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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE240100054
Funder
Australian Research Council
Funding Amount
$1,341,398.00
Summary
Dedicated High-throughput 3D-Electron Diffractometer. This proposal aims to install the first dedicated high-throughput 3D-electron diffractometer in the Southern Hemisphere, and one of the first in the world. It will be able to rapidly solve the atomic-scale structures of molecules and materials for which this is now extremely difficult and time-consuming – or impossible – due to the inability to grow large enough crystals for traditional X-ray diffraction. It will thus provide a significant ad ....Dedicated High-throughput 3D-Electron Diffractometer. This proposal aims to install the first dedicated high-throughput 3D-electron diffractometer in the Southern Hemisphere, and one of the first in the world. It will be able to rapidly solve the atomic-scale structures of molecules and materials for which this is now extremely difficult and time-consuming – or impossible – due to the inability to grow large enough crystals for traditional X-ray diffraction. It will thus provide a significant advantage for chemists, physicists, biologists, geologists, and engineers who rely on detailed structural knowledge to rationally optimise the properties of their compounds, from pharmaceutical activity to carbon capture to superconductivity, to the substantial benefit of multiple national priority areas.Read moreRead less
The impact of copper on protein turnover. This project aims to elaborate a novel discovery by the research team, that a conserved copper-binding site in a group of conserved conjugating enzymes promotes ubiquitination of a range of essential proteins leading to their rapid degradation, which might be a means of maintaining copper homeostasis. This project will employ a range of integrated physicochemical, biochemical and cell biology approaches to illuminate the molecular nature of this copper a ....The impact of copper on protein turnover. This project aims to elaborate a novel discovery by the research team, that a conserved copper-binding site in a group of conserved conjugating enzymes promotes ubiquitination of a range of essential proteins leading to their rapid degradation, which might be a means of maintaining copper homeostasis. This project will employ a range of integrated physicochemical, biochemical and cell biology approaches to illuminate the molecular nature of this copper action on the enzyme and its partners. Expected outcomes include an analytical understanding of the molecular mechanisms of this process, and enhanced interdisciplinary collaboration between experts. Potential benefits include new strategies to intervene in copper-related disorders of aging.Read moreRead less
How does the chromatin remodeller CHD4 regulate gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are in many ways still mysterious. It is well established that gene expression patterns in complex organisms are determined in part by the manner in which DNA is physically packaged. Our aim is to define new aspects of these mechanisms that revolve around molecular motors that regulate DNA packaging. This foundational knowled ....How does the chromatin remodeller CHD4 regulate gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are in many ways still mysterious. It is well established that gene expression patterns in complex organisms are determined in part by the manner in which DNA is physically packaged. Our aim is to define new aspects of these mechanisms that revolve around molecular motors that regulate DNA packaging. This foundational knowledge will deepen our understanding of gene regulation in all complex organisms and will inform future efforts to rationally modulate gene expression patterns in agriculture, research and other important areas.Read moreRead less
Asgard archaea: the first eukaryotic cells? . This project aims to uncover the role of unique microorganisms (Asgard archaea) in the origin of eukaryotes. These archaea may represent a ‘missing-link’ in eukaryotic evolution and are in abundance in the stromatolites in Shark Bay, Western Australia. Employing an innovative and interdisciplinary approach of cutting-edge molecular biology and high-resolution microscopy, this project expects to generate insights into fundamental aspects of evolution ....Asgard archaea: the first eukaryotic cells? . This project aims to uncover the role of unique microorganisms (Asgard archaea) in the origin of eukaryotes. These archaea may represent a ‘missing-link’ in eukaryotic evolution and are in abundance in the stromatolites in Shark Bay, Western Australia. Employing an innovative and interdisciplinary approach of cutting-edge molecular biology and high-resolution microscopy, this project expects to generate insights into fundamental aspects of evolution and cell biology. Expected outcomes include the discovery of unique branches of life and the proposal of new models for the emergence of eukaryotes. This research should allow for benefits across a spectrum of environmental and social gains, including improved ties with Indigenous communities.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230100837
Funder
Australian Research Council
Funding Amount
$441,454.00
Summary
Modulating protein phase behavior: cell functions vs material development. It has been recognized recently that cellular proteins can undergo liquid-liquid phase separation, however, a further liquid-to-solid transition can lead to aberrant biological processes. This project aims to investigate and control this behaviour to gain insights into cell dysfunction and new routes for biomaterials development. An integrated approach combining microfluidic platforms, optical techniques, and vibrational ....Modulating protein phase behavior: cell functions vs material development. It has been recognized recently that cellular proteins can undergo liquid-liquid phase separation, however, a further liquid-to-solid transition can lead to aberrant biological processes. This project aims to investigate and control this behaviour to gain insights into cell dysfunction and new routes for biomaterials development. An integrated approach combining microfluidic platforms, optical techniques, and vibrational spectroscopy will be exploited. Expected outcomes of this project include the mechanistic understanding of protein phase behaviour and protein-based biomaterial engineering. This should provide significant benefits in the prevention of aberrant protein aggregation and the generation of materials as plastic substitutes.Read moreRead less
In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-ski ....In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-skilled techniques, including cryo-electron microscopy and single-molecule imaging and holds ancillary benefits to postgraduate students. Anticipated outcomes include influential publications, building a critical mass of expertise in Australia and fostering international collaborations with Australia at the epicentre.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101536
Funder
Australian Research Council
Funding Amount
$473,824.00
Summary
How does heme regulate blood vessel formation in the brain? There are more than 600 kilometres of blood vessels in the brain, all of which are lined by tightly packed cells that protect the brain from toxins. My research aims to investigate how these blood vessels are formed. This project expects to reveal the role that a critical signalling molecule called heme plays in this fundamental biological process. I will use cutting-edge structural biology and biophysical techniques to uncover the mole ....How does heme regulate blood vessel formation in the brain? There are more than 600 kilometres of blood vessels in the brain, all of which are lined by tightly packed cells that protect the brain from toxins. My research aims to investigate how these blood vessels are formed. This project expects to reveal the role that a critical signalling molecule called heme plays in this fundamental biological process. I will use cutting-edge structural biology and biophysical techniques to uncover the molecular mechanisms that allow heme to enter cells and regulate blood vessel growth in the brain. The outcomes of this research will enhance our understanding of the brain’s core infrastructure and will contribute to an understanding of how cerebral blood vessels grow and maintain integrity. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100780
Funder
Australian Research Council
Funding Amount
$455,237.00
Summary
Functional and structural dissection of the human replisome. This project aims to develop technology to visualise the structure and enzymatic activities of the human replisome, the multiprotein assembly that copies DNA before cell division. A combination of novel single-molecule and state-of-the-art cryo-electron microscopy will be used to define how the human replisome coordinates DNA synthesis during times of replication stress. Key outcomes of this project include development of novel molecul ....Functional and structural dissection of the human replisome. This project aims to develop technology to visualise the structure and enzymatic activities of the human replisome, the multiprotein assembly that copies DNA before cell division. A combination of novel single-molecule and state-of-the-art cryo-electron microscopy will be used to define how the human replisome coordinates DNA synthesis during times of replication stress. Key outcomes of this project include development of novel molecular visualisation technologies, leading to the first molecular description of dynamic processes used by the human replisome. Benefits include improved understanding of a fundamental biological process that often malfunctions in cancers, development of novel methodology, and interdisciplinary training.Read moreRead less