Alternate Splicing Of Tryptase Genes Regulates Their Specificity
Funder
National Health and Medical Research Council
Funding Amount
$294,250.00
Summary
Tryptases are enzymes implicated in inflammatory disorders including arthritis, inflammatory bowel disease (IBD) and asthma. Specific tryptase inhibitors are effective in treating these diseases. We have discovered that each human tryptase gene is processed into two different protein products via a mechanism called alternate splicing. We will investigate the structure and function of these.
Genomic Characterisation Of Novel Inflammatory Regulators In A Mouse Model Of Disseminated Candidiasis
Funder
National Health and Medical Research Council
Funding Amount
$581,427.00
Summary
Genome biology offers great promise for the study of immune function, but new approaches are needed to build insights between data and disease. This project looks at the gene products used by mice susceptible to yeast infection and asks if the information is used differently in resistant animals. Blood-borne fungal infections are increasing in hospitals; we want to discover new immune gene products and understand how they contribute, so we can better predict the outcome of an infection.
Cancer arises through a combination of common DNA mutations which are associated with very poor survival in certain cancers. However, the cause of these mutations was always believed to be external factors (eg. UV light, toxins), Our exciting preliminary results show internal molecules, called circular RNAs, can drive these mutations and this project will investigate how this occurs and study whether targeting these molecules can reduce the incidence of cancers.
Circular RNAs As Genome Destabilisers In Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$2,163,220.00
Summary
Mutation of genes are hallmarks of both cancer and neurological disorders. My research group has identified roles for circular RNAs in both these processes. Now, we must close the loop by investigating the mechanism of these processes. This will inform not only why these genes are commonly mutated, but by exploiting the highly stable circular RNAs they may provide early prognostic/diagnostic biomarkers and even represent novel therapeutic targets for cancer and Huntington’s disease.
Uncovering New Epigenetic-based Regulatory Mechanisms Of Gene Expression: Novel Links Between Histone Variants, RNA Function And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,053,671.00
Summary
It is estimated that greater than 90% of human genes undergo alternative RNA splicing, which can explain how protein diversity is achieved with a limited number of genes. However, how alternative splicing patterns are established remains poorly understood but is an important question given that 15-50% of human disease mutations are associated with changes to the splicing patterns of RNA. We have uncovered a new splicing mechanism, which involves changing the way DNA is packaged in a cell.