Analysis Of Intracellular Signalling And Biological Activities Of The GM-CSF Receptor Family Using Constitutive Mutants
Funder
National Health and Medical Research Council
Funding Amount
$505,699.00
Summary
The cytokines GM-CSF, IL-3 and IL-5 stimulate the growth and actions of a wide range of blood cells. Each binds to a receptor on the cell surface which then triggers the generation of a number of signals inside the cell; it is these signals that are responsible for the cytokine?s actions. We have previously generated a panel of constitutive mutant forms of the beta subunit which is shared by the GM-CSF, IL-3 and IL-5 receptors. These constitutive mutants trigger signals even in the absence of th ....The cytokines GM-CSF, IL-3 and IL-5 stimulate the growth and actions of a wide range of blood cells. Each binds to a receptor on the cell surface which then triggers the generation of a number of signals inside the cell; it is these signals that are responsible for the cytokine?s actions. We have previously generated a panel of constitutive mutant forms of the beta subunit which is shared by the GM-CSF, IL-3 and IL-5 receptors. These constitutive mutants trigger signals even in the absence of the cytokine; importantly, the different mutants appear to trigger only a subset of the signals generated by the normal receptor. The aim of this project is to use our panel of constitutive beta subunit mutants to determine how the GM-CSF, IL-3 and IL-5 receptors generate signals inside the cell and how these signals lead to the various biological actions of the receptors on blood cell growth and maturation. Findings from this research will be relevant to the understanding and treatment of diseases which involve abnormal growth or function of blood cells such as leukaemia and inflammatory diseases.Read moreRead less
Development Of An Interleukin-11 Signalling Antagonist
Funder
National Health and Medical Research Council
Funding Amount
$625,830.00
Summary
Interleukin (IL)-11 is a soluble signalling molecule that is associated with many types of cancer. We have recently discovered that IL-11 signalling is a novel and tractable therapeutic target for the treatment of colon cancer. The aims of this proposal are to understand the structural details of IL-11 signalling. We will use this information to develop new and improved therapeutics for colon cancer.
Interleukin-3 Receptor Signaling Is A Driver Of Myeloid Leukaemia And A Significant Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$601,966.00
Summary
Acute Myeloid Leukaemia (AML) is an aggressive blood cancer. There are many types of AML, but overall, less than half of those with AML are cured. This project evaluates how certain molecules on the surfaces of leukaemic cells keep those cells alive and growing. We are also testing new ways to block these molecules and so provide new therapies for this cancer.
A Novel Class Of Negative Regulators Of Interleukin-6 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$626,950.00
Summary
Cytokines are protein messengers that activate the immune system to fight infections. When they are too active they cause inflammation and autoimmune diseases so their activity needs to be tightly controlled. We have discovered a new family of regulators (the MARCH proteins) that inhibit cytokine activity by routing cytokine receptors for destruction. We aim to understand how this process works in detail and the role of MARCH proteins in vivo in ameliorating autoimmune diseases.
Determining The Structure Of A Soluble Cytokine Receptor Complex
Funder
National Health and Medical Research Council
Funding Amount
$509,017.00
Summary
There is a pressing need to develop improved therapeutics to treat many forms of cancer and respiratory diseases. This proposal concerns the biochemical investigation of a group of protein hormones and their associated receptors that are implicated in blood cell cancers and for which current treatments are only partly effective . Our work will focus on determining the 3-dimensional shape and function of this group of proteins in complex with one another which will provide us with an understandin ....There is a pressing need to develop improved therapeutics to treat many forms of cancer and respiratory diseases. This proposal concerns the biochemical investigation of a group of protein hormones and their associated receptors that are implicated in blood cell cancers and for which current treatments are only partly effective . Our work will focus on determining the 3-dimensional shape and function of this group of proteins in complex with one another which will provide us with an understanding of how these proteins communicate with one another. This information may provide a basis for the design of new drugs that can specifically block the activity of these protein hormones, thereby providing new treatment possibilities for these blood cell cancers.Read moreRead less
Elucidating The Molecular Regulation Of Gp130 Complex Signalling In Lipid And Glucose Metabolism.
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Overnutrition promotes obesity, which greatly increases the risk of type 2 diabetes and cardiovascular disease. We have provided evidence that activation of gp130 signalling may enhance insulin action and fatty acid oxidation in metabolically active tissues. My research proposal aims to elucidate the molecular regulation of gp130 complex signalling in lipid and glucose metabolism in important metabolic tissues.