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
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
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
Discovering New Chemistry and Potential Applications of Metal Tetrapyrroles. This project aims to make fundamental advances in inorganic chemistry, coordination chemistry and bioinorganic chemistry by preparing new metal-containing molecules based on specifically designed tetrapyrrole ligands. Innovative synthetic methods will be developed to enable systematic chemical modifications to explore the chemical and biological properties of the metal complexes. The potential of the new molecules to be ....Discovering New Chemistry and Potential Applications of Metal Tetrapyrroles. This project aims to make fundamental advances in inorganic chemistry, coordination chemistry and bioinorganic chemistry by preparing new metal-containing molecules based on specifically designed tetrapyrrole ligands. Innovative synthetic methods will be developed to enable systematic chemical modifications to explore the chemical and biological properties of the metal complexes. The potential of the new molecules to be of use as tracers for molecular imaging will be investigated. An expected outcome of this research will be an increased understanding of how chemical properties dictate the biological activity of metal complexes informing the potential long-term translation of this chemistry to to new molecular diagnostics and therapeutics.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210101176
Funder
Australian Research Council
Funding Amount
$445,000.00
Summary
Fluorescent probes for super-resolution imaging of the amyloid architecture. The goal of this project is to develop chemical tools that enable molecular-level imaging of the amyloid structure. The Nobel Prize-winning super-resolution microscopy provides nanoscale imaging capabilities, but surprisingly there have been no substantive efforts to design fluorescent sensors that are compatible with this cutting-edge technology. In this project, new fluorescent super-resolution sensors will be develop ....Fluorescent probes for super-resolution imaging of the amyloid architecture. The goal of this project is to develop chemical tools that enable molecular-level imaging of the amyloid structure. The Nobel Prize-winning super-resolution microscopy provides nanoscale imaging capabilities, but surprisingly there have been no substantive efforts to design fluorescent sensors that are compatible with this cutting-edge technology. In this project, new fluorescent super-resolution sensors will be developed that enable nanoscale visualisation of amyloid assemblies. These chemical and biochemical studies will establish rational design strategies to develop fluorescent sensors for super-resolution imaging applications and significantly advance our understanding of fundamental differences functional and toxic protein assemblies.Read moreRead less
Mechanisms maintaining mitochondrial copper homeostasis. This project aims to define the molecular mechanisms by which copper is trafficked and balanced within mitochondria. The project will employ an integrated biological, biochemical, biophysical and structural approach to examine the proteins which underpin the balance between the essentiality for copper and its toxicity, within this organelle. This project will deliver fundamental insights into how mitochondria contribute to and achieve cell ....Mechanisms maintaining mitochondrial copper homeostasis. This project aims to define the molecular mechanisms by which copper is trafficked and balanced within mitochondria. The project will employ an integrated biological, biochemical, biophysical and structural approach to examine the proteins which underpin the balance between the essentiality for copper and its toxicity, within this organelle. This project will deliver fundamental insights into how mitochondria contribute to and achieve cellular metal homeostasis, in addition to molecular explanations for how faults in this process result in mitochondrial defects. Major benefits include research training, strengthened international linkages and fundamental insights into mitochondrial biochemistry.Read moreRead less
Metal Virulence and Therapeutic Factors in Pathogen Bioinorganic Chemistry. The aim is to gain insights into the bioinorganic chemistry that occurs when immune system cells encounter pathogens and the soles of virulence factors and immune system enhancing roles of metal ions. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes/outer capsules, which we discovered is likely to be a previously unknown, but important, virulence factor. Hyperaccummulation of nickel (Ni) is also ....Metal Virulence and Therapeutic Factors in Pathogen Bioinorganic Chemistry. The aim is to gain insights into the bioinorganic chemistry that occurs when immune system cells encounter pathogens and the soles of virulence factors and immune system enhancing roles of metal ions. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes/outer capsules, which we discovered is likely to be a previously unknown, but important, virulence factor. Hyperaccummulation of nickel (Ni) is also involved in virulence, whereas vanadium (V) enhances the immune system response to these pathogens. Fundamental insights into these roles of Cr, Ni and V will be investigated using advanced spectroscopic, imaging and biochemical techniques. These insights will provide new knowledge on the innate immune system.Read moreRead less
Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected ....Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected to help guide the development of new agents for selectively delivering imaging and biologically active agents to cells.Read moreRead less
Enzyme-Mediated Machining of Chelators to Bind and Recover Valuable Metals. Metals are critical components of electronic devices and electrical products. Rapid disposal cycles create a major problem in managing e-waste metals and identifies an opportunity in the circular economy for recovery and re-use. Organic compounds that bind metal ions (chelators) are useful but could be improved to select a target metal from a mixture. This project aims to dissect a method used by bacteria to biosynthesiz ....Enzyme-Mediated Machining of Chelators to Bind and Recover Valuable Metals. Metals are critical components of electronic devices and electrical products. Rapid disposal cycles create a major problem in managing e-waste metals and identifies an opportunity in the circular economy for recovery and re-use. Organic compounds that bind metal ions (chelators) are useful but could be improved to select a target metal from a mixture. This project aims to dissect a method used by bacteria to biosynthesize chelators and hijack this to bioengineer new classes of chelators. Outcomes include new chelators and advanced knowledge of metal selectivity, with potential environmental and economic benefits arising from recovery of valuable metals. The project will benefit chemical biology research training for real-world applications.Read moreRead less