Unraveling The Link Between HLA B27 And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$746,102.00
Summary
Ankylosing spondylitis and related diseases cause significant morbidity in up to 0.25% of the population. Current treatments have limited efficacy and often debilitating side effects. More targeted peptide antigen based therapies will have fewer side effects and would be of major clinical importance to this group of diseases. This project seeks to identify peptide antigens that could be used in targeted immunotherapy. We also seek to understand how some of the idiosyncratic properties of HLA B27
The Role Of MHC Class I Expression On Pancreatic Ductal Lineage Cells In The Pathogenesis Of Type I Diabetes (TID).
Funder
National Health and Medical Research Council
Funding Amount
$484,300.00
Summary
MHC molecules act as traffic lights to the immune system telling it whether to stop or go, so that only when there is an infection does the immune system receive the signal to destroy target cells. However, the immune system in Type 1 Diabetes patients receives signals to destroy the insulin-producing cells when there is no apparent infection. We aim to determine where the faulty traffic signal occurs and so be in a better position to design intervention strategies to prevent Type 1 Diabetes.
Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15), CCAAT/enhancer Binding Protein Delta (CEBPD) And Neuroinflammtion
Funder
National Health and Medical Research Council
Funding Amount
$459,270.00
Summary
I will develop new therapies for multiple sclerosis and spinal cord injury. I will also evaluate diagnostic and therapeutic uses for macrophage inhibitory cytokine-1 (MIC-1/GDF15) that was discovered in Australia. I will confirm its use in screening for bowel cancer. Also, I will look at using it in the indigenous and wider Australian community to improve health and close the gap in life expectancy. Finally, I will conduct trials of MIC-1/GDF15 therapy of obesity and inflammation.
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
Understanding Determinant Selection In Autoimmune Diseases
Funder
National Health and Medical Research Council
Funding Amount
$686,656.00
Summary
Understanding what the immune system perceives during infection or in autoimmunity is key to the development of improved vaccines and therapies for a variety of human diseases. This proposal builds on leading research into the definition of targets of immunity in autoimmune diseases using cutting edge proteomic technologies. The proposal focuses on type 1 diabetes, multiple sclerosis, lupus and rheumatoid arthritis and will delineate candidate therapeutic molecules.