Transcription Factors Which Regulate Signalling Through The Leptin-Melanocortin Pathway
Funder
National Health and Medical Research Council
Funding Amount
$586,704.00
Summary
Specific gene regulatory proteins define functions of various subsets of neurons in the hypothalamus. We will determine how interactions between three such proteins activate the leptin-melanocortin pathway, a hypothalamic signalling circuit that controls appetite. Defects in these proteins are found in obese patients who suffer from excessive eating disorders. The project will improve understanding of the genetic determinants of obesity and provide key points for development of new therapies.
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.
Role Of IS26 In Antibiotic Resistance Gene Recruitment, Dissemination And Expression
Funder
National Health and Medical Research Council
Funding Amount
$457,879.00
Summary
Antibiotic resistance is increasing, compromising the efficacy of front-line antibiotics. Untreatable infections due to bacteria that are resistant to all available antibiotics are being seen more often. To control the spread of resistance, an understanding of how resistance arises and is spread among bacteria is needed. This requires information about how the genetic elements that mobilize them work. This project will study one of the most important of these elements.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Post-GWAS Functional Characterisation Of Breast Cancer Susceptibility Loci
Funder
National Health and Medical Research Council
Funding Amount
$764,632.00
Summary
Recent studies have identified regions within the human genome in which DNA sequence variations are associated with an increased risk of breast cancer. Several of these regions do not contain any known genes, suggesting that regulatory DNA sequences are responsible for the associated risk. The aim of this proposal is to identify and characterise these DNA sequences. Understanding how sequences variations in these regions contribute to breast cancer will provide novel avenues for therapy.
Deciphering Specific Roles For The Common Arnt Proteins In BHLH/PAS Transcription Factor Complexes
Funder
National Health and Medical Research Council
Funding Amount
$526,421.00
Summary
Understanding the precise control of neuronal genes related to appetite and obesity, and neuropsychiatric disorders and dementia, is complicated by some gene regulating proteins having highly related sequences. This project will eludcidate how two closely related proteins can determine specific target gene outputs, information important for designing methods to control activities of neurological disease related genes within cells.
High-throughput Identification And Evaluation Of New Breast Cancer Genes From GWAS.
Funder
National Health and Medical Research Council
Funding Amount
$841,075.00
Summary
Recent studies have identified DNA markers within the human genome that are associated with an increased risk of breast cancer. Most of these markers are located in noncoding regions, therefore the key genes driving risk are not known. This proposal will identify the target genes at all breast cancer risk regions and assess how specific markers affect disease risk. Understanding how DNA variation contributes to breast cancer will provide new avenues for prevention or treatment.
Deciphering The Role Of DNA Methylation In The Regulation Of Alternative Splicing
Funder
National Health and Medical Research Council
Funding Amount
$865,494.00
Summary
When a gene is turned on, the messenger RNA must be correctly processed to generate functional proteins. This ‘splicing’ process is essential for normal cellular activity, and is disrupted in many human diseases. We have discovered that an epigenetic modification, DNA methylation (mC), may control splicing. This project will investigate how mC influences splicing and use new epigenome-editing tools to control it, in order to ultimately understand and treat diseases involving aberrant splicing.
Mechanisms Of Regulating Gene Expression Via Selective MRNA Transport
Funder
National Health and Medical Research Council
Funding Amount
$424,076.00
Summary
A critical step in the gene expression pathway that is altered in cancer is nuclear export of mRNA. We have demonstrated that mRNA export is not constitutive, but highly selective and can regulate distinct biological processes through poorly understood mechanisms. This project aims to dissect the molecular mechanisms of regulating gene expression via selective mRNA transport. This will establish selective mRNA export as a novel area of research in cancer biology.
Blood clotting is dependent upon platelets. A decline in platelet number, or thrombocytopenia, is a life threatening condition that can result from various diseases or importantly as a side effect of chemotherapy. We are investigating the control of platelet production. A long term goal is to stimulate platelet production in patients by boosting the natural pathways or to generate platelet producing cells for transfusion from a patient's own skin cells by genetic reprogramming.