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 .
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.
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.
Group orbits in garmonic analysis and ergodic theory. Researchers from many areas need a type of mathematical analysis which involves the behaviour of a system - which may be a set of data points - under repeated application of some operation or group of operations. The structures arising from this kind of process are known as group orbits. The project gives information about their nature. Two major types of orbits are considered, coming from actions of discrete groups on measure spaces, and fro ....Group orbits in garmonic analysis and ergodic theory. Researchers from many areas need a type of mathematical analysis which involves the behaviour of a system - which may be a set of data points - under repeated application of some operation or group of operations. The structures arising from this kind of process are known as group orbits. The project gives information about their nature. Two major types of orbits are considered, coming from actions of discrete groups on measure spaces, and from smooth actions of Lie groups on manifolds, where powerful geometric methods are available. The project will yield new understandings of entropy, and new approaches to Fourier analysis.Read moreRead less
Ergodic theory and number theory. Recent advances in the theory of measured dynamical systems investigated by the proponents include new versions of entropy, and the study of spectral theory for non-singular systems. These will be further developed in this joint project with the French CNRS. The results are expected to have interesting applications in physics and number theory.
Entropy and maximal entropy in Markov systems. Entropy is a measure of how well-ordered a system is: chaotic systems have high entropy. Two approaches to entropy are available, via the limiting behaviour of the orbits of points, which yields topological entropy, and via the behaviour of the distributions of measures of partitions, yielding measure-theoretic entropy. The topological entropy is the least upper bound of entropies of all possible measures. We study when there is a measure which real ....Entropy and maximal entropy in Markov systems. Entropy is a measure of how well-ordered a system is: chaotic systems have high entropy. Two approaches to entropy are available, via the limiting behaviour of the orbits of points, which yields topological entropy, and via the behaviour of the distributions of measures of partitions, yielding measure-theoretic entropy. The topological entropy is the least upper bound of entropies of all possible measures. We study when there is a measure which realises this bound, describing the structure of such systems via Markov and Bratteli diagrams. Our methods will be applied to new versions of entropy for non-singular systems. This will assist in the description of chaotic behaviour.Read moreRead less
Symmetries in analysis. Technical research is like an iceberg. The 10% you see in applications is supported by 90% hidden, long-term, sometimes abstruse or theoretical-sounding work. The area of mathematical analysis has, for over 200 years, proved its worth as part of the unseen 90%, giving us such important tools as Fourier analysis, statistical mechanics and quantum mechanics. Australia is known as a world leader in mathematical analysis, and it is important for the country to maintain that e ....Symmetries in analysis. Technical research is like an iceberg. The 10% you see in applications is supported by 90% hidden, long-term, sometimes abstruse or theoretical-sounding work. The area of mathematical analysis has, for over 200 years, proved its worth as part of the unseen 90%, giving us such important tools as Fourier analysis, statistical mechanics and quantum mechanics. Australia is known as a world leader in mathematical analysis, and it is important for the country to maintain that edge in a number of key disciplines, so we can continue to participate in global technological advance. The project has an international focus which will enable that to happen. It will also provide training for the next generation of mathematicians. Read moreRead less