Chromatin Dynamics As A Driver Of Disease Initiation And Development
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Epigenetic programming ensures that the right genes are expressed in the right amount, in the right cell type at the right time. Our OVERALL AIM is to identify how this programming is altered in certain cancers and dementias and to determine whether this is a cause or driver of disease. This study has great potential to identify the epigenetic marks that will be the best targets for new therapies.
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.
Organisation Of The Genome During The Development Of Antibody-secreting Cells
Funder
National Health and Medical Research Council
Funding Amount
$886,155.00
Summary
Each cell of our body contains over two metres of DNA that must be correctly packaged in order for our cells to function. We are using cutting-edge molecular biology techniques to study how this DNA circuitry is established in the white blood cells of our immune system that produce antibodies. Our novel approaches will reveal unique strategies to modulate immune responses to our benefit.
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.
This proposal uses the zebra fish system, which it is uniquely suited to investigate the regulation of disease genes. In all of these diseases preliminary work has already been performed and screening assays have been developed in a previous project (ZF-MODELS). In addition, the project will investigate genetic abnormalities of the eye and visual processing, genetic pathways underlying tissue regeneration and repair, and homologs of human genes related to diabetes and obesity, as well as infecti ....This proposal uses the zebra fish system, which it is uniquely suited to investigate the regulation of disease genes. In all of these diseases preliminary work has already been performed and screening assays have been developed in a previous project (ZF-MODELS). In addition, the project will investigate genetic abnormalities of the eye and visual processing, genetic pathways underlying tissue regeneration and repair, and homologs of human genes related to diabetes and obesity, as well as infectious disease and cancer. The Australian component will perform a systematic characterisation of enhancer elements of potential disease genes. This characterisation will build on the concept of genomic regulatory blocks (GRBs) which contain highly conserved non-coding elements (HCNEs) acting as long-range enhancers of developmental genes (recently discovered by T. Becker in the ZF-MODELS project).Read moreRead less
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.