Epigenetic Therapies As Molecular Probes To Investigate The Molecular Pathogenesis Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$937,402.00
Summary
A major limitation to the success of targeted therapies in cancer is the fact that we have few if any tools to study in detail their mechanism of action within cancerous and normal cells. If we were able to visualise these drugs within cells and precisely characterise the proteins, DNA and RNA within a cell that interact with these therapies we will be able to identify strategies that can optimise their efficacy and reduce the side-effects of these treatments.
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.
Identification Of Novel Mechanisms Governing Stage-specific Regulation Of The Human Globin Genes
Funder
National Health and Medical Research Council
Funding Amount
$481,826.00
Summary
Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases worldwide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing embryo, fetal hemoglobin. We have identified key factors important for fetal gene expression. Our goal is to translate these findings into therapies for the hemoglobin disorders.
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
New Insights on Modelling Time Trends with Panel Data: Theory and Practice. This project aims to tackle important challenges in time trend modelling by taking advantage of panel data structures. This project expects to propose flexible models in time trend modelling to retrieve reliable inference. The expected outcomes include innovative econometric models and methods that have a wide range of applications, and are particularly suited for empirical problems within large and complex systems. This ....New Insights on Modelling Time Trends with Panel Data: Theory and Practice. This project aims to tackle important challenges in time trend modelling by taking advantage of panel data structures. This project expects to propose flexible models in time trend modelling to retrieve reliable inference. The expected outcomes include innovative econometric models and methods that have a wide range of applications, and are particularly suited for empirical problems within large and complex systems. This will provide significant benefits to all fields in which data displays any form of trending behaviour. The proposed model is used to evaluate the economic consequences of climate change and global housing market contagion, which provide strong evidence-based insights to the environmental and economic policies in Australia.Read moreRead less
Constrained and Stable Solutions of Nonlinear and Semismooth Equations. In this project, comprehensive models for designing safe power system parameters will be proposed, efficient algorthms for solving these models will be constructed. The new models and algorithms in this project will provide efficient tools to prevent catastrophic events in power systems, which is related with national security. This project will also strengthen collaboration of Australian applied
mathematians with inter ....Constrained and Stable Solutions of Nonlinear and Semismooth Equations. In this project, comprehensive models for designing safe power system parameters will be proposed, efficient algorthms for solving these models will be constructed. The new models and algorithms in this project will provide efficient tools to prevent catastrophic events in power systems, which is related with national security. This project will also strengthen collaboration of Australian applied
mathematians with international researchers and engineering scientists. This is important for the advance of science and technology in
Australia.Read moreRead less
Computational modelling of nanofluids for industrial applications. The use of nanoparticles in heat transfer fluids, then known as nanofluids, increases their specific heat and thermal conductivity. Recent experimental works highlight that anomalous transport phenomena are evident in nanofluids that cannot be adequately described by classical conservation laws. We will extend these conservation laws to incorporate fractional operators to capture the fluid memory effects and the impact of particl ....Computational modelling of nanofluids for industrial applications. The use of nanoparticles in heat transfer fluids, then known as nanofluids, increases their specific heat and thermal conductivity. Recent experimental works highlight that anomalous transport phenomena are evident in nanofluids that cannot be adequately described by classical conservation laws. We will extend these conservation laws to incorporate fractional operators to capture the fluid memory effects and the impact of particle clustering. Computational modelling and experimental investigations will be undertaken to identify the heat transfer mechanisms of various nanofluids. The outcomes of the work will increase knowledge on nanofluids and offer a significant opportunity to improve the efficiency of many thermal engineering systems.Read moreRead less
Identification and inference in nonparametric models. This project will develop reliable methods for identification, estimation and inference of nonparametric models for the evaluation of economic policies on outcome variables of interest. This econometric methodology will allow a better understanding of the quantitative effects of an economic policy which will result in better informed policy decisions. The results will have applications to labour market policies, health care policies and educa ....Identification and inference in nonparametric models. This project will develop reliable methods for identification, estimation and inference of nonparametric models for the evaluation of economic policies on outcome variables of interest. This econometric methodology will allow a better understanding of the quantitative effects of an economic policy which will result in better informed policy decisions. The results will have applications to labour market policies, health care policies and education policies among others. The project will also provide national benefits in terms of building up the local stock of researchers trained in the area of identification and estimation of nonparametric models; it will further improve the international reputation that Australia has in econometric theory.Read moreRead less
Dynamics of eigenvalue/eigenspace algorithms with applications to signal processing. Many problems in signal and systems lead naturally to an eigenvalue/eigenspace determination and tracking problem; for example (acoustic) echo-cancellation, crosstalk suppression in ADSL modems, direction of arrival determination with an array of sensors, linear system identification etc. Exploiting methods from global analysis and dynamical systems theory we will study the available algorithms for eigenspace de ....Dynamics of eigenvalue/eigenspace algorithms with applications to signal processing. Many problems in signal and systems lead naturally to an eigenvalue/eigenspace determination and tracking problem; for example (acoustic) echo-cancellation, crosstalk suppression in ADSL modems, direction of arrival determination with an array of sensors, linear system identification etc. Exploiting methods from global analysis and dynamical systems theory we will study the available algorithms for eigenspace determination to characterise their computational efficiency, accuracy and effectiveness in various data scenarios. The analysis will lead to improved designs for eigenvalue/eigenspace algorithms, as well as design tools to engineer algorithms to specific situations.Read moreRead less