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The Impact Of Obesity On Immunological Tolerance Of The Fetus
Funder
National Health and Medical Research Council
Funding Amount
$378,366.00
Summary
Obesity increases the risk of miscarriage during pregnancy. The reasons for this are not known, although it is thought that abnormal levels of hormones and metabolic parameters are a contributing factor. We hypothesise that the immune system plays a role. In this project we will determine if obesity upsets the fine-tuning of the immune system that is crucial for successful pregnancy. Understanding the reason behind adverse pregnancy outcome will allow appropriate management of maternal obesity.
MAIT cells are a recently discovered type of lymphocyte that plays a unique and important role in the immune system. However, these cells vary widely in number between healthy individuals, for reasons that are unclear. This project is designed to understand the factors that control the development of MAIT cells as a step toward regulating their numbers and activity.
Regulatory T Cells And Cardiac Fibrosis In Hypertensive Heart Disease: Cellular And Molecular Mechanisms Of Suppression
Funder
National Health and Medical Research Council
Funding Amount
$715,316.00
Summary
Excessive accumulation of collagen in the heart, cardiac fibrosis is a major factor causing heart failure and sudden death. How collagen accumulation occurs in the heart still needs to be elucidated but recent studies in humans and animal models of cardiac fibrosis indicate a significant role for inflammation. The proposed studies are to address this issue and how to regulate inflammation in the heart to suppress cardiac fibrosis, using immune cells called regulatory T cells that suppress inflam ....Excessive accumulation of collagen in the heart, cardiac fibrosis is a major factor causing heart failure and sudden death. How collagen accumulation occurs in the heart still needs to be elucidated but recent studies in humans and animal models of cardiac fibrosis indicate a significant role for inflammation. The proposed studies are to address this issue and how to regulate inflammation in the heart to suppress cardiac fibrosis, using immune cells called regulatory T cells that suppress inflammation.Read moreRead less
Elucidating The Mechanism Of IL-2 Cytokine/antibody Mediated Transplantation Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Organ transplantation is a life-saving treatment for end-stage organ failure. However, patients must take immunosuppressive drugs to prevent rejection, a lifetime of which increases the risk of infection and cancer. An alternative to drugs is to manipulate the immune system from within. We discovered a way to boost the immune ‘regulators’ so that they stifle the graft-destroying response. We are optimising this approach with the aim of transplanting organs without long-term immunosuppression.
The Role Of NF-?B Transcription Factor RelA In Regulatory T Cell Homeostasis And Function
Funder
National Health and Medical Research Council
Funding Amount
$637,114.00
Summary
Treg cells constitute an immune regulatory cell population that is essential for the prevention of fatal autoimmunity; however, they also limit immunity against cancer. We have discovered that the factor RelA is of critical importance for Treg development and function. We now aim to illuminate the functions of RelA in detail. Understanding the molecules that impact on Treg cell biology is critical to harness their potential for clinical intervention such as treatment of autoimmunity and cancer.
The Role Of Regulatory T Cells In Rapidly Progressive Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$581,113.00
Summary
Inflammation of the kidneys is an important, yet poorly understood cause of kidney disease in Australia. As part of our endogenous defenses against inflammation, we have cells called regulatory T cells that dampen inflammation and are protective. This project will define the role of some of these cells and examine potential ways to use them do dampen kidney inflammation.
Molecular And Functional Charcterization Of A Novel Population Of Foxp3+ Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$394,274.00
Summary
Regulatory T cells (Tregs) are essential for the prevention of autoimmunity and death. We have identified a new population of effector or ïactiveÍ Tregs, and identified some of the proteins that are required for these cells to function. We now aim to examine the development of these cells in detail, illuminate their precise function, their distribution and mode of action. This has potentially huge implications in treatment and diagnosis of autoimmunity, cancer or transplantation.
Targeting Caspase 8 In T-Cell Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,215,780.00
Summary
Chronic infectious diseases such as HIV, hepatitis B and tuberculosis impose a massive global health burden and new treatments are desperately needed. This proposal investigates a new approach to improve immune responses and clear chronic infections. Our multidisciplinary team will define the molecular and cellular biology underlying this approach and translate our findings by re-purposing a drug already approved for other indications in humans.
The Role Of The Transcription Factor Blimp-1 In Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$642,674.00
Summary
Regulatory T (Treg) cells function by suppressing immune system activity, ensuring that our immune system does not mount a response against our own tissue. In cancer, Treg cells suppress anti-tumour immunity, facilitating tumour growth. Recently we have identified a group of active Treg cells that may be the key drivers of immune response regulation. Our work will examine the role of these active Treg cells in tumour immunity, opening the door to more effective targeting of Treg cells in cancer.
Maintenance Of Regulatory T Cells During Inflammation And Tumor Development By IL-33
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Regulatory T cells (Tregs) are required for preventing inflammation in tissues such as lung, fat and skin. We found recently, that the signalling molecule IL-33 is required for tissue Tregs and up-regulated during inflammation and tumor development. We therefore aim to determine the role of IL-33 in maintenance and function of Tregs and to identify molecular targets of IL-33 that may allow therapeutic targeting of Tregs in patients with inflammatory conditions or cancer.