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.
Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably e ....Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably extend the information potential of the genetic code. In addition, it is now established that chromatin structural features can influence gene expression. In vitro studies support a model in which chromatin functions as a barrier for the access to DNA. Therefore this organization has to be tighly regulated and dynamic to allow the protein-DNA interactions critical for nuclear functions. Importantly genome organisation provides in addition to genetic information another layer of information, so called epigenetic, which by definition means that it is stably inherited throughout cellular divisions, yet it is not encoded genetically. Thus each cell type will display a specific epigenome. We have recently constructed small human minichromosomes, which are much easier to study than the much larger normal chromosomes. The present project proposes to define the epigenetic feature across an entire human chromosome using our minichhromosomes as working models. The outcome will be a significant gain in our knowledge on the processes underlying epigenetic regulation, the organisation of specialised chromatin domain, and behaviour of the chromosomes.Read moreRead less
HARMONIC ANALYSIS AND BOUNDARY VALUE PROBLEMS FOR ELLIPTIC SYSTEMS. It is of the utmost necessity for Australia to develop the theoretical
expertise needed in the current era. The type of mathematics under
investigation here is closely allied to that needed in much of the
current boom in communication technology and medical research. The
training which would be provided to the research associates is
considerable, and would flow on to produce the expertise needed to
keep the coming gen ....HARMONIC ANALYSIS AND BOUNDARY VALUE PROBLEMS FOR ELLIPTIC SYSTEMS. It is of the utmost necessity for Australia to develop the theoretical
expertise needed in the current era. The type of mathematics under
investigation here is closely allied to that needed in much of the
current boom in communication technology and medical research. The
training which would be provided to the research associates is
considerable, and would flow on to produce the expertise needed to
keep the coming generation involved in modern technological development. I will maintain my large collaborative effort with
leading mathematicians from the US, France and other countries, thus
helping to keep Australia at the forefront of a significant field of
research.Read moreRead less
HARMONIC ANALYSIS OF ELLIPTIC SYSTEMS ON RIEMANNIAN MANIFOLDS. It is of the utmost necessity for Australia to develop the theoretical expertise needed in the current era. The type of mathematics under investigation here is closely allied to that needed in much of the current boom in communication technology and medical research. The training which would be provided to the research associates is considerable, and would flow on to produce the expertise needed to keep the coming generation invol ....HARMONIC ANALYSIS OF ELLIPTIC SYSTEMS ON RIEMANNIAN MANIFOLDS. It is of the utmost necessity for Australia to develop the theoretical expertise needed in the current era. The type of mathematics under investigation here is closely allied to that needed in much of the current boom in communication technology and medical research. The training which would be provided to the research associates is considerable, and would flow on to produce the expertise needed to keep the coming generation involved in modern technological development. I will maintain my active collaborative effort with leading mathematicians from the US, France and other countries, thus helping to keep Australia at the forefront of a significant field of research.Read moreRead less
Propagation of singularities for the Schrodinger equation. The time-dependent Schrodinger equation governs the evolution of quantum particles. In this project we aim to use new techniques from mathematical scattering theory to analyse solutions of the Schrodinger equation and obtain sharp bounds on their singularities. Controlling such singularities will allow us to deduce quantitative bounds on the number of eigenvalues in certain situations, and provide new techniques for studying nonlinear Sc ....Propagation of singularities for the Schrodinger equation. The time-dependent Schrodinger equation governs the evolution of quantum particles. In this project we aim to use new techniques from mathematical scattering theory to analyse solutions of the Schrodinger equation and obtain sharp bounds on their singularities. Controlling such singularities will allow us to deduce quantitative bounds on the number of eigenvalues in certain situations, and provide new techniques for studying nonlinear Schrodinger equations. Read moreRead less
Physics of Risk: new tools to survey the Australian market and beyond. The lives of most Australians depend on the dynamics of financial markets that affects investments, savings, business, employment, growth, wealth and -ultimately- the daily functioning of our society. Understanding, monitoring and managing the dynamics of financial markets is of crucial importance to policy-makers, financial institutions and businesses that are increasingly faced with managing risk, planning strategies and ta ....Physics of Risk: new tools to survey the Australian market and beyond. The lives of most Australians depend on the dynamics of financial markets that affects investments, savings, business, employment, growth, wealth and -ultimately- the daily functioning of our society. Understanding, monitoring and managing the dynamics of financial markets is of crucial importance to policy-makers, financial institutions and businesses that are increasingly faced with managing risk, planning strategies and taking decisions in an increasingly complex market-place. The project is also of importance to the continued evolution of physics in this country contributing to the emergence of a strong new area of statistical physics concerned with the ?real world? in a manner hitherto unknown.Read moreRead less
HARMONIC ANALYSIS, BOUNDARY VALUE PROBLEMS, AND MAXWELL'S EQUATIONS IN LIPSCHITZ DOMAINS. Boundary value problems for partial differential equations arise naturally when physical problems are expressed in mathematical terms. This project concerns the systematic development of the harmonic analysis of partial differential operators, and of the corresponding boundary integrals in order to solve such problems on irregular regions. Particular emphasis is given to studying the behaviour of electrom ....HARMONIC ANALYSIS, BOUNDARY VALUE PROBLEMS, AND MAXWELL'S EQUATIONS IN LIPSCHITZ DOMAINS. Boundary value problems for partial differential equations arise naturally when physical problems are expressed in mathematical terms. This project concerns the systematic development of the harmonic analysis of partial differential operators, and of the corresponding boundary integrals in order to solve such problems on irregular regions. Particular emphasis is given to studying the behaviour of electromagnetic waves both inside and outside irregularly shaped surfaces, and their propagation through it.Read moreRead less
Harmonic analysis of differential operators in Banach spaces. This proposal aims to develop harmonic analysis (the mathematical tools used in digital music and photography) in new contexts. It focuses on boundary value problems (the theory behind medical or geological imaging) and stochastic equations (which describe phenomena with random components such as the behaviour of financial markets).