Growth hormone is responsible for normal postnatal growth, is an important metabolic regulator in starvation, and has many useful therapeutic applications, including forms of cardiac insufficiency, Crohns disease and, it is thought, amelioration of ageing. The means whereby GH brings about these changes are not known, although we do know a considerable amount about how the individual domains within the GH receptor signal. What we do not know is which genes are regulated by GH in these processes, ....Growth hormone is responsible for normal postnatal growth, is an important metabolic regulator in starvation, and has many useful therapeutic applications, including forms of cardiac insufficiency, Crohns disease and, it is thought, amelioration of ageing. The means whereby GH brings about these changes are not known, although we do know a considerable amount about how the individual domains within the GH receptor signal. What we do not know is which genes are regulated by GH in these processes, and how this will change the state of the cell. We propose here to use the new technique of gene arrays to uncover the programs, or groups of genes, which GH regulates to change important cellular processes. When used in conjunction with cells expressing GH receptor mutants which are unable to signal to defined pathways, we will be able to know which functional families genes are regulated, and how they are regulated. This information will enable us to know how GH regulates cell growth and metabolism, and therfore to understand what goes wrong when GH or its mediator, IGF-1 , are abnormal. We can also use this information to validate small molecules designed to mimic GH through activating its receptor, to be certain that they are acting in the same way as GH.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
Understanding The Complexity Of Antigen Presentation
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
I have developed and established the use of mass spectrometry to identify and quantitate ligands of antigen presenting molecules to understand the breadth of immune responses in a variety of human disease states including autoimmunity, cancer, infection and allergy. By embedding the technology in disease focussed research programs I will define the molecular bases of these diseases and the important immunological targets that will provide new avenues for therapeutic development and vaccines.
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.