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.
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.
Intravascular Leukocyte Trafficking During Thromboinflammation
Funder
National Health and Medical Research Council
Funding Amount
$668,742.00
Summary
Unblocking blood vessels to treat heart attack and stroke can unfortunately cause a paradoxical worsening of organ damage, due to increased inflammation upon blood flow restoration. We have identified a novel way in which this side-effect is regulated by the small blood clotting cells platelets, and the protein fibrin. We will investigate ways to reduce the pro-inflammatory role for platelets, and define safer clot busting treatments.
Deciphering Mechanisms Of Liver Allograft Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$520,964.00
Summary
The liver has paradoxical properties: it is the site of effective immune responses to pathogens, but under some circumstances, it is known to induce harmless immune responses. Liver transplants are more readily accepted than other organ grafts in the absence of immunosuppressive drugs but little is known about the mechanisms that prevent an effective response. This proposal aims to unravel these mechanisms. This project will have important implications for transplantation studies.
De Novo Mutations And The Pathogenesis Of Childhood-onset Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,406,510.00
Summary
This project aims to reveal the gene abnormalities that cause devastating autoimmune diseases to develop in some children, such as Type 1 diabetes, juvenile arthritis and autoimmune destruction of blood cells. The project will use new technologies to identify alterations in the DNA sequence of a child compared to either of their parents, and to test suspicious DNA alterations in laboratory mice in order to understand the gene effects and evaluate new treatments.
Contribution Of Disturbed Blood Flow And Cerebral Metabolism To White Matter Damage In The Perinatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$369,375.00
Summary
It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral ....It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral palsy. Such outcomes are often associated with the presence of asphyxia and infection during pregnancy, leading to the belief that the damage first arises while the baby is still in utero. In this application we suggest that asphyxia and-or infection during pregnancy cause prolonged disturbances in the regulation of blood flow and integrity of the blood-brain barrier in the developing brain, together with changes in metabolism that result in accumulation of prostaglandins and the toxic hydroxyl radical, leading irreversibly to cell death. If this series of events proves to be true, we have suggested and will test several protocols for protecting the fetal brain, which should be readily translatable to clinical practice.Read moreRead less