Ubiquitin And SUMO DNA Damage Response Signalling At Deprotected Telomeres During The Cell Cycle
Funder
National Health and Medical Research Council
Funding Amount
$302,627.00
Summary
Following genome damage cells stop the cell division process and initiate DNA repair. We discovered that at specific times during cell division his does not happen if the damage signals originate from the chromosome ends (i.e. “telomeres”). We anticipate this is necessary to prevent genomic instability in healthy cells and may be driving genomic instability in cancer cells. Experiments described here will elucidate the molecular mechanisms and biological significance of our observation.
Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collecti ....Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collection of structure restraints by nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and mass spectrometry, which are needed to generate accurate models of proteins and their complexes with other molecules. Major beneficial outcome will include an increase in the number of protein targets amenable to rational drug design and improved methods for generating new drug leads.Read moreRead less
Mitochondrial targeting by a new class of gadolinium agents. This research project will lead to the development of new molecular agents containing the element gadolinium which can selectively accumulate within cell mitochondria, with a long-term application in cutting-edge therapies involving X-rays or neutrons. The lanthanoid element gadolinium offers many unique opportunities for medicinal chemistry and this project will generate new knowledge in bioinorganic chemistry and synchrotron science. ....Mitochondrial targeting by a new class of gadolinium agents. This research project will lead to the development of new molecular agents containing the element gadolinium which can selectively accumulate within cell mitochondria, with a long-term application in cutting-edge therapies involving X-rays or neutrons. The lanthanoid element gadolinium offers many unique opportunities for medicinal chemistry and this project will generate new knowledge in bioinorganic chemistry and synchrotron science. The expected outcomes of this research will address many of the unresolved questions regarding mitochondrially-targeted gadolinium complexes, the first such agents specifically designed for potential long-term application in binary therapies and imaging.Read moreRead less
New frontiers in the therapeutic application of gadolinium. This research involves the design and development of new anticancer agents that will dramatically expand the clinical efficacy of a promising treatment for highly aggressive tumours. The innovative nature of this research will also contribute to Australia's science knowledge base and provide excellent training in the area of drug discovery.
Group 13 Mixed Halide-Hydride and Rare Earth Complexes - New Selective Chiral Hydridic or Low Valent Reducing Agents. This project will make a landmark contribution to two areas of metallohydride chemistry. Both studies will utilise and develop metals that have traditionally been mined and exported from these shores while concurrently imported as value added products at vastly inflated cost. This research will identify knock-on applications in order to stem this financial bias. The new paths to ....Group 13 Mixed Halide-Hydride and Rare Earth Complexes - New Selective Chiral Hydridic or Low Valent Reducing Agents. This project will make a landmark contribution to two areas of metallohydride chemistry. Both studies will utilise and develop metals that have traditionally been mined and exported from these shores while concurrently imported as value added products at vastly inflated cost. This research will identify knock-on applications in order to stem this financial bias. The new paths to rare earth (= Ln) hydrides will have broad industrial appeal, particularly for new materials, where, like similar group 13 materials, they may be used in the deposition of Ln films or even as precursors to superconducting solids. It is anticipated industrial collaboration will ensue. Australia will be promoted as a developer and innovator of frontier technologies.Read moreRead less
Enhancing single-molecule magnets. This project aims to design, synthesise and investigate single-molecule magnets that can function at higher temperatures for use in quantum computing and molecular spintronics. Materials science increasingly benefit from molecular approaches, and lanthanoid-based single-molecule magnets could achieve otherwise inaccessible technological developments such as the development of molecular materials for quantum computing and molecular spintronics. Advances in funda ....Enhancing single-molecule magnets. This project aims to design, synthesise and investigate single-molecule magnets that can function at higher temperatures for use in quantum computing and molecular spintronics. Materials science increasingly benefit from molecular approaches, and lanthanoid-based single-molecule magnets could achieve otherwise inaccessible technological developments such as the development of molecular materials for quantum computing and molecular spintronics. Advances in fundamental chemistry are anticipated, and this project is expected to benefit Australia's participation in related high-end technology industries.Read moreRead less
Charge-Controlled Materials for Separations of Important Resources. This project aims to develop new porous materials that are capable of greater molecular discrimination than current technologies. This project expects to advance understanding of fundamental structure-activity relationships in these materials, and synthetic targets will be geared towards materials for industrially or environmentally important chemical separations associated with metal extraction. Expected outcomes of this projec ....Charge-Controlled Materials for Separations of Important Resources. This project aims to develop new porous materials that are capable of greater molecular discrimination than current technologies. This project expects to advance understanding of fundamental structure-activity relationships in these materials, and synthetic targets will be geared towards materials for industrially or environmentally important chemical separations associated with metal extraction. Expected outcomes of this project include new insights on the underlying chemistry for tailoring crystalline microporous materials towards select applications. This should provide significant benefits, such as future low-energy and efficient technologies for industrially important separation processes with reduced financial and environmental costs.Read moreRead less
Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interaction ....Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interactions and be used as lead compounds for treatments for disease.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101652
Funder
Australian Research Council
Funding Amount
$434,404.00
Summary
Assessing climate risk for future food supply. The aim of this project is to assess the impacts of future disruptive climate events and disasters on Australia's food system. This will be achieved by developing a world-first Integrated Assessment Modelling Lab, a collaborative research platform for comprehensive assessment of the effects of extreme climate events (bushfires/drought/floods/cyclones) on Australia's food supply. The project will use this capability to assess impacts on Australia's n ....Assessing climate risk for future food supply. The aim of this project is to assess the impacts of future disruptive climate events and disasters on Australia's food system. This will be achieved by developing a world-first Integrated Assessment Modelling Lab, a collaborative research platform for comprehensive assessment of the effects of extreme climate events (bushfires/drought/floods/cyclones) on Australia's food supply. The project will use this capability to assess impacts on Australia's national and international supply chains, industry sectors and on socio-economic groups. The outcomes will offer opportunities to improve national responses to the changing climate and build resilience by designing adaptation plans to safeguard national and international food supply chains.Read moreRead less
The role of the transcription factor Runx2 during mammary gland development and lactation. This proposal will further our understanding of mammary gland development and lactation and the mechanisms controlling mammary cell fate decisions such as differentiation. Regulation of cell fate lies at the core of most aspects of cell biology from normal development to dysfunction such as cancer. The knowledge gleamed from this project also has the potential to make economic gains for Australia by increa ....The role of the transcription factor Runx2 during mammary gland development and lactation. This proposal will further our understanding of mammary gland development and lactation and the mechanisms controlling mammary cell fate decisions such as differentiation. Regulation of cell fate lies at the core of most aspects of cell biology from normal development to dysfunction such as cancer. The knowledge gleamed from this project also has the potential to make economic gains for Australia by increasing the profitability and ensuring the sustainability of both the dairy and meat industries. Better understanding of the mechanisms controlling mammary epithelial cell differentiation should enable augmentation of lactation such as increasing milk protein content, using marker assisted selection (of targets such as Runx2) in cattle.Read moreRead less