Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations ....Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations of super resolution microscopy to visualise in 3 dimensions how changes in chromatin modifications impact genome spatial organisation within the nucleus, and how this then links to cellular differentiation. This will provide a picture of how spatial organisation within the nucleus supports general cell differentiation.
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Discovery Early Career Researcher Award - Grant ID: DE240100992
Funder
Australian Research Council
Funding Amount
$448,237.00
Summary
New methods to capture protein dynamics of the TSC-mTOR signalling axis. Protein flexibility, the way proteins move, has a major role in how they function. However, we still do not have the tools to analyse this flexibility. Our cells have evolved many complex and flexible systems to sense and respond to their environment. For example, the TSC-mTOR system is found across life, from baker’s yeast to humans, however it remains poorly understood. This proposal will study TSC as an exemplar to devel ....New methods to capture protein dynamics of the TSC-mTOR signalling axis. Protein flexibility, the way proteins move, has a major role in how they function. However, we still do not have the tools to analyse this flexibility. Our cells have evolved many complex and flexible systems to sense and respond to their environment. For example, the TSC-mTOR system is found across life, from baker’s yeast to humans, however it remains poorly understood. This proposal will study TSC as an exemplar to develop novel machine-learning approaches to capture protein flexibility and shape. This proposal will advance fundamental understanding of the TSC-mTOR pathway and build transformative methodologies to study flexible proteins more broadly.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
3D integrated crystalline UV optical lens-fiber couplers for astronomy. This project aims to create micro-optics for astronomical and bio medical applications by 3D sculpturing them out of crystals by ultra-short pulse lasers. This project will introduce a new 3D fabrication approach of optical probes which have self-aligned micro-optical elements and optical fibres for a wide spectral range and with high quality optical surfaces. Expected outcomes of this project include building new capabiliti ....3D integrated crystalline UV optical lens-fiber couplers for astronomy. This project aims to create micro-optics for astronomical and bio medical applications by 3D sculpturing them out of crystals by ultra-short pulse lasers. This project will introduce a new 3D fabrication approach of optical probes which have self-aligned micro-optical elements and optical fibres for a wide spectral range and with high quality optical surfaces. Expected outcomes of this project include building new capabilities in micro-optical probes for industrial environments, establishing new solutions for international astronomy partners, and developing new techniques to image through optical fibres. This should provide significant benefits by improving astronomical instrumentation and also lead to less invasive endoscopy.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240101035
Funder
Australian Research Council
Funding Amount
$450,760.00
Summary
Charting the brain's wiring over the human lifespan. This project aims to produce a large-scale model of brain wiring over the human lifespan by utilising normative modelling approaches on state-of-the-art diffusion magnetic resonance imaging (diffusion MRI) data. This project expects to generate new understanding of how the brain's connections change with age in healthy individuals. Expected outcomes of this project include a reference chart for healthy brain wiring, and major advances in diffu ....Charting the brain's wiring over the human lifespan. This project aims to produce a large-scale model of brain wiring over the human lifespan by utilising normative modelling approaches on state-of-the-art diffusion magnetic resonance imaging (diffusion MRI) data. This project expects to generate new understanding of how the brain's connections change with age in healthy individuals. Expected outcomes of this project include a reference chart for healthy brain wiring, and major advances in diffusion MRI data harmonisation approaches. This should provide significant benefits for the translation of advanced diffusion MRI methods, as normative charts for brain wiring will be made broadly available. This could have broad implications for interpreting individual diffusion MRI scans in future.Read moreRead less
Next Generation Fluorescent Tools for Measuring Autophagy Dynamics in Cells. This project aims to create new molecular tools for detecting a crucial cell survival process called autophagy. Specifically, this project will develop small molecule fluorescent probes that are specific to autophagy, for the first time, by interacting with the key autophagy marker proteins or cargos. This will allow researchers to visualise and quantify autophagy activity in living cells without disrupting the system, ....Next Generation Fluorescent Tools for Measuring Autophagy Dynamics in Cells. This project aims to create new molecular tools for detecting a crucial cell survival process called autophagy. Specifically, this project will develop small molecule fluorescent probes that are specific to autophagy, for the first time, by interacting with the key autophagy marker proteins or cargos. This will allow researchers to visualise and quantify autophagy activity in living cells without disrupting the system, which is not currently possible. This project represents a major technical and knowledge advance that will improve our understanding of autophagy in fundamental biology and ultimately contribute to the development of new intervention strategies for diseases like neurodegeneration and cancers.Read moreRead less
Precise atomic-scale structure determination in thick nanostructures. This project aims to tackle a great challenge of atomic-scale characterisation: quantitative structure determination. Powerful new electron microscopes offer a window into the atomic world, but complex electron multiple scattering has limited reliable structure determination to ultrathin materials. This project expects to overcome this barrier. Anticipated outcomes include methods that use the latest detector technology to det ....Precise atomic-scale structure determination in thick nanostructures. This project aims to tackle a great challenge of atomic-scale characterisation: quantitative structure determination. Powerful new electron microscopes offer a window into the atomic world, but complex electron multiple scattering has limited reliable structure determination to ultrathin materials. This project expects to overcome this barrier. Anticipated outcomes include methods that use the latest detector technology to determine structure and interatomic bonding in much thicker nanostructures than hitherto possible. This should benefit academic and industrial researchers by giving them new tools to understand and design high-performance materials for applications ranging from catalysis to energy storage to next-generation electronics.Read moreRead less
Atomic scale ion microscopy via laser cooling and correlated imaging. This project will develop next-generation focused ion beam microscopy and nanofabrication using a novel cold ion source based on photoionisation of a laser-cooled atom beam. The low temperature and complex internal state structure of the constituent atoms combine to allow generation of ions with unprecedented brightness and resolution. We will use three unique and innovative ideas: field ionisation of atoms in so-called 'excep ....Atomic scale ion microscopy via laser cooling and correlated imaging. This project will develop next-generation focused ion beam microscopy and nanofabrication using a novel cold ion source based on photoionisation of a laser-cooled atom beam. The low temperature and complex internal state structure of the constituent atoms combine to allow generation of ions with unprecedented brightness and resolution. We will use three unique and innovative ideas: field ionisation of atoms in so-called 'exceptional' states to reduce chromatic aberration; electron-ion correlations to enhance control of the ions at the nanoscale; and atom-atom interactions to isolate and manipulate individual ions. The new technology will enable advances in semiconductor nanofabrication and material characterisation.Read moreRead less