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.
Uncovering The Epigenetic Landscape That Regulates Human Transcriptional Memory
Funder
National Health and Medical Research Council
Funding Amount
$708,208.00
Summary
The ‘T cells’ in our bodies develop a memory of previous infections so that we do not become ill from them again. However, we do not fully understand how this memory works and it fails as we get old. We will use cutting-edge techniques to examine the detailed molecular wiring that ‘remembers’ viruses and see how it changes over time. This is hoped to facilitate the design of new age-specific vaccines and drugs and promote a more personalised approach to preventing and treating immune diseases.
Deciphering The Hallmarks Of Transcriptional Memory In Human T Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$511,316.00
Summary
The immune system works by using powerful cellular weapons, such as memory T cells, to protect us from disease. Remarkably, memory T cells are not only able to remember their first encounter, but by learning are able to make genes respond faster upon re-exposure to the pathogen. This proposal aims to determine the molecular tags that mark genes in human memory T cells. Given the current global health challenges of devising effective vaccines, this will be critical for future disease therapy.
Epigenetic Regulation By Lysine Specific Demethylases In Breast Cancer Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$590,860.00
Summary
The factors behind breast cancer recurrence are not fully understood but it is becoming increasingly evident that the spread of primary cancer can be initiated at a very early stage of cancer development by a small population of unique cancer cells, termed cancer stem cells (CSCs). Targeting of these CSCs has emerged as a priority area in cancer therapy. Our aim is to demonstrate that a novel class of epigenetic enzymes are key molecular targets of CSCs and propose a strategy to eradicate CSCs.
Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
The Role Of Moz, An Epigenetic Regulator, In The Pathogenesis Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$713,872.00
Summary
We are studying the oncogene and epigenetic regulator MOZ, (monocytic leukaemia zinc finger protein), with the aim firstly of better understanding the pathogenesis of cancer and secondly developing a new class of anti-cancer drugs.
The Special Role Of Histone Variants In Regulating The Inheritance And 3-dimensional Organisation Of The Epigenome
Funder
National Health and Medical Research Council
Funding Amount
$962,716.00
Summary
It has been more than a decade since the human genome has been completely sequenced but how this genomic information is selectively utilized to direct gene expression that is unique to each of the 200 different cell types of the human body remains to be elucidated. We have new data to suggest that it is how our genome is packaged into a variety of different and dynamic 3-dimensional structures in a cell that determines cell type specific programs of gene expression
A New Paradigm For The Control Of Cellular Function: The Dynamic Reshaping Of The Epigenome By Histone Variants
Funder
National Health and Medical Research Council
Funding Amount
$672,735.00
Summary
Our DNA is packaged and partitioned into stable identities, chromosomes, which is critical for proper cell function and the inheritance of our genetic material from one cell generation to the next. Loss of chromosome integrity leads to cancer and therefore the cell must ensure that this does not happen. We have uncovered a new mechanism whereby different components of chromosomes can dynamically move from one location to another to ensure chromosomes remain stable when they are challenged.
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.
Regulation Of Ribosomal RNA Gene Chromatin During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$882,486.00
Summary
The overarching goal of this proposal is to determine the molecular basis for tumour cell dependence on activated ribosomal RNA gene repeats (rDNA). Our working model posits that rDNA repeats become activated through changes in rDNA chromatin structure that include increased binding of the RNA Polymerase I transcription factor UBF.