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.
H2A.Z Acetylation: Deregulation Of Enhancer Activity And 3D Chromatin In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$859,350.00
Summary
DNA is not linear but packaged in the cell nucleus in a three-dimensional (3D) structure in such a way that distal regulatory regions can interact to control gene expression. Our new data suggests that a chemical modification of the histone variant H2A.Z plays a critical role in the formation of the 3D chromatin structure. This project is aimed to dissect the role of H2A.Z in prescribing 3D structure, which will provide a more precise understanding of gene deregulation in cancer.
Structure And Function Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$1,282,475.00
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.
Understanding How Defects In Chromosome Structure Can Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$546,557.00
Summary
The correct folding of DNA is critical to a cell's survival. This is orchestrated by a special class of proteins called the condensins. Defects in condensin lead to aberrant chromosome folding and disease. We aim to understand how condensin folds chromosomes and why mutations in condensin are increasingly associated with disease.
Understanding The Role Of Chromosome Condensation Proteins And Their Link To Disease
Funder
National Health and Medical Research Council
Funding Amount
$601,224.00
Summary
Cells divide through a complex cascade of signals from our genetic material (DNA) which need to be finely tuned for events to occur properly. Errors in control cause faulty cell division and lead to diseases such as cancer. We have identified a master controller of these events termed the condensin complex and aim to understand how it orchestrates these functions by creating a map of its DNA location and understanding which regions in the genetic material it controls and how.
Identifying Novel Long-noncoding RNAs Involved In The Development Of Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$785,204.00
Summary
Recent studies have identified regions within the human genome in which DNA sequence variations are associated with an increased risk of breast cancer. The aim of this proposal is to identify and characterise these non-coding genes that are modulate breast cancer risk. Understanding how sequences variations that alter these novel genes contribute to breast cancer will provide novel avenues for therapy.
CTCF is a unique architectural protein that regulates the three-dimensional (3D) folding of the genome to switch our genes on, or off. This is important, as it affects how DNA is arranged inside the cells, which is turn assures correct gene expression patterns. Here, we will define the role of CTCF in organizing the 3D genome architecture and identify genetic and epigenetic states that control its function.
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.
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.
Role Of Epigenetic Modifyers MBD2 And TET Proteins In DNA Methylation And Demethylation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$722,068.00
Summary
Cancer is a disease of both genetics and epigenetics, the cell machinery that controls how the DNA code is read. DNA methylation is one part of epigenetics but few studies have investigated how the loss of methylation contributes to cancer formation. We have exciting new data that implicates specific proteins in this process and, with this funding we will determine how these proteins affect gene regulation in cancer, potentially leading to novel cancer diagnosis and treatment strategies.