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Identifying Regulators Of The DNA Damage Response And Tumourigenesis Using C. Elegans
Funder
National Health and Medical Research Council
Funding Amount
$514,367.00
Summary
By the age of 85, one in two men and one in three women in Australia will develop cancer. Regrettably, not all cancers respond to current therapies. Recently a new mechanism that prevents certain cancers from responding to chemotherapy has been identified, involving a protein called HIPK. We are using a simple model system, the nematode Caenorhabditis elegans, to discover ways in which this block to successful cancer treatment can be overcome, with the view to developing new therapeutic agents.
TAF8 is a small protein that is associated with the general transcriptional apparatus. TAF8 is not an essential part of the general transcriptional machinery, but rather a regulatory molecule that appears to dictate how the machinery is used to express different genes. The absence of TAF8 leads to expression of genes controlling cell death. Since the avoidence of cell death is essential to the development of cancer these results will lead to a better understanding of how cancer develops.
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.
The Role Of Novel And Essential Bromodomain Proteins In Coordinating Malaria Parasite Gene Regulation And Their Potential As Anti-malarial Targets
Funder
National Health and Medical Research Council
Funding Amount
$689,034.00
Summary
Malaria kills over 400,000 people a year and new therapies are needed. Malaria parasites activate groups of genes by novel mechanisms that could be targeted by drugs. We will characterise a novel group of proteins to identify those that activate genes essential for parasite survival. We will also search for molecules that inhibit the proteins and kill malaria parasites. Thus we will discover how parasites control their genes and identify drug targets and inhibitors for drug development.
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.
Differential Regulation Of Endometrial Gene Expression In Endometriosis And Disease Subtypes
Funder
National Health and Medical Research Council
Funding Amount
$163,276.00
Summary
The endometrium or tissue lining the inside of the uterus is important in implantation and pregnancy, and is implicated in diseases including endometriosis. This project aims to use RNA sequencing to provide a detailed picture of gene expression in the endometrium and combine these results with our existing data to examine genetic control of gene regulation around the time of implantation and in regions of the genome associated with endometriosis and other diseases.
Working Towards A New Therapy For The Prevention Of Restricted Fetal Growth
Funder
National Health and Medical Research Council
Funding Amount
$711,356.00
Summary
If a baby does not grow properly during pregnancy there can be serious health problems when it is born. We also know that small babies have life long risks of poorer health. We have no effective therapies for improving a baby's growth. This application aims to discover a treatment that can help babies grow. This would be an important advance in improving the health of our future Australians.
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.
Identification Of The Conformation Dependant Targets Of Autoimmune Disease Linked Variation In Human Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,001,815.00
Summary
Specialised immune cells called regulatory T cells act as the policemen of the immune system, preventing the immune system attacking itself, but still fighting infections. If these cells do not work properly, autoimmune diseases such as type 1 diabetes or IBD can arise, because of immune attack on normal body tissue by mistake. In order to explain how this goes wrong we need to carefully identify all of the gene interactions in these cells including interactions over long distances in the DNA.
Natural Treg are dependent on the transcription factor FOXP3, but the mechanism of action of FOXP3 is only now becoming defined for human Treg. Tregs are critical for a balanced, responsive immune system, and deviation from this balance results in autoimmune diseases or persistence of cancers. In order to intervene to treat these disease it is essential to first know what makes a normal Treg function, and to then compare this with the disease so that faulty genes can be targeted for intervention ....Natural Treg are dependent on the transcription factor FOXP3, but the mechanism of action of FOXP3 is only now becoming defined for human Treg. Tregs are critical for a balanced, responsive immune system, and deviation from this balance results in autoimmune diseases or persistence of cancers. In order to intervene to treat these disease it is essential to first know what makes a normal Treg function, and to then compare this with the disease so that faulty genes can be targeted for intervention with new drugs or a cell therapy.Read moreRead less