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.
Analysis Of The Role Of Rotavirus Infection In Development Of Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$348,875.00
Summary
Our earlier studies in children with a family history of type 1 diabetes have shown that infection with a common virus, rotavirus, may be one factor contributing to their progression to diabetes. Rotavirus is the most common cause of diarrhoea, vomiting and dehydration in young children, and it was thought that rotavirus infection is usually confined to the intestine. To understand how rotavirus infection might promote diabetes, my group has developed a mouse model. Using mice for these studies ....Our earlier studies in children with a family history of type 1 diabetes have shown that infection with a common virus, rotavirus, may be one factor contributing to their progression to diabetes. Rotavirus is the most common cause of diarrhoea, vomiting and dehydration in young children, and it was thought that rotavirus infection is usually confined to the intestine. To understand how rotavirus infection might promote diabetes, my group has developed a mouse model. Using mice for these studies allows us to control infection and completely analyse the results of infection, which we cannot do in humans. A type of mouse that is very likely to develop type 1 diabetes in its first 6 months of life is infected by mouth with rotavirus. We have shown that these mice develop diabetes 7 weeks faster than the same type of mice that are not given virus. In this project, we will determine the effects of mouse age, virus strain, the number of times infection occurs, and levels of virus growth in the intestine or pancreas on virus-induced diabetes acceleration. The ability of treatments for rotavirus infection, and vaccination against rotavirus, to block this accelerated diabetes also will be tested. We expect that rotavirus will be found growing in the pancreas, that virus growth is necessary for diabetes acceleration, and that prevention of rotavirus infection will also prevent the rapid diabetes onset. This model could prove to be suitable for testing the effectiveness and safety of new drugs and vaccines against both rotavirus and type 1 diabetes. Our studies will be crucial in determining the importance of rotavirus infection in the development of type 1 diabetes.Read moreRead less
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.
Mechanism Of Protection Of Islet Beta Cells From T1D By Heparan Sulfate
Funder
National Health and Medical Research Council
Funding Amount
$602,453.00
Summary
Type 1 diabetes (T1D) is an autoimmune disease which destroys the insulin-producing beta cells in the pancreas. Current insulin therapy does not prevent the development of serious secondary complications. We have discovered that beta cells require a complex sugar (heparan sulfate; HS) for their survival and that T1D is prevented when an enzyme, heparanase, that degrades HS is inhibited. Understanding these mechanisms will identify new therapeutic strategies for preventing T1D progression.