Novel Approaches To Control Mast Cell Function In Allergic Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$723,447.00
Summary
Allergic disorders are a major health problem. Driven by mast cells, the underlying inflammation is exacerbated by the ‘?c family’ of cytokines acting on the surface of these cells. We aim to characterise the ‘mast cell-?c axis’ with the view to developing new therapies based on our ?c receptors blocking antibodies. This path of discovery-mechanism-translation seeks to recapitulate our previous success of taking a related antibody to Phase II clinical trials to treat patients with leukaemia.
Potent Small Molecule Modulators Of A Complement Protein In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$689,428.00
Summary
We have invented powerful new compounds that act on the cell surface and regulate inflammation. We plan to (1) fine-tune our small molecules for optimal activity on different kinds of immune cells; (2) understand mechanisms by which the compounds affect cellular inflammatory responses; (3) evaluate the compounds as potential treatments in rodent models of inflammatory diseases implicated from cell studies. This study is anticipated to lead to clinical studies for a new kind of drug treatment.
Downsizing A Human Protein To Modulate Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$516,793.00
Summary
We have discovered how to downsize a human protein to very small molecules with the same activities and potencies. Small changes enable the compounds to powerfully block the actions of the protein. These small molecules are very stable in blood, whereas the protein deactivates in minutes. This project will develop the small molecules into experimental drugs and test them in human cells and proteins, and in rats to evaluate their potential for treating human inflammatory diseases.
Preventing Blindness: Blocking TGF¤-induced EMT And Cataract Development
Funder
National Health and Medical Research Council
Funding Amount
$343,824.00
Summary
Cataract, the loss of transparency of the eye lens, is a major cause of blindness. We have identified molecules in the lens important for maintenance of its transparency and plan to characterise their effectiveness in preventing cataract formation.
Suppressor Of Cytokine Signalling (SOCS4) Is A Critical Regulator Of The Anti-viral Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$616,912.00
Summary
The SOCS proteins are negative regulators of cytokine signalling and immune cell development and function. SOCS4 is the last remaining SOCS protein for which there is no described function or intracellular target. We intend to use well-defined acute and chronic viral disease models, and investigate the role of SOCS4 in infection in order to unravel its function. We will also search for its binding partners and intracellular targets, and determine the signalling pathways regulated by SOCS4.
Molecular Characterisation Of A New Survival Pathway In Haematopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$571,631.00
Summary
It is critical for normal health that cells regulate their responses to changes in the the extracellular environment. Receptors on the cell surface are triggered by specific proteins called cytokines, and relay information to the cell interior. These messages include signaling whether cells should survive and proliferate. Inappropriate activation of signals for survival and proliferation is a hallmark of cancer. We are investigating a new survival signal and how this contributes to the survival ....It is critical for normal health that cells regulate their responses to changes in the the extracellular environment. Receptors on the cell surface are triggered by specific proteins called cytokines, and relay information to the cell interior. These messages include signaling whether cells should survive and proliferate. Inappropriate activation of signals for survival and proliferation is a hallmark of cancer. We are investigating a new survival signal and how this contributes to the survival of normal cells and to diseases such as leukaemia.Read moreRead less
Phospholipase Cbeta 1b, A Target To Limit Atrial Dilatation
Funder
National Health and Medical Research Council
Funding Amount
$544,847.00
Summary
We have identified a heart specific protein that is involved in perpetuating dilatation of the upper chambers of the heart and thereby contributing to cardiac disease. Inhibitors of this protein provide a suitable target for therapy to limit heart disease. The current studies aim to test such inhibitors in vivo as proof-of-concept that such treatment effectively limits cardiac dysfunction.
Pre-clinical Assessment Of The Therapeutic Potential Of Targeting The Hippo Pathway In Muscle Wasting & Muscle-derived Cancer
Funder
National Health and Medical Research Council
Funding Amount
$621,979.00
Summary
Recent findings have identified the Hippo signalling pathway as an important regulator of processes in muscle fibres and muscle progenitor cells. This project will look at the significance of the Hippo pathway in the development of muscle wasting caused by statin administration, and in the genesis of muscle derived tumors (rhabdomyosarcoma). The studies will determine if interventions that regulate the Hippo pathway could provide new therapies for these important muscle-related diseases.
The Role Of Store-operated Calcium Entry In Neuronal Development
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Defects in brain development can manifest in a range of disorders including autism and mental retardation. The highly complex, precise network that is our nervous system forms during development. Our work will determine the role of key proteins in guiding developing neurons. Understanding the function of such proteins will improve our ability to predict the outcome caused by mutations in these proteins, in the developing foetus.
Fzd receptors are often upregulated in gastric cancer, and recent studies have shown that targeting these receptors has be effective at reducing cancer cell growth in other cancers including prostate and breast. This project will use cutting edge technology to firstly determine the specific requirement for Fzd receptors during gastric cancer and then determine the therapeutic benefit of using an antibody to target these receptors in mouse models and human gastric cancer cells.