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.
Understanding How Virus Infection Accelerates Type 1 Diabetes Development
Funder
National Health and Medical Research Council
Funding Amount
$610,774.00
Summary
We linked rotavirus infection in children at-risk of type 1 diabetes with faster diabetes development. A heightened response to the virus is implicated by our mouse model studies. We will determine if more rapid mouse diabetes due to rotavirus requires this heightened response, and if this response is also made by cells from diabetes patients after stimulation with rotavirus or other relevant viruses. These studies are vital to learn how viruses affect type 1 diabetes and devise interventions.
Apoptotic Pathways In Pancreatic Beta Cells Leading To Type 1 Diabetes And Transplant Rejection
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
The destruction of insulin-producing beta cells in the pancreas by immune cells leads to the need for daily insulin injections in patients with type 1 diabetes. This project aims to understand how beta cells are destroyed. A knowledge of the process by which this occurs will indicate ways we can protect these cells. Our previous work has suggested strategies that may protect beta cells, and we aim to test these. Such protection may eventually allow beta cell replacement by transplantation.
Targeting Drug-Resistance In Paediatric Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$649,048.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease, particularly for patients that develop drug-resistance such as those at the time of relapse.
A Preclinical Model Of Relapse In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$573,515.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease. We also hope to identify markers that can be used to screen for patients at increased risk of relapse.
Elucidating The Pathogenic Role Of Rotavirus Infection In Type 1 Diabetes Development
Funder
National Health and Medical Research Council
Funding Amount
$535,579.00
Summary
Rotavirus infection is the main cause of severe diarrhoea in children, and has been implicated in accelerated progression of genetically at-risk children towards type 1 diabetes in two independent studies. My group has further discovered that rotavirus also accelerates diabetes onset in mice in a novel immunological process. In this project, we will determine the mechanism behind this disease exacerbation in the mice, to facilitate understanding of the process in children.
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