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
Mycobacterial Cholesterol Degradation: A Unique Metabolic Weakness? This project aims to understand the use of the steroid cholesterol as a source of essential metabolic building blocks by bacteria. Cholesterol utilisation is a key feature of many bacterial pathogens which have evolved to survive in niche environments. By understanding the initial step in cholesterol degradation and the bioinorganic and bioorganic chemistry of the metalloenzymes that catalyse it, this work aims to develop strate ....Mycobacterial Cholesterol Degradation: A Unique Metabolic Weakness? This project aims to understand the use of the steroid cholesterol as a source of essential metabolic building blocks by bacteria. Cholesterol utilisation is a key feature of many bacterial pathogens which have evolved to survive in niche environments. By understanding the initial step in cholesterol degradation and the bioinorganic and bioorganic chemistry of the metalloenzymes that catalyse it, this work aims to develop strategies to block this activity. This will turn a key strength of these bacteria into a potent weakness and will generate the proof of principle and knowledge required for the future development of effective strategies to combat pathogenic bacteria.Read moreRead less
Deciphering Electron Transfer Pathways in Bacteria. Enzyme catalysed oxidation reactions are key players in the production of naturally occurring biologically active molecules. These processes are tightly regulated by their electron transfer partners. This project aims to characterise new electron transfer ferredoxin proteins from a metabolically diverse bacterium. These ferredoxins, important in many bacteria, contain different non-cysteine amino acids in their iron-sulfur cluster binding motif ....Deciphering Electron Transfer Pathways in Bacteria. Enzyme catalysed oxidation reactions are key players in the production of naturally occurring biologically active molecules. These processes are tightly regulated by their electron transfer partners. This project aims to characterise new electron transfer ferredoxin proteins from a metabolically diverse bacterium. These ferredoxins, important in many bacteria, contain different non-cysteine amino acids in their iron-sulfur cluster binding motifs and are poorly defined. The outcomes will advance understandings of electron transfer, a fundamental process. This will allow strategies to combat human and plant pathogens and unlock the potential of these systems as biocatalysts for the green chemical synthesis of complex and valuable chemicals.Read moreRead less
Pushing the Boundaries of Multi-modal Biospectroscopic Microscopies. In order to understand the fundamentals of life processes, diseases, and their treatments, it is essential to probe fundamental changes in molecular processes in cells, tissues and whole organisms. Much of our understanding of these processes has involved the introduction of chemical probes for biospectroscopy, but these have inherent problems because the probe can often change the biochemistry that is being probed. This projec ....Pushing the Boundaries of Multi-modal Biospectroscopic Microscopies. In order to understand the fundamentals of life processes, diseases, and their treatments, it is essential to probe fundamental changes in molecular processes in cells, tissues and whole organisms. Much of our understanding of these processes has involved the introduction of chemical probes for biospectroscopy, but these have inherent problems because the probe can often change the biochemistry that is being probed. This project will push the boundaries of a variety of micro and nano "probe-free" microscopies to provide fundamental insights into these life processes, which could ultimately lead to improvements in the diagnosis, prevention and treatment of diseases.Read moreRead less
The fate of dietary selenium in vivo; a direct approach to linking chemical form with biological activity. Dietary selenium supplementation has great potential as a preventative treatment for a range of human health conditions, including cancer, that widely affect the Australian population. However, the adverse effects of such treatments are not fully recognised. This project will increase our knowledge of how selenium compounds are stored and utilised in the body and relate the information to c ....The fate of dietary selenium in vivo; a direct approach to linking chemical form with biological activity. Dietary selenium supplementation has great potential as a preventative treatment for a range of human health conditions, including cancer, that widely affect the Australian population. However, the adverse effects of such treatments are not fully recognised. This project will increase our knowledge of how selenium compounds are stored and utilised in the body and relate the information to clinical observations regarding dietary intake of selenium and other compounds. The new understanding generated will delineate the conditions for safe intake, so that the beneficial effects associated with selenium supplementation may be harnessed more effectively.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100174
Funder
Australian Research Council
Funding Amount
$800,000.00
Summary
Innovative synchrotron science - program for access to the Australian National Beamline Facility and cutting-edge beamlines at international synchrotrons. Synchrotron science dramatically affects the community through the innovative scientific, engineering and medical research outcomes it produces. This program for access to synchrotron beamlines is aimed at enhancing Australia's high international standing in synchrotron science and will have many flow-on effects in areas such as health and ind ....Innovative synchrotron science - program for access to the Australian National Beamline Facility and cutting-edge beamlines at international synchrotrons. Synchrotron science dramatically affects the community through the innovative scientific, engineering and medical research outcomes it produces. This program for access to synchrotron beamlines is aimed at enhancing Australia's high international standing in synchrotron science and will have many flow-on effects in areas such as health and industry.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0346733
Funder
Australian Research Council
Funding Amount
$399,466.00
Summary
Ultra-Sensitive CCD Diffractometer with High Intensity X-ray Photon Generator. X-ray photon diffraction from single crystals provides the most accurate, precise and detailed three dimensional chemical structure information. It is however often difficult to obtain crystals of complex chemical assemblies, such as those used in nanotechnology and photon technology, suitable for diffraction analysis using equipment currently available at Australian chemical crystal structure facilities. The collab ....Ultra-Sensitive CCD Diffractometer with High Intensity X-ray Photon Generator. X-ray photon diffraction from single crystals provides the most accurate, precise and detailed three dimensional chemical structure information. It is however often difficult to obtain crystals of complex chemical assemblies, such as those used in nanotechnology and photon technology, suitable for diffraction analysis using equipment currently available at Australian chemical crystal structure facilities. The collaborating institutions seek to overcome this problem by purchasing a high sensitivity CCD area detector coupled to an intense laboratory source of X-ray photons. The installation of the equipment would be the first of its kind at an Australian facility and only the fourth worldwide.Read moreRead less
Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unch ....Gas Phase Reactivity of Charged Peptide and DNA Radicals: Fundamentals and Applications. Radicals derived from the "molecules of life", proteins and DNA, play both beneficial (e.g. enzyme catalysis) and deleterious roles (e.g. protein and DNA damage associated with disease). Two electrospray ionisation mass spectrometry approaches have been discovered to generate charged radicals of related models systems (e.g. peptides and nucleobases). The gas phase chemistry of these species is a largely unchartered area! We will examine the fundamental chemistry (unimolecular and bimolecular reactions) of these systems and build upon some exciting preliminary results which suggest potential applications (e.g. as a proteomics tool to sequence and distinguish between leucine and isoleucine residues in peptides).Read moreRead less
Development of a novel biodegradable ophthalmic biomaterial based on porous silicon. Within this interdisciplinary project, we will combine our diverse expertise towards the development of frontier technologies for control of stem cell behaviour on biodegradable scaffold materials. We will develop a novel ophthalmic bioimplant from porous silicon using topographical and chemical aspects of surface modification as well as immobilisation and/or incorporation of bioactive species such as growth fac ....Development of a novel biodegradable ophthalmic biomaterial based on porous silicon. Within this interdisciplinary project, we will combine our diverse expertise towards the development of frontier technologies for control of stem cell behaviour on biodegradable scaffold materials. We will develop a novel ophthalmic bioimplant from porous silicon using topographical and chemical aspects of surface modification as well as immobilisation and/or incorporation of bioactive species such as growth factors, to permit the growth and differentiation of mammalian stem cells. This project will result in biomaterials for the treatment of blinding diseases of the eye. Implanted into the limbus, bioimplants may ameliorate some common corneal diseases.Read moreRead less