Regulation Of Autoimmunity By Non-apoptotic Caspases
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Excessive cell death can lead to chronic inflammation and autoimmunity. Cells can die by different mechanisms including necroptosis which causes inflammation, and apoptosis which does not. Recent studies show that caspases, a component of the apoptosis pathway which accelerate cell death, also prevent immune activation by dying cells. I will investigate whether caspases contribute to autoimmune disease and whether caspases can dampen the inflammation that occurs during necroptotic cell death.
Molecular And Cellular Studies Of The Adaptive Immune Response In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$16,509,154.00
Summary
Immune responses protect us against pathogens such as viruses and bacteria. However inappropriate immune responses can result in autoimmune conditions such as systemic lupus erythmatosus, multiple sclerosis, type I diabetes, asthma as well as immunodeficiencies. The aim of our proposal is to gain a thorough understanding of how all the cells of the immune system function and interact with each other, and what goes wrong when inflammatory diseases develop. We plan to do this using state-of-of-the ....Immune responses protect us against pathogens such as viruses and bacteria. However inappropriate immune responses can result in autoimmune conditions such as systemic lupus erythmatosus, multiple sclerosis, type I diabetes, asthma as well as immunodeficiencies. The aim of our proposal is to gain a thorough understanding of how all the cells of the immune system function and interact with each other, and what goes wrong when inflammatory diseases develop. We plan to do this using state-of-of-the-art technologies, including genetically modified mice, gene microarrays, monoclonal antibodies, and flow cytometry. We have brought together Australia's leading immunologists with complimentary expertise and research interests in specific areas of immunology including cytokines, cell migration, inflammatory diseases, autoimmunity and cell-cell interactions. One aspect of the application is to understand the genetic and molecular basis of immunological diseases. However we also wish to move on from an understanding to treatment of immunological diseases through the development of novel therapeutics. We will form collaborations with biotech and pharmaceutical companies (including our own spin off companies) to advance important new therapeutics for autoimmune and allergic diseases. These conditions represent a significant health burden to Australia.Read moreRead less
My research is directed to the prevention of diabetes, across the spectrum from type 1 to type 2 diabetes. It is based on understanding immune-inflammatory mechanisms that contribute to dysfunction and death of pancreatic insulin-secreting beta cells and tissue resistance to the action of insulin. I study these mechanisms in rodent models and in humans in the context of relevant environmental factors and genes, with the aim of manipulating them for therapeutic benefit.
In Vivo Investigation Of Human PR3 Transgenic Mice: A Novel Animal Model To Understand The Role Of PR3 In Chronic Inflammation And Autoimmune Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$378,615.00
Summary
Granulomatosis with polyangiitis (GPA) is a form of vasculitis and is associated with antibodies directed against proteinase 3 (PR3). PR3 is expressed in neutrophils, monocytes and macrophages and has a number of well-characterized pro-inflammatory functions. The aim of this project is to understand the role of PR3 in inflammation and autoimmune vasculitis in vivo. This will be achieved using a transgenic mouse model expressing human PR3.
Development Of Endogenous Granulocyte Colony Stimulating Factor (G-CSF) Antagonism As A New Therapeutic Approach To Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$401,561.00
Summary
Neutrophils play a pivotal role in inflammatory diseases including rheumatoid arthritis (RA). G-CSF is a growth factor that is important to neutrophil survival and function. We have shown that in the absence of G-CSF the incidence and severity of experimental autoimmune arthritis are reduced. We will investigate the mechanisms by which this occurs as well as studying the effects of G-CSF blockade on function and survival of human neutrophils from healthy donors and RA patients.
Development Of A Safer New Treatment For Systemic Lupus Erythematosus That Preserves B Cell Immunity
Funder
National Health and Medical Research Council
Funding Amount
$672,008.00
Summary
Lupus is an illness characterized by the body’s immune system attacking the body itself. More than 5 millions of people worldwide suffer from lupus, in particular Indigenous Australians who are 4 times more likely to develop lupus. Current treatments are toxic and/or lack efficacy. In this proposal we use strong new evidence from the laboratory to support the design of a much safer and more effective treatment for lupus that will be validated for future use in patients.
Exploring The Contribution Of Interferon-lambda To Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$833,235.00
Summary
We have found that a novel protein, normally made in response to viral infections, is found in the blood of Lupus patients. This project will determine the cells that make this protein, what in Lupus blood makes these cells produce it and whether it plays a role in the severity of Lupus disease.
Defining The Cellular And Molecular Mechanisms Underlying Autoimmunity Using A Model Of SLE
Funder
National Health and Medical Research Council
Funding Amount
$624,960.00
Summary
The immune system has to recognize the difference between foreign pathogens, which it should attack, and ourselves, which it should not. Autoimmune diseases, like lupus, occur when our immune systems attack our own tissues due to problems in regulation. We have developed an animal model of lupus that has allowed us to identify major points where immune regulation has failed. Identifying these checkpoints will allow us to design and trial novel therapeutics in lupus.