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
Enhancing our understanding of metallochemistry in neurobiology with modern electron paramagnetic resonance (EPR) spectroscopy. Many neurological diseases involve protein accumulation that appears causally linked to abnormal levels of metal ions in the brain. This project will use a special technique called electron paramagnetic resonance to uncover how these metals interact with specific proteins at the molecular level and how drug treatments can modify these interactions.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100061
Funder
Australian Research Council
Funding Amount
$710,000.00
Summary
Extending frontiers of structural chemistry and biology through high resolution pulsed Electron Paramagnetic Resonance. Multifrequency high resolution pulsed Electron Paramagnetic Resonance (EPR) instrumentation will provide forefront technologies in identifying, characterising, quantifying and visualising free radicals and metal ions that are involved in fundamental chemical and biological processes in science and nature.
Understanding how cells store and use iron . This project aims to understand the mechanism and function of the protein nanocage, ferritin, which stores iron in the body ready for use on demand. Iron is an essential element, vital for wellbeing. To understand iron we need to understand ferritin. Despite being widely studied, how ferritin actually works remains unclear. This project aims to use an interdisciplinary approach combining protein biochemistry, spectroscopy, genetics and whole organism ....Understanding how cells store and use iron . This project aims to understand the mechanism and function of the protein nanocage, ferritin, which stores iron in the body ready for use on demand. Iron is an essential element, vital for wellbeing. To understand iron we need to understand ferritin. Despite being widely studied, how ferritin actually works remains unclear. This project aims to use an interdisciplinary approach combining protein biochemistry, spectroscopy, genetics and whole organism studies. It will develop new techniques to enable the physiological role of iron to be explored. Outcomes of this innovative platform are anticipated to include in-depth understanding of how ferritin functions to unravel its fundamental role in iron storage and release ready for re-use.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
Accessing the therapeutic potential of carbon monoxide. Despite carbon monoxide being regarded as the ”silent killer”, it is now established that this molecule has beneficial effects for a number of conditions and pathologies, including inflammation, organ transplant rejection, bacterial infection, acute liver failure and as an aid in cancer therapies. This project proposes to explore the photochemistry of rhenium-containing species to discover more efficient carbon monoxide delivery agents. By ....Accessing the therapeutic potential of carbon monoxide. Despite carbon monoxide being regarded as the ”silent killer”, it is now established that this molecule has beneficial effects for a number of conditions and pathologies, including inflammation, organ transplant rejection, bacterial infection, acute liver failure and as an aid in cancer therapies. This project proposes to explore the photochemistry of rhenium-containing species to discover more efficient carbon monoxide delivery agents. By combining synthetic chemistry, photochemistry and cellular biology it is anticipated that this multidisciplinary research programme will advance the area of carbon monoxide therapies by preparing safer agents for the targeted and controlled delivery of carbon monoxide.Read moreRead less
Bioinorganic chemistry between immune cell and pathogen. This project aims to investigate the bioinorganic chemistry that occurs when immune system cells encounter pathogens and they try to kill one another, or in the case of a pathogen, to also modify the genetics of the mammalian cell to enable its intracellular survival. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes and it was recently discovered that Cr is likely to be an important virulence factor. Similarly, H ....Bioinorganic chemistry between immune cell and pathogen. This project aims to investigate the bioinorganic chemistry that occurs when immune system cells encounter pathogens and they try to kill one another, or in the case of a pathogen, to also modify the genetics of the mammalian cell to enable its intracellular survival. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes and it was recently discovered that Cr is likely to be an important virulence factor. Similarly, Hyperaccummulation of Nickel (Ni) is also involved in virulence. The project will investigate the roles of Cr and Ni in virulence using advanced spectroscopic imaging and biochemical techniques. These insights will provide new knowledge on the innate immune system and may lead to more efficacious treatments for serious infections.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
NMR Studies of Second Generation Polynuclear Platinum Compounds. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration between Prof. Berners-Price and the inventor of these ne ....NMR Studies of Second Generation Polynuclear Platinum Compounds. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration between Prof. Berners-Price and the inventor of these new drugs puts Australian research at the forefront of the clinical development. There is the potential for the generation of new IP from new strategies in the design of improved anticancer drugs. The project builds strong international links and provides international training for Australian PhD students.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