine Receptor Mimics. The proposed research will provide important fundamental insights into the molecular events underlying inflammatory diseases and cancer metastasis. The innovative nature of the research and the significance of the results will enhance Australia's international research standing. Moreover, the insights gained from this work will contribute to the development of therapies that will ultimately enhance the quality of life for Australians.Read moreRead less
C-Kit Signalling And Cellular Responses In Haemopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$731,115.00
Summary
Growth factors acting on cell surface receptors activate multiple intracellular signalling pathways that regulate cellular growth and function. Mutations in the genes that code for these receptors or their downstream signalling pathways contribute to many human cancers. The contributions of different signalling pathways linked to these receptors to the various cellular responses (growth, maturation, functional activation) are not understood. In this project we aim to use cell and molecular biolo ....Growth factors acting on cell surface receptors activate multiple intracellular signalling pathways that regulate cellular growth and function. Mutations in the genes that code for these receptors or their downstream signalling pathways contribute to many human cancers. The contributions of different signalling pathways linked to these receptors to the various cellular responses (growth, maturation, functional activation) are not understood. In this project we aim to use cell and molecular biology approaches to determine the role of different signalling pathways in cellular responses mediated by the growth factor receptor c-Kit. The c-Kit receptor has essential functions in blood cell development, skin and hair pigmentation, gut function and the reproductive system. It is also essential for the development and function of mast cells which trigger allergic responses such as asthma and eczema. Mutant forms of the receptor have been identified in certain leukaemias and colon cancers. Many new drugs that target specific intracellular signalling pathways have recently been developed and are beginning to be evaluated in clinical trials. Better understanding of how individual pathways contribute to the function of c-Kit and other receptors is essential for optimal use of these new drugs. For example, it may enable the choice of drugs to block c-Kit dependent cancer cell growth or allergic reactions without affecting the growth of normal blood cells.Read moreRead less