Therapeutic Targeting Of The Colorectal Cancer Epigenome
Funder
National Health and Medical Research Council
Funding Amount
$537,045.00
Summary
Enhancer RNAs (eRNAs) are a new class of noncoding RNA molecules that have been linked to diverse functions that impinge on cancer, but their clinical relevance is unknown. Our work shows that distinct eRNAs are expressed in a subset of cancer and predict which cancer will respond to a cancer therapeutic agent called a BET inhibitor. Our proposal uses sophisticated preclinical models and cutting edge technology to investigate the functional role of enhancers and enhancer templated RNA in cancer.
We have identified genetic abnormalities in 5% of breast cancers that fall in a novel DNA element called BIME1. This proposal aims to determine whether these genetic abnormalities contribute to breast tumourigenesis and which genes and pathways are affected by these mutations. The outcomes of this proposal may lead to the development of novel therapies for breast cancer or could influence the choice of existing therapies for patients that harbour these genetic abnormalities.
Understanding And Manipulating Long-range DNA Looping In Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$351,025.00
Summary
The turning on and off of genes often involves physical interactions between the gene and other parts of the DNA that lie far away from the gene. Disruption of this gene regulation is likely to contribute to a wide range of diseases, including heart disease and cancer. This project seeks to better understand the complex puzzle of how the correct DNA connections are chosen over the large number of possible mis-connections, by trying to find the fundamental laws that control DNA-DNA interactions.
Investigating The Molecular Signature Of ASD Through Integrative Genomics
Funder
National Health and Medical Research Council
Funding Amount
$621,128.00
Summary
Autism is the most severe end of a spectrum of neurodevelopmental conditions, autism spectrum disorders (ASD). We have identified a signature of genes dysregulated in the brain of autistic individuals. The proposed project will investigate how the molecular signature of autism is regulated in the brain, and whether genetic variants in regulatory DNA contribute to the genetic architecture of ASD.
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.
Functional Analysis Of Breast Cancer Susceptibility Regions
Funder
National Health and Medical Research Council
Funding Amount
$790,588.00
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.
Defining The Role Of A Novel Transcriptional Enhancer Element In Regulation Of Prox1 Expression And Endothelial Cell Identity.
Funder
National Health and Medical Research Council
Funding Amount
$706,909.00
Summary
The precise spatial and temporal control of gene expression is regulated by non-coding regions of the genome termed enhancers. Enhancers are crucial to program cell identity and have established roles in development and disease. We have identified a novel enhancer that we hypothesise controls the identity of valve endothelial cells by regulating expression of a master programmer of lymphatic endothelial cell identity, PROX1. Here we will investigate the role of this enhancer during development.
BEYOND TRADITIONAL GENE BOUNDARIES: Establishing The Importance Of Enhancer Epigenetic Reprogramming And Atypical Long-range Interactions In Cancer Cells.
Funder
National Health and Medical Research Council
Funding Amount
$718,515.00
Summary
Effective prevention and treatment strategies for cancer are still needed to combat this disease. By determining how DNA is packaged differently in prostate cancer cells relative to normal prostate cells, will allow us to understand how the specific location of regulatory centres or factories affects gene behavior. Unlike genetic defects in cancer, physical and chemical modifications to DNA in these centres are potentially reversible, providing an opportunity to develop novel therapeutics and di ....Effective prevention and treatment strategies for cancer are still needed to combat this disease. By determining how DNA is packaged differently in prostate cancer cells relative to normal prostate cells, will allow us to understand how the specific location of regulatory centres or factories affects gene behavior. Unlike genetic defects in cancer, physical and chemical modifications to DNA in these centres are potentially reversible, providing an opportunity to develop novel therapeutics and diagnostic tools.Read moreRead less