Structural Events In Insulin And IGF Signalling - A Nanodisc Approach To A Problem In Cancer, Diabetes And Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$752,403.00
Summary
Insulin and its insulin-like growth factors play a major role in three major disease states facing ageing Australians—diabetes, cancer and Alzheimer's disease. We aim to understand how these proteins send messages into cells via their so-called receptors. We will isolate the receptor molecules from cells and then image them in an advanced electron microscope to produce three-dimensional images. Our findings will have implications for the design of therapeutics targeting the above three diseases.
Conformational Change In Insulin And Type I Insulin-like Growth Factor Receptor Upon Ligand Binding
Funder
National Health and Medical Research Council
Funding Amount
$415,365.00
Summary
Insulin and insulin-like growth factors bind to receptor molecules on the surfaces of cells. The binding event results in a signal being sent into the cell to initiate in the case of insulin, uptake of glucose into the cell and, in the case of the growth factors, normal human growth. Breakdown of these processes is implicated in a number of disease states, including diabetes, cancer and Alzheimer's disease. This Project aims to decipher the receptor triggering mechanism that is responsible for g ....Insulin and insulin-like growth factors bind to receptor molecules on the surfaces of cells. The binding event results in a signal being sent into the cell to initiate in the case of insulin, uptake of glucose into the cell and, in the case of the growth factors, normal human growth. Breakdown of these processes is implicated in a number of disease states, including diabetes, cancer and Alzheimer's disease. This Project aims to decipher the receptor triggering mechanism that is responsible for getting the signal into the cell.Read moreRead less
Targeting The Insulin And Insulin-like Growth Factor Receptors In Cancer, Diabetes And Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$993,251.00
Summary
Diabetes, cancer and Alzheimer's disease are three major diseases facing Australia. This Project will investigate a common point-of-focus of these diseases, namely the interaction of insulin and the insulin-like growth factors with their receptor molecules on the cell surface. It will use recent breakthrough findings by the Chief Investigators to develop new therapeutic approaches for these diseases that could function by targeting these interactions.
Conologues: Ultra-fast-acting Therapeutic Insulins Based On Cone Snail Venom Insulin Principles
Funder
National Health and Medical Research Council
Funding Amount
$1,082,866.00
Summary
The increasing prevalence of Type 1 and Type 2 diabetes demands better treatments. Our Project is based on a fascinating discovery by our international team of CIs of a new type of insulin within marine organisms that could form the basis of a novel diabetes therapeutic. Within our Project we will exploit this discovery to develop a new class of ultra-rapid-acting therapeutic insulins.
Understanding Cell Signalling As A Basis For New Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$863,910.00
Summary
This fellowship will capitalise on my extensive expertise in determining the three-dimensional atomic structures of proteins to uncover fundamental biological mechanisms in cancer and Alzheimer’s disease as a basis for discovering new drugs to combat these devastating diseases.
Activation And Inhibition Of The Plasminogen/Plasmin System
Funder
National Health and Medical Research Council
Funding Amount
$800,663.00
Summary
Plasmin is crucial enzyme present in blood plasma that functions in clot dissolution, inflammation, tissue remodeling, and wound healing. We aim to study how this enzyme system is controlled, by studying its interaction with receptors, co-factors and inhibitors. The information we gain will help drive the development of new generation therapeutics for the fine control of plasmin function in clotting disease, bleeding and inflammation.
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.
A Molecular Investigation Into Lipid-reactive Immunity To Combat Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$628,152.00
Summary
Tuberculosis (TB) infection currently causes ~1.5 million deaths annually. Due to new survival features acquired by the causative agent (Mycobacterium tuberculosis), traditional TB drugs and vaccines are becoming inefficient. Mycobacterium tuberculosis has a protective lipid-dense cell wall that is targeted by our immune system. We aim to understand the mechanisms of the lipid-mediated immune response to TB in order to develop more effective strategies to combat this disease.
Cytokine-driven Allergic Inflammation: Characterization Of Two Isoform-specific Modes Of IL-3 Receptor Activation And Investigation Of New Receptor-associated Signalling Partners.
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
In asthma, the symptoms are caused by an allergic reaction in the lung orchestrated by immune cells which produce small proteins called cytokines thus stimulating inflammatory cell production. The cytokine IL-3 is critical for the production of basophils which have an important role in the inflammation. The project will investigate the molecular details of how the IL-3 binds to its receptor and stimulates basophil production and reveal new targets for controlling inflammation in asthma.