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Excess inflammation is a major problem after injury and in many diseases. Upon injury molecules are release that act as danger signals to alert the immune system to start the repair process. However, high levels of these dangers signals can impair the final stages of healing. Understanding how to prevent the immune system being excessively stimulated by these danger signals is key to being able to dampen inflammation after injury improve the healing response.
Dengue Virus NS1 Protein As A Mediator Of Pathology
Funder
National Health and Medical Research Council
Funding Amount
$621,979.00
Summary
Dengue virus is an increasing problem in the tropical world, with estimated infection of more than 300 million people annually. Severe dengue disease can cause life-threatening bleeding and shock. Our project investigates the basis for the pathology of the disease. We have found that a viral protein termed NS1 binds to a receptor on immune cells and leads to production of inflammatory proteins which can promote vessel leakage. We will investigate drugs blocking this, in a disease model.
Innate Immune Signalling In Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$562,857.00
Summary
Tuberculosis (TB) is a major global health threat that causes 1.5 million deaths every year. This study will characterise a new molecular control mechanism that optimises the immune response to the bacteria that cause TB and determine how it contributes to controlling the infection. Such knowledge is essential to help improve patient management and develop better treatments for this devastating disease.
How Does Genetic Variation For Trig Affect Autoimmune Responses Mediated By Toll-like Receptors?
Funder
National Health and Medical Research Council
Funding Amount
$671,114.00
Summary
Juvenile diabetes is an autoimmune disease that affects more than 120,000 Australians. We have recently discovered a novel gene, named Trig, in a genetic study of mice that develop juvenile diabetes similar to children. This research proposal aims to determine the function of Trig in the immune system and how it contributes to the development of autoimmune diseases, such as juvenile diabetes.
Does CD123 Provide A Biological Advantage To Leukaemia Stem Cells?
Funder
National Health and Medical Research Council
Funding Amount
$647,637.00
Summary
Leukaemia is a devastating form of blood cancer affecting both young and old. We need to understand the diseased stem cell to eradicate this disease. Current therapy is poorly tolerated and the majority of patients ultimately die at relapse. We intend to investigate how we can make the cells more susceptible to therapy by understanding their biology.
Exploring And Targeting The Anti-Inflammatory Signalling Mechanisms Of Interleukin 37
Funder
National Health and Medical Research Council
Funding Amount
$1,018,306.00
Summary
Cytokines are messenger proteins that function as master regulators of biological processes; thus they play central roles in many diseases. The rare cytokines that block inflammation do so by dampening the immune system’s potentially destructive force, making them attractive targets for drug development. We showed that interleukin 37 is a powerful anti-inflammatory cytokine, and will now evaluate its mechanisms of action and its efficacy against several severe diseases, including cancer.
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.
Mechanism Of Activation Of JAK2 By A Class 1 Cytokine Receptor
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Cytokine receptors regulate key processes such as red/white blood cell formation, stature, adiposity and lactation. They use JAK kinases to signal to regulated genes. Here we will use sophisticated technologies able to observe single molecules and crystallography to uncover the mechanism used by these receptors to signal into the cell using a well characterised, simple cytokine receptor, the growth hormone receptor.
Structural And Functional Analysis Of Oncostatin M Receptor Signalling Complexes
Funder
National Health and Medical Research Council
Funding Amount
$519,284.00
Summary
Understanding how a chemical messenger selectively controls bone formation may lead to development of new therapies for osteoporosis and potentially other important diseases.