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Visualising molecular level detail in single cells and intact tissues. The goal of this project is to deliver a new toolkit for imaging cells at an unprecedented resolution and level of chemical detail. We will expand the capabilities of two existing, but complementary, methods: optical fluorescence microscopy with responsive probes and X-ray fluorescence imaging. Expected outcomes include improved techniques and benchmarks for visualising bacterial and mammalian cells; development of new molecu ....Visualising molecular level detail in single cells and intact tissues. The goal of this project is to deliver a new toolkit for imaging cells at an unprecedented resolution and level of chemical detail. We will expand the capabilities of two existing, but complementary, methods: optical fluorescence microscopy with responsive probes and X-ray fluorescence imaging. Expected outcomes include improved techniques and benchmarks for visualising bacterial and mammalian cells; development of new molecules for elucidating cellular chemistry; better utilisation of valuable synchrotron resources; and greater understanding of the strengths and limitations of current microscopy workflows. Results should benefit the biotechnology sector, and may lead to improved medical, diagnostic, and bioremediation capacity.Read moreRead less
Profiling tissue protein, elemental ions and nanoparticle distributions. This project aims to investigate protein-protein interactions that are crucial to homeostatic cell signalling and viability in a changing tissue environment. The central goal is to develop and validate protocols to combine cutting-edge tissue imaging modalities to map and characterise tissue distributions of native and modified proteins, elemental ions and pharmacological agents including nanoparticles and nanovehicles. The ....Profiling tissue protein, elemental ions and nanoparticle distributions. This project aims to investigate protein-protein interactions that are crucial to homeostatic cell signalling and viability in a changing tissue environment. The central goal is to develop and validate protocols to combine cutting-edge tissue imaging modalities to map and characterise tissue distributions of native and modified proteins, elemental ions and pharmacological agents including nanoparticles and nanovehicles. The aim is to use novel tissue scanning mass spectrometry techniques in conjunction with X-ray-based microprobe spectroscopy and advanced multi-parameter cytometry to identify spatial distributions of proteins, ions and drugs in tissues. This approach may provide new information about the maintenance of homeostatic control and the content, distribution and potential metabolism of drugs or nanoparticles within biological tissues.Read moreRead less
Characterisation of the beneficial vs toxic forms of selenium in the diet. This project aims to examine how dietary selenium is converted into essential proteins and beneficial compounds that mitigate against a broad range of human diseases; or alternatively, into toxic molecules. Cutting-edge methodologies should resolve significant unknowns in selenium metabolism, to provide definitive dietary guidelines and to explore how selenium can treat and protect against disease. Expected outcomes from ....Characterisation of the beneficial vs toxic forms of selenium in the diet. This project aims to examine how dietary selenium is converted into essential proteins and beneficial compounds that mitigate against a broad range of human diseases; or alternatively, into toxic molecules. Cutting-edge methodologies should resolve significant unknowns in selenium metabolism, to provide definitive dietary guidelines and to explore how selenium can treat and protect against disease. Expected outcomes from this national and international collaboration include expert training for young biochemical researchers and refinements to novel analytical techniques. Results should benefit the food and agricultural sectors to provide tailored products locally and for export, as well as enhanced health opportunities for all Australians.Read moreRead less
Probing nanoscale disorder in 3D with x-ray free-electron lasers. This project aims to reveal the 3D nanostructure of disordered matter with x-rays for the first time. Existing x-ray scattering techniques for disordered structures currently provide limited, one-dimensional information only. The expected outcomes of the project include an enhanced new capability for the Australian Synchrotron and international x-ray laser facilities, and new insights into the microscopic origins of the properties ....Probing nanoscale disorder in 3D with x-ray free-electron lasers. This project aims to reveal the 3D nanostructure of disordered matter with x-rays for the first time. Existing x-ray scattering techniques for disordered structures currently provide limited, one-dimensional information only. The expected outcomes of the project include an enhanced new capability for the Australian Synchrotron and international x-ray laser facilities, and new insights into the microscopic origins of the properties of liquids and biological membranes. This should benefit research areas that use x-ray scattering to probe the nanostructure of materials for diverse applications such as nanotechnology, fuel cells and drug design.Read moreRead less
Imaging metal homeostasis in the ageing brain. This fellowship aims to deliver new tools to visualise how changes to blood vessels during ageing effect the amount and distribution of metal ions in brain cells in animal models. This will be a significant advance as current methods cannot image these parameters. Metal ions are essential for brain function, but the effects of ageing on metal ions within brain cells is largely unknown. The results are expected to associate brain-blood vessel permeab ....Imaging metal homeostasis in the ageing brain. This fellowship aims to deliver new tools to visualise how changes to blood vessels during ageing effect the amount and distribution of metal ions in brain cells in animal models. This will be a significant advance as current methods cannot image these parameters. Metal ions are essential for brain function, but the effects of ageing on metal ions within brain cells is largely unknown. The results are expected to associate brain-blood vessel permeability with changes to metal ion content during ageing. The methods developed, and the fundamental new knowledge they reveal will benefit national and international neuroscientists seeking to elucidate the fundamental neurobiology of metal ions with respect to maintaining healthy brain function.Read moreRead less
Nanoimaging the cellular architecture of the malaria parasite, Plasmodium falciparum. The immediate benefit of this work will be in the understanding and treatment of malaria - a disease that kills approximately 1 million children annually. The ability to image the three-dimensional structure of cells at high resolution will allow us to ask fundamental questions about the cellular architecture of the malaria parasite and to design novel antimalarial strategies. By developing new methods for cor ....Nanoimaging the cellular architecture of the malaria parasite, Plasmodium falciparum. The immediate benefit of this work will be in the understanding and treatment of malaria - a disease that kills approximately 1 million children annually. The ability to image the three-dimensional structure of cells at high resolution will allow us to ask fundamental questions about the cellular architecture of the malaria parasite and to design novel antimalarial strategies. By developing new methods for correlating structure and elemental location, the work in this proposal will offer a new paradigm for the study of cellular function and disease. This represents an important advance in the suite of investigative tools available to the biotechology sector and will see a corresponding improvement in our understanding of a wide range of disease states.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120101504
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Nano-resolution hard x-ray diffraction imaging with conventional laboratory sources. The project will combine advanced optics and algorithms for diffraction imaging to develop a desktop hard x-ray microscope. The system will display ultra-high resolution and will be highly complementary to electronic and optical microscopies for diverse applications in materials engineering, nanofluidics and cell biology.
Extending X-ray Crystallography to Allow Structure Retrieval from Highly Disordered Crystals and Nanocrystals. X-ray crystallography is one of the most important tools in structural biology, responsible for over 80 per cent of the protein structures solved today. Obtaining X-ray diffraction data however is critically dependent on having large, high quality crystals. Many proteins, particularly membrane proteins, only form nanocrystals or crystals of poor quality which prevents their structure be ....Extending X-ray Crystallography to Allow Structure Retrieval from Highly Disordered Crystals and Nanocrystals. X-ray crystallography is one of the most important tools in structural biology, responsible for over 80 per cent of the protein structures solved today. Obtaining X-ray diffraction data however is critically dependent on having large, high quality crystals. Many proteins, particularly membrane proteins, only form nanocrystals or crystals of poor quality which prevents their structure being solved. This project aims to combine ideas from X-ray coherent diffraction imaging and X-ray crystallography to develop a method that can be used for structure retrieval from nanocrystals or crystals which are highly disordered. A particular emphasis will be placed on solving the structure of membrane proteins which are of special importance in drug development.Read moreRead less