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.
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 .
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.
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.
Four Dimensional Epigenome Remodelling: Implications For Endocrine Resistance In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$828,560.00
Summary
Patients with estrogen receptor positive breast cancer receive endocrine therapy, however half fail to respond and relapse. Endocrine resistant breast cancer currently represents the most significant challenge to breast cancer treatment. We suggest that three-dimensional epigenetic remodelling is an underlying mechanism that determines endocrine sensitivity that we will exploit as a novel therapeutic strategy to effectively treat patents with recurrent disease.
The Role Of Nuclear Architecture In The DNA Damage Response
Funder
National Health and Medical Research Council
Funding Amount
$561,966.00
Summary
The goal of the proposed research is to understand how dynamic changes to the chromatin genome packaging network, interact with the DNA damage response and gene expression machinery, to repair damaged DNA and the impact this has on cancer biology. To do so we are combining cutting edge molecular biology techniques with innovative novel microscopy methods developed by our research team, that far exceed the spatiotemporal resolution currently used to study chromatin biology.
ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the ....ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the whole genome as large inserts in BAC vectors, and build a "golden path" with minimal overlap. We will construct libraries of expressed genes from tammar tissues and array them for use in analysing gene expression.Read moreRead less
The Social Life of Death. This project aims to investigate experiences of death, dying and bereavement amidst rapid social, economic and political transformation. In the wake of COVID19, and as Australia’s anticipated ‘death boom’ approaches, how to foster good deaths has never been more uncertain, nor more urgent. Drawing on innovative methods and socio-cultural theory, and working in partnership with families and communities, this project aims to generate new knowledge to better inform and imp ....The Social Life of Death. This project aims to investigate experiences of death, dying and bereavement amidst rapid social, economic and political transformation. In the wake of COVID19, and as Australia’s anticipated ‘death boom’ approaches, how to foster good deaths has never been more uncertain, nor more urgent. Drawing on innovative methods and socio-cultural theory, and working in partnership with families and communities, this project aims to generate new knowledge to better inform and improve policy and spark cultural renewal around the end of life. Expected outcomes include setting the international benchmark for novel scholarly understandings of death, dying and bereavement, and centring community voices in addressing contemporary challenges to dying well.
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Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. Inte ....Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. International attention has already resulted in genome characterization of Australian icons (wallaby, Tasmanian devil and platypus), more research on these, and other Australian animals, will further highlight the importance of Australian fauna and impact positively on our scientific profile.Read moreRead less
Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a mo ....Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a model for epigenetic change, and sex chromosomes, which has engaged some of the greatest genetic minds over nearly a century. Therefore my results will attract wide international interest and impact positively on Australia's scientific profile, and further highlight the importance of Australian mammals.Read moreRead less