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A Novel Role For The IL-2 Pathway In Type-1-diabetes.
Funder
National Health and Medical Research Council
Funding Amount
$548,548.00
Summary
Genes encoding IL-2 and its receptor are strongly linked to susceptibility to multiple autoimmune diseases, including type-1-diabetes. Despite the importance of this pathway in the immune system, it is not yet understood how the associated genes affect disease. In this study, a novel function for IL-2 expression by dendritic cells in normal self-tolerance is investigated. The impacts of dendritic cell produced IL-2 expression and linkage to autoimmunity will be elucidated in both mouse and man.
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.
At least 6 young Australians are diagnosed each day with type 1 diabetes. This Program aims to change the way type 1 diabetes is managed by proactively treating its underlying mechanisms. We will develop safer and more effective immune therapies, develop islet transplantation, look for better markers of disease, and identify ways to preserve insulin-producing cells. The Program aims to propel type 1 diabetes research forward to reach the goals of prevention and cure.
The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to tes ....The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to test and identify people at risk for type 1 diabetes. They showed that the underlying disease could start years before symptoms occurred and discovered genes that determine the rate at which the underlying disease progresses. They have also found evidence that the disease may be triggered by gut viruses called rotaviruses in genetically-susceptible individuals. They showed that type 1 diabetes could be prevented in a mouse model by getting the immune system to make a protective response to insulin, and then went on to apply this in at-risk humans in a controlled trial of intranasal insulin, the first of its kind. They have used genetic techniques not only to pinpoint the mechanisms responsible for killing the beta cells but also to modify the beta cells to make them resistant to attack by these mechanisms. The multidisciplinary approach of the team will be directed to further understanding the genetic and environmental factors underlying type 1 diabetes and the immune mechanisms, particularly involving special white blood cells called T cells, that kill beta cells. A molecular target of the immune attack, the parent of insulin called proinsulin, will be used, paradoxically, as a tool to regulate the immune system and avert the attack. This will be achieved by giving proinsulin via the mucosa of the naso-respiratory tract or via the bone marrow-derived stem cells, initiallyin the mouse model as a test of feasibility for human application. In parallel with these approaches to prevention, specially constructed viruses will be used to transfer several new genes into beta cells to improve their resistance to immune attack, so that they can be transplanted into people with established diabetes without the need for potentially toxic drugs that suppress the immune system overall. The integrated research of the team is helping to provide a sound, rational base for the eventual prevention and cure of type 1 diabetes.Read moreRead less
Cellular Pathogenesis Of Key Proteins Involved In Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$312,730.00
Summary
Prion proteins are involved in neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and Bovine Spongiform Encephalopathy (BSE). The aim of this research proposal is to investigate factors which can change the prion protein from a normal, benign, form into an abnormal shape which can cause disease. The outcomes of this work will provide further insight into the role of prion proteins in these diseases and also for other neurodegenerative disorders such as Alzheimer's disease.
Investigations In Multiple Sclerosis Patients With Coexistent Autoimmune Thyroid Disease
Funder
National Health and Medical Research Council
Funding Amount
$557,100.00
Summary
Multiple sclerosis (MS) is a common chronic neurological disease affecting over one million people around the world. MS is generally thought to be an autoimmune disease, in which a person's own immune cells start to attack components of the brain and spinal cord. However, it is thought that the same components are not attacked in all patients, and that the pathway that leads to MS varies from one person to another. Therefore, in order to develop successful treatment strategies for MS, it will be ....Multiple sclerosis (MS) is a common chronic neurological disease affecting over one million people around the world. MS is generally thought to be an autoimmune disease, in which a person's own immune cells start to attack components of the brain and spinal cord. However, it is thought that the same components are not attacked in all patients, and that the pathway that leads to MS varies from one person to another. Therefore, in order to develop successful treatment strategies for MS, it will be necessary to look for patterns in the clinical symptoms and signs and other features of a person's MS that may give clues as to which particular pathway is leading to disease in that person. Some people who develop MS also develop other autoimmune diseases, or have these other diseases before they develop MS, or have other family members who have other autoimmune diseases. We have recently found that people who have the same combination of coexistent MS and autoimmune thyroid disease (AITD) show similar clinical signs of MS, and tend to have damage (lesions) to the same areas of their nervous system. This suggests that these people may have the same underlying pathways leading to the development of MS, and that they may be a very informative group in which to look for immune or genetic abnormalities that might explain why they develop MS. This project will investigate people who have both MS and AITD and other members of their families to see if we can work out what the links are between having the same combination of autoimmune diseases and developing lesions in particular parts of the nervous system. It will provide information on the pathways that lead to the development of MS, and information obtained from this study may eventually be of use in developing more specific therapeutic agents, by tailoring therapies to specific people with MS, depending on the clinical and immunological profile of that person.Read moreRead less
The Influence Of NF-KB In The Development Of Autoimmunity And Cancer In Fas/FasL Mutant Mice
Funder
National Health and Medical Research Council
Funding Amount
$596,925.00
Summary
Apoptotic cell death is an essential process in the human body, it removes useless and dangerous cells, preventing autoimmune disease and cancer. Apoptosis is activated when the surface receptor Fas is stimulated by its ligand, FasL, but defective signalling causes disease associated with deregulated NF-?B activation. We will investigate how faulty FasL-induced apoptosis cooperates with deregulated NF-kB activation or defective Aire (immunological tolerance orchestrator) results in autoimmunity.
The Role Of Susceptibility Genes And Microbiota In Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$303,924.00
Summary
Utilising my background in Immunology I will investigate whether specific genetic mutations can create a susceptibility for dysregulation of the flora and immune system within the gut, thus predisposing an individual to inflammatory bowel diseases (ulcerative colitis and Crohn's disease) as well as non-intestinal inflammatory conditions. These diseases are becoming an increasingly prevalent and serious health burden in Australia. We aim to use this knowledge in order to design specific treatment ....Utilising my background in Immunology I will investigate whether specific genetic mutations can create a susceptibility for dysregulation of the flora and immune system within the gut, thus predisposing an individual to inflammatory bowel diseases (ulcerative colitis and Crohn's disease) as well as non-intestinal inflammatory conditions. These diseases are becoming an increasingly prevalent and serious health burden in Australia. We aim to use this knowledge in order to design specific treatments for these diseases.Read moreRead less