A New Paradigm For Class I Cytokine Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$954,946.00
Summary
Class I cytokine receptors include around 30 receptors with diverse functions such as controlling metabolism and inflammation. Cytokine receptors are molecular switches on cells that receive signals from other cells and transmit this signal into the cell’s nucleus to control the regulation of genes. This project will determine the molecular mechanisms involved in class I cytokine receptors and use this knowledge to develop novel ways to modulate these receptors for clinical applications.
Interactions Between RAGE And The Type 1 Angiotensin Receptor Determine The Pro-atherosclerotic Actions Of Angiotensin II
Funder
National Health and Medical Research Council
Funding Amount
$521,956.00
Summary
Heart attacks and strokes are a major cause of death and disability in Australians. Activation of the renin angiotensin system plays a key role in the development and progression of atherosclerosis, the process that leads to narrowing and obstruction of arteries. In preliminary data we have found a way to block these pathways without affecting the control of blood pressure. We believe that interventions based on these data will be important for the prevention and treatment of heart disease.
Understanding The Role Of The Putative Phospholipid Translocase ATP11c In B Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$455,153.00
Summary
The immune system protects humans against recurrent infections with a wide range of pathogens. Formation of antibodies is a crucial element of the immune response. Defects in the production of antibodies can lead to recurrent and often life-threatening infections. This project seeks to understand a genetic defect in mice resulting in an almost complete absence of antibody producing cells, thereby causing a disease that is similar to some forms of human immunodeficiency.
Spatial And Temporal Dimensions Of Mu-opioid Receptor Signalling: Implications For The Development Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$799,316.00
Summary
The use of morphine as an analgesic is still limited by undesirable side effects such as tolerance. Despite decades of research, the mechanisms behind the development of tolerance are poorly understood. The ? opioid receptor is a protein expressed at the surface of the cells that is the target of morphine. This project will investigate the signalling events triggered by opioids with unprecedented resolution and will aim to elucidate why morphine elicits more tolerance than other opioid drugs.
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.
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.
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.
Macrophage Polarisation And Control Of Pulmonary Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$895,494.00
Summary
As key immune cells, macrophages are polarised to phenotypes that turn inflammation on or off. In cystic fibrosis, defective macrophage polarisation enhances inflammation and prevents lung repair. We are defining the molecules and cellular pathways that control this process and identifying targets for existing drugs that can be used to reprogram macrophages and restore lung repair to improve patient outcomes.
Developing A New Strategy For Treating Demyelinating Peripheral Diseases
Funder
National Health and Medical Research Council
Funding Amount
$496,250.00
Summary
Incomplete remyelination is a significant component of the persistent clinical disability of peripheral demyelinating neuropathy, contributing to conduction deficits and the secondary axonal damage. A crucial therapeutic challenge is to identify ways to promote remyelination. This project aims to develop a new strategy and a novel clinically relevant target for treating peripheral demyelinating neuropathy.
How Does NF-kB2 Regulate Thymic Selection To Prevent Organ-specific Autoimmune Disease?
Funder
National Health and Medical Research Council
Funding Amount
$787,600.00
Summary
Autoimmune diseases like type 1 diabetes and thyroiditis arise from defects that cause the immune system to confuse self and non-self. Normally, this distinction is programmed in the thymus. We recently identified the gene that causes a form of autoimmune disease. We also made an important discovery about how the thymus gland regulates self-non-self discrimination. We will build on these two discoveries to gain a precise understanding of how the immune system normally avoids autoimmune disease.