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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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
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
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
How the red blood cell loses its nucleus. This project aims to provide insights into erythroid enucleation, the process by which red blood cells extrude their nucleus so that they can circulate through the microvasculature. Although the enucleated character of mammalian red blood cells has been known for more than 150 years, the mechanism underlying this process is virtually unknown. This project will use a live imaging approach to characterise in vivo the cellular interactions and molecular pat ....How the red blood cell loses its nucleus. This project aims to provide insights into erythroid enucleation, the process by which red blood cells extrude their nucleus so that they can circulate through the microvasculature. Although the enucleated character of mammalian red blood cells has been known for more than 150 years, the mechanism underlying this process is virtually unknown. This project will use a live imaging approach to characterise in vivo the cellular interactions and molecular pathways required for enucleation. The project will provide a molecular and cellular road map of enucleation that may be utilised to enhance the bulk therapeutic in vitro production of red blood cells for veterinary and human purposes.Read moreRead less
Tissue Bio-physicochemical Quantification Using Magnetic Resonance Imaging. This project aims to develop novel magnetic resonance imaging methods to investigate tissue structure and function. Current MRI technologies use standard water-based contrast mechanisms to generate images with limited tissue information. In contrast, this project expects to provide a non-invasive, ultra-high-resolution MRI technology that measures the electrical, magnetic, and chemical signals generated from the human bo ....Tissue Bio-physicochemical Quantification Using Magnetic Resonance Imaging. This project aims to develop novel magnetic resonance imaging methods to investigate tissue structure and function. Current MRI technologies use standard water-based contrast mechanisms to generate images with limited tissue information. In contrast, this project expects to provide a non-invasive, ultra-high-resolution MRI technology that measures the electrical, magnetic, and chemical signals generated from the human body. Thus, the new imaging methods can probe deeper biological functionality while examining tissue structure. The potential benefits include: expanding the scope and capabilities of current MRI, facilitating a wide range of imaging-based research and applications, and accelerating knowledge expansion in life science.Read moreRead less
X-ray Ghost Imaging and Tomography. This project aims to achieve safer, faster, and cheaper 3D X-ray imaging through a technique known as ghost imaging. X-ray imaging provides valuable information about internal structures, however, X-rays are carcinogenic and exposure (or dose) should be limited. Ghost imaging is an unconventional technique developed with visible light that has many potential benefits over conventional imaging. This research group are world leaders in ghost imaging and expect t ....X-ray Ghost Imaging and Tomography. This project aims to achieve safer, faster, and cheaper 3D X-ray imaging through a technique known as ghost imaging. X-ray imaging provides valuable information about internal structures, however, X-rays are carcinogenic and exposure (or dose) should be limited. Ghost imaging is an unconventional technique developed with visible light that has many potential benefits over conventional imaging. This research group are world leaders in ghost imaging and expect to develop software and hardware techniques to realise its potential and extend it to ghost tomography. The focus of this project is on reducing cancer risk in medical imaging, and allowing real-time quality control for 3D printing in safety-critical industries such as aerospace.Read moreRead less
Imaging Symmetry – A New Mechanism for Revealing the Structure of Matter. This project aims to develop a revolutionary method for imaging atomic structures. In this method, the image contrast derives from the symmetry of the structure, measured at the picometre scale, using tiny electron probes. This new conceptual approach is expected to overcome some of the key limitations of existing electron microscopy methods by providing increased sensitivity and reduced radiation damage, thereby enabling ....Imaging Symmetry – A New Mechanism for Revealing the Structure of Matter. This project aims to develop a revolutionary method for imaging atomic structures. In this method, the image contrast derives from the symmetry of the structure, measured at the picometre scale, using tiny electron probes. This new conceptual approach is expected to overcome some of the key limitations of existing electron microscopy methods by providing increased sensitivity and reduced radiation damage, thereby enabling complex structures in technologically important materials to be determined. This should provide new ways to understand the properties of these materials advanced materials and engineer them for applications in the energy, transport, health, communications and other sectors of society. Read moreRead less
Visualising Retinal Microglia as a Window into Brain Inflammation. This project aims to use the unique autofluorescence signature of immune cells, microglia, imaged in the retina, as an index of brain inflammation. This project expects to provide the fundamental knowledge to allow us to image microglia non-invasively and identify the presence of brain inflammation without needing to access the brain-proper. Expected outcomes include full characterisation of microglial autofluorescence in the ret ....Visualising Retinal Microglia as a Window into Brain Inflammation. This project aims to use the unique autofluorescence signature of immune cells, microglia, imaged in the retina, as an index of brain inflammation. This project expects to provide the fundamental knowledge to allow us to image microglia non-invasively and identify the presence of brain inflammation without needing to access the brain-proper. Expected outcomes include full characterisation of microglial autofluorescence in the retina and how it relates to brain inflammation. This should provide significant downstream benefits for the detection of inflammatory brain disease well before visible symptoms develop with substantial benefit for livestock, pets, zoo and conservation animals, as well as research knowledge. Read moreRead less