Unraveling Mechanisms Of Liver Transplant Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$694,822.00
Summary
Liver transplants are unique amongst solid organs as they are spontaneously accepted across different individuals and induce acceptance of other organs from the same donor co-transplanted at the same time. Using a new mouse liver transplantation model, this proposal will elucidate how the liver tissue performs this function and identify new markers associated with tolerance in the blood of mice. This knowledge will be used to identify liver transplant patients with reduced rejection risk.
Impaired Respiratory Tolerance In Obesity - The Link With Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$667,294.00
Summary
Australia has one of the highest obesity rates in the world, placing a major strain on health budgets. Obesity increases the risk of numerous diseases, including asthma. Asthma is prevented in healthy people by the immune system. This project will investigate whether obesity-related dietary factors and/or gut microbes impair this immune-mediated mechanism. Outcomes will increase understanding of the effects of diet and obesity on asthma development, and lead to novel asthma therapies.
Deciphering How TCR Affinity Regulates CD4 T Cell Help In Immunity And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$850,885.00
Summary
Immune responses require the coordinated interaction and cross-talk between two types of white blood cells known as CD4 and CD8 T cells. A dysregulated interaction between these cells could be the cause of autoimmune and persistent infections by pathogens leading to chronic diseases. The aim of this proposal is to provide a deeper understanding of CD4/CD8 T cell interactions to improve immune outcomes in many chronic diseases in which interaction between these two immune cells is critical.
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.
Prevention Of Autoimmune Diabetes By Immune Tolerance To Proinsulin
Funder
National Health and Medical Research Council
Funding Amount
$504,597.00
Summary
In type 1 diabetes, insulin is the first target of the immune system. Strategies to prevent the immune system targeting insulin in mice early in the disease process work, but it is not clear if such strategies would be effective if applied late. This is important because preventive therapies for human type 1 diabetes are currently feasible only late in the disease process. We aim to address this by removing T cells specific for insulin at different stages of the disease.
The Male Partner Contribution To Pregnancy Immune Tolerance Deficit In Women
Funder
National Health and Medical Research Council
Funding Amount
$1,462,925.00
Summary
A complication-free pregnancy and birth of a healthy infant depends on adequate preparation of the mother's immune system to tolerate the 'foreign' fetus, Both the mother and the father contribute to establishing optimal immune tolerance. This project will determine the links between specific agents in male seminal fluid and the female immune response, and will make progress towards new diagnostic tests and treatment options for unexplained subfertility and gestational disorders.
How Deletional And Non-Deletional Tolerance Mechanisms Integrate To Prevent Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$509,944.00
Summary
The body produces millions of immune cells every day to fight infection. Some of these immune cells are defective and dangerous because they can cause autoimmune diseases, like Type I diabetes and multiple sclerosis. To defuse this risk, such immune cells are either caused to die or are inactivated to prevent autoimmunity. We propose to investigate how the processes of immune cell death and inactivation work in health and disease so we may harness these mechanisms to cure autoimmunity.
Modified Peanut Allergen Combined With A Novel Dietary Adjuvant As A Cure For Peanut Allergy: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,130,021.00
Summary
Peanut allergy is common and there is no cure. Current studies of peanut immunotherapy have shown the effects are not generally long lasting with many side effects. We plan to study a novel form of oral peanut immunotherapy using modified peanut and a dietary fibre (modified starch) supplement. We have evidence that modified peanut may work to desensitise patients with less side effects and that the diet supplement protects animals from developing food allergy.
Bridging The Gap In Kidney Transplantation Using Pigs As Donors
Funder
National Health and Medical Research Council
Funding Amount
$1,452,341.00
Summary
Chronic kidney failure results in patients suffering significant morbidity and mortality ultimately requiring life-supporting dialysis. Kidney transplantation and lifelong immunosuppression are the only treatment, but (i) is limited by the shortage of human donors and (ii) carries risks associated with these anti-rejection drugs. This project aims to solve both problems by using humanized pigs as donors combined with a novel approach to inducing acceptance of the transplanted kidneys.
Therapeutic Potential Of Peritoneal Mononuclear Phagocytes From Peritoneal Dialysis Patients
Funder
National Health and Medical Research Council
Funding Amount
$375,817.00
Summary
Mononuclear phagocytes (MP) are key cells which are now being used to treat various diseases. In Australia, more than 10 million end stage kidney disease(ESKD) patients are treated with chronic dialysis, and more than 20% of them are on peritoneal dialysis (PD). Each PD patient discards more than 20 million MP in dialysate daily. We will explore the possibility of using these MP to treat diseases including transplant rejection.