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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.
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 .
ARC Centre of Excellence in Plant Cell Wall Biology. The ARC Centre for Plant Cell Wall Biology will define the regulatory mechanisms that control molecular, enzymic and cellular processes involved in the synthesis, deposition, re-modelling and depolymerisation of cell wall polysaccharides of cereals and grasses. Plant cell walls represent the world's largest renewable carbon resource, but the regulatory mechanisms responsible for their synthesis and assembly are not understood. Key distinguishi ....ARC Centre of Excellence in Plant Cell Wall Biology. The ARC Centre for Plant Cell Wall Biology will define the regulatory mechanisms that control molecular, enzymic and cellular processes involved in the synthesis, deposition, re-modelling and depolymerisation of cell wall polysaccharides of cereals and grasses. Plant cell walls represent the world's largest renewable carbon resource, but the regulatory mechanisms responsible for their synthesis and assembly are not understood. Key distinguishing features of the Centre will be the international, integrative, and multidisciplinary approach towards addressing major questions in plant biology, its strategy to leverage ARC funding, and its linkages with potential national and international end-users of the fundamental scientific discoveries.Read moreRead less
Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolu ....Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolution crystal structures are being used to identify function. Intriguingly, preliminary data indicates that the mutations do not affect the native antibody structure, but rather influence dynamic states. The project plans to use a combination of mutagenesis, molecular dynamics simulation and deuterium exchange to study antibody dynamics.Read moreRead less
Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine th ....Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine that controls whether or not the immune system becomes activated. Accordingly, this proposal will provide far-reaching insights into molecular events that are of central importance to the initiation of immunity, and thus will ultimately benefit society via improvements in health.Read moreRead less
Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell recept ....Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell receptor is determined by utilising structural biology and cellular immunology techniques. The impact of this project effects the development of innovative T cell immunomodulatory agents, improving the health and quality of life of the Australian population.Read moreRead less
Next generation high throughput lipidomics using adaptive modelling. This project aims to develop a unique high-throughput method to capture the lipidomic profile of human plasma suitable for large human population screening. Lipids are fundamental to every biological system, but our understanding of their regulation in humans have been largely superficial. By incorporating a new lipidomics approach, with genomic data, this project aims to expand our understanding of human biology by identifying ....Next generation high throughput lipidomics using adaptive modelling. This project aims to develop a unique high-throughput method to capture the lipidomic profile of human plasma suitable for large human population screening. Lipids are fundamental to every biological system, but our understanding of their regulation in humans have been largely superficial. By incorporating a new lipidomics approach, with genomic data, this project aims to expand our understanding of human biology by identifying regulators of lipid metabolism. The large diversity in humans necessitate sufficient sample sizes to identify true genetic regulators, but to date techniques capturing phenotypic data (lipids) have been largely limited. It is anticipated that this study will identify new regulators of lipid metabolism in humans.Read moreRead less
Special Research Initiatives - Grant ID: SR0354740
Funder
Australian Research Council
Funding Amount
$10,000.00
Summary
CaGaWaLo: regulation of carbon gain and water loss by woody vegetation. Trees and shrubs are widely perceived as central to solving problems of national and international significance. Seed funding is sought to facilitate establishment of a research network focused on their ability to sequester carbon and transmit water to the atmosphere. The proposed network is broadly based in plant physiology and ecology and contains a strong cross-section of leading international expertise in relevant sub- ....CaGaWaLo: regulation of carbon gain and water loss by woody vegetation. Trees and shrubs are widely perceived as central to solving problems of national and international significance. Seed funding is sought to facilitate establishment of a research network focused on their ability to sequester carbon and transmit water to the atmosphere. The proposed network is broadly based in plant physiology and ecology and contains a strong cross-section of leading international expertise in relevant sub-disciplines. By leveraging the huge pool of international expertise and focusing on a range of scales (from molecular to biosphere scales), this network will yield new ideas and approaches that will produce outputs and outcomes of national significance.Read moreRead less