Thyroid hormones are regulators of development and metabolism. The lack of concordance of thyroid function and disease in identical twins suggests that environmental effects have a significant role. Quantifying epigenetic modifications, such as DNA methylation, has the potential to identify causal effects from the environment. This research will provide a comprehensive database of DNA methylome alterations that will contribute important insights into thyroid function in health and disease.
Organ-specific Autoimmunity: The Role Of The Thymus And Periphery In Shaping The Gastric-specific T Cell Repertoire
Funder
National Health and Medical Research Council
Funding Amount
$579,763.00
Summary
The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. White blood cells, called T lymphocytes are responsible for attacking our own tissues in autoimmune diseases. Our studies will employ a range of molecular, genetic and imaging technologies to track the rare and potential harmful white blood cells. Our studies should reveal the me ....The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. White blood cells, called T lymphocytes are responsible for attacking our own tissues in autoimmune diseases. Our studies will employ a range of molecular, genetic and imaging technologies to track the rare and potential harmful white blood cells. Our studies should reveal the mechanisms by which these self destructive T lymphocytes are silenced in healthy individuals on the one hand, and on the other hand escape to cause destruction in individuals with autoimmune diseases. This fundamental information will allow the development of therapeutic strategies to selectively turn-off these destructive T lymphoctyes in individuals with autoimmune disease and thereby remove the damaging immune response and cure the disease.Read moreRead less
Immunopathogenesis Of Organ-specific Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$284,638.00
Summary
The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. Our studies will employ state-of-the art technologies to further our knowledge of this class of diseases and to uncover the normal mechanisms that allow the immune system to differentiate foreign and self components.
Genetic And Biochemical Mechanisms Dysregulating CD4 T Cell Tolerance In Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$456,000.00
Summary
This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemical mechanisms that ....This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemical mechanisms that normally control T cell cell responses to self components, and how inherited defects lead these mechanisms to break down. The project focuses on defining how CD4 T cell regulation breaks down in two well established examples of inherited susceptibility to autoimmune disease. The direct action of autoimmune susceptibility genes will be determined at the level of the specific T cells responsible for autoimmune attack and in terms of the biochemical pathways within T cells that are dysregulated. By identifying the mechanisms and biochemical pathways that are dysregulated in autoimmune disorders, the results of this project will reveal targets for understanding and diagnosing autoimmune diseases and for developing new drugs or or vaccines to prevent T cells damaging vital organs and cure these diseases.Read moreRead less
Investigating T Cell Tolerance And Organ-specific Auotimmunity Using Autoantigen Deficient Mice
Funder
National Health and Medical Research Council
Funding Amount
$441,000.00
Summary
The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. Our studies will employ technologies to genetically manipulate mice to further our knowledge of this class of disease and to uncover the normal mechanisms that allow the immune system to prevent autoimmune attack. In particular we will gain information on the way that a new class ....The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. Our studies will employ technologies to genetically manipulate mice to further our knowledge of this class of disease and to uncover the normal mechanisms that allow the immune system to prevent autoimmune attack. In particular we will gain information on the way that a new class of lymphocytes, known as regulatory lymphocytes, are able to protect against autoimmune disease. Such regulatory lymphocytes have been identified in humans and are attractive therapeutic agents to prevent a variety of immune-mediated diseases, including autoimmune diseases, allergy and transplantation rejection.Read moreRead less
Genetic And Molecular Mechanisms Dysregulating CD4 T Cell Tolerance In Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$575,947.00
Summary
This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, Addison s disease and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemic ....This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, Addison s disease and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemical mechanisms that normally control T cell responses to self components, and how inherited defects lead these mechanisms to break down. The project focuses on defining how CD4 T cell regulation breaks down in a well established but poorly understood example of polygenic inherited susceptibility to autoimmune disease. Polygenic diseases are those where susceptibility is inherited in a complex way involving many different genes either acting together or in opposition, and the molecular basis for this kind of inheritance is particularly poorly understood. The project will analyse the basis for this kind of inheritance pattern by analysing the direct action of diabetes susceptibility genes at the level of the specific T cells responsible for autoimmune attack and in terms of the biochemical pathways within the T cells that are dysregulated. By identifying the mechanisms and biochemical pathways that are dysregulated in autoimmune disorders, the results of this project will concepts and targets for understanding and diagnosing autoimmune diseases and for developing new drugs or vaccines to prevent T cells damaging vital organs and cure these diseases.Read moreRead less