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Antigen Presentation During HLA B27 Associated Auotimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$715,365.00
Summary
Ankylosing spondylitis is a debilitating arthritic disease, susceptibility to which is conferred by genes of the immune system, particularly HLA-B27, and following gastrointestinal infection. Using mass spectrometry we will identify bacterial peptides bound to HLA-B27 on infected cells that may trigger an autoimmune response. Defining the self peptides that remain the targets of autoimmunity will unravel the molecular and cellular mechanisms if disease and identify peptides for immunotherapy.
The Molecular Basis Of HLA-linked Drug Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$827,536.00
Summary
Adverse drug reactions are one of the leading causes of death in hospitalised patients. We discovered a new mechanism that links these reactions to recognition of drug induced changes in immunological self, resulting from interactions of drugs with immune receptors. This project continues to probe the mechanisms of immune mediated drug reactions by examining the basis of life threatening reactions to drugs used to treat epilepsy, gout and commonly used drugs such as penicillin and aspirin.
The Impact Of The Identification And Inclusion Of Acceptable HLA-mismatches On The Transplant Potential Of Highly-sensitised Renal Transplant Candidates.
Funder
National Health and Medical Research Council
Funding Amount
$100,323.00
Summary
In Australia, allocation of donor kidneys are currently weighted largely on the degree of donor-recipient HLA compatibility. However, not all HLA mismatches leads to negative outcomes. Acceptable HLA-mismatches are antigen mismatches that can be considered compatible at a structural and functional level and have been applied to circumvent the problem of difficulty finding suitable donors for highly-sensitised transplant candidates. We apply this concept to the Australian kidney transplant popula ....In Australia, allocation of donor kidneys are currently weighted largely on the degree of donor-recipient HLA compatibility. However, not all HLA mismatches leads to negative outcomes. Acceptable HLA-mismatches are antigen mismatches that can be considered compatible at a structural and functional level and have been applied to circumvent the problem of difficulty finding suitable donors for highly-sensitised transplant candidates. We apply this concept to the Australian kidney transplant population.Read moreRead less
The Molecular Basis Of HLA-linked Drug Hypersensivity Reactions
Funder
National Health and Medical Research Council
Funding Amount
$683,040.00
Summary
Adverse drug reactions are one of the leading causes of death in hospitalised patients. We have discovered a new mechanism that links these reactions to recognition of drug induced changes in immunological self, resulting from interactions of drugs with immune receptors. This project probes the generality of this mechanism by examining the basis of life threatening reactions to drugs used to treat epilepsy (carbamazepine), gout (allopurinol), HIV (Nevirapine) and towards aspirin a commonly used ....Adverse drug reactions are one of the leading causes of death in hospitalised patients. We have discovered a new mechanism that links these reactions to recognition of drug induced changes in immunological self, resulting from interactions of drugs with immune receptors. This project probes the generality of this mechanism by examining the basis of life threatening reactions to drugs used to treat epilepsy (carbamazepine), gout (allopurinol), HIV (Nevirapine) and towards aspirin a commonly used pharmaceutical.Read moreRead less
Antigen-specific Regulatory T Cells And HLA Associations In Autoimmune Renal Disease
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Glomerulonephritis (GN), a common cause of kidney failure, usually results from an immune system attack on the kidneys. Current treatments suppress the whole immune system, making patients vulnerable to infection. We aim to harness the body’s protective immune cells (Tregs) as a potential GN treatment. Using mice genetically programmed to mimic a human GN, we will test if specifically targeted Tregs protect mice from disease. We will also test how they affect blood samples from humans with GN.
Investigating The Aetiopathogenic Role Of Autoantibodies Against The M1 Muscarinic Acetylcholine Receptor In Patients With First Episode Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$830,986.00
Summary
Previously we have found that a proportion of patients with schizophrenia have elevated levels of antibodies that target one of the neurotransmitter receptors, the M1 muscarinic acetylcholine receptor, and that those patients who have the highest levels of antibodies tend to have more severe manifestations of some of the symptoms of schizophrenia. In this project, we will try to confirm this relationship, and also investigate further how this antibodies might be able to worsen specific symptoms.
Regulation Of Natural Killer Cell Activation By MHC Class I Molecules
Funder
National Health and Medical Research Council
Funding Amount
$697,084.00
Summary
Natural killer cells are important components of innate responses to viral infection and cancer. This project aims to better understand how these immune cells discriminate between healthy cells and those that have been infected with viruses or become cancerous.
Investigation Of Small Molecule Interactions With The Human Leukocyte Antigen And Their Role In Non-infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The Human Leukocyte Antigens (HLA) play a key role in the immune system helping the body differentiate healthy from diseased cells. Numerous autoimmune diseases and adverse drug reactions are associated with specific HLA variants. This study seeks to unlock the mechanisms behind these diseases, investigating how small molecules including drugs interact with the HLA to make healthy body cells seem foreign. This research has the potential to inform strategies for disease avoidance and management.
Analysis Of Human CD4+ T-cell Responses To Epitopes Formed By Peptide Fusion In The Pathogenesis Of Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,239,989.00
Summary
Type 1 diabetes is caused by immune-mediated destruction of the insulin-secreting beta cells. Recently we discovered new targets ‘seen’ by the immune system that may explain why the immune system causes type 1 diabetes. Here we will determine if responses to these targets cause type 1 diabetes. This is important because it tests a new idea and our results will have a major impact on efforts to develop new therapies for type 1 diabetes an other autoimmune diseases.
Tissue Specific T Cells Mediate Drug Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$1,253,980.00
Summary
T cells are immune cells that create dangerous and fatal drug allergies affecting the skin. An individual’s genetic makeup only partially explains predisposition to these reactions, we believe the missing link is contained in immune signatures specific to the skin. We aim to identify drug-specific T cells in the skin and develop a sensitive test to screen for rare, dangerous T cells in the blood. This will enable prediction and prevention of severe drug allergy and development of safer drugs.