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
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
The Role Of Hox Genes In Myeloid Cell Development And Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$591,286.00
Summary
The transformation of normal white blood cells into leukaemic cells occurs as a result of changes to the genes of those cells. These changes are often characteristic of particular cancers and carry diagnostic and prognostic significance. This work will determine how critical some of the typical genetic changes of leukaemia are to the occurrence and persistence of cancer. Importantly, we will determine whether targeting these changes can provide new and effective approaches to treatment.
Dissecting The Role Of The IL-3 Receptor Alpha Subunit And Beta-catenin In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$583,312.00
Summary
Leukaemia is a devastating form of blood cancer affecting both young and old. We aim to understand the mechanisms of uncontrolled cell growth associated with acute myeloid leukaemia. We focus on the role of key growth regulators that are abnormally active in the critical leukaemia stem cells. Understanding the biological and molecular properties of these cells is of considerable importance for development of the next generation of leukaemia therapies.
Treating and preventing painful fractures could be improved by strengthening cortical bone – the hard outer shell of all bones in the skeleton. We don’t know how cortical bone forms, but if we did, we could improve its strength. We have found that a brain-like network of cells inside the skeleton, called osteocytes, use a specific signal, called SOCS3, to make strong cortical bone. This study will find out how SOCS3 works and find new ways to make cortical bone strong and healthy.
Immune Balance-regulating Interleukins As Targets For Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
The immune balance is crucial to human health. Interleukins are a group of proteins secreted by immune cells to mediate their communication. They tune up or down immune responses, thus as attractive targets for immunotherapy to restore the immune balance to treat autoimmune diseases, allergies and infections. This fellowship will support translational research to develop Interleukin-2 (IL-2) and IL-21-based novel immunotherapies for autoimmune disease, infection and allergy.