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
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
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
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
Boryl Pincers and Beyond: Taming Borometallic Chemistry. Industrial applications of coordination complexes in catalysis reduce energy input and environmental impact but almost exclusively involve classical donors such as nitrogen, oxygen, sulfur and phosphorus. Boron, whilst prevalent and environmentally benign, is under-utilised in such applications, in part due to the high reactivity of the metal boron bond.
This research will seek to tame and then exploit the unique features of boron within p ....Boryl Pincers and Beyond: Taming Borometallic Chemistry. Industrial applications of coordination complexes in catalysis reduce energy input and environmental impact but almost exclusively involve classical donors such as nitrogen, oxygen, sulfur and phosphorus. Boron, whilst prevalent and environmentally benign, is under-utilised in such applications, in part due to the high reactivity of the metal boron bond.
This research will seek to tame and then exploit the unique features of boron within pincer ligand frameworks in metal coordination complexes, with particular attention focusing on, but not limited to catalytic alkyne metathesis.Read moreRead less
Combating Antimicrobial Resistance with Bismuth, Gallium and Indium. This research project focuses on the design, development, and application of new bismuth, gallium and indium compounds as antimicrobial agents. These metals act as iron mimics in vivo and can exert antimicrobial activity while displaying low systemic toxicity in humans. The project aims to exploit this, and the inability of microbes to easily develop resistance towards metals, to combat bacteria for which modern drugs are rapid ....Combating Antimicrobial Resistance with Bismuth, Gallium and Indium. This research project focuses on the design, development, and application of new bismuth, gallium and indium compounds as antimicrobial agents. These metals act as iron mimics in vivo and can exert antimicrobial activity while displaying low systemic toxicity in humans. The project aims to exploit this, and the inability of microbes to easily develop resistance towards metals, to combat bacteria for which modern drugs are rapidly becoming ineffective, as highlighted in the WHO and US Centre for Disease Control list of critical and priority pathogens. The intended outcome is that efficacy will be driven through advances in synthetic and structural chemistry, discovering the mode of action, and creating anti-infective coatings and hydrogels.Read moreRead less
Antimicrobial and anti-Leishmanial bismuth compounds and materials. The project aims to develop the bioinorganic and medicinal chemistry of bismuth and related metals to address two global health issues: parasitic infections (principally Leishmaniasis) and antibacterial resistance. Through targeting serious microbial infections, the project will research the chemical, physical, structural and biological properties of bismuth and related metals. The project will form bio-protective materials and ....Antimicrobial and anti-Leishmanial bismuth compounds and materials. The project aims to develop the bioinorganic and medicinal chemistry of bismuth and related metals to address two global health issues: parasitic infections (principally Leishmaniasis) and antibacterial resistance. Through targeting serious microbial infections, the project will research the chemical, physical, structural and biological properties of bismuth and related metals. The project will form bio-protective materials and surfaces through incorporating bismuth and its compounds into polymer matrices. It will establish the complexes’ chemical biology and toxicology through scrutinising cellular mechanisms, particularly modern metallomic techniques. New compounds developed may address the urgent and significant health issue of antibiotic resistance and help address poorly treated parasitic infections.Read moreRead less
Dual-ion electrochemical systems. The project aims to develop dual-ion electrochemical systems. In contrast to conventional single-ion rechargeable cells, the charge storage process in the cathodes of these devices is facilitated by a second, negative ion. Dual-ion systems represent robust alternatives to current lithium-ion batteries and lithium-ion capacitors, addressing their sustainability and energy density limitations. The project’s outcomes are in the form of new sustainable energy storag ....Dual-ion electrochemical systems. The project aims to develop dual-ion electrochemical systems. In contrast to conventional single-ion rechargeable cells, the charge storage process in the cathodes of these devices is facilitated by a second, negative ion. Dual-ion systems represent robust alternatives to current lithium-ion batteries and lithium-ion capacitors, addressing their sustainability and energy density limitations. The project’s outcomes are in the form of new sustainable energy storage technologies with attrative energy and power densities for a wide range of applications. This should provide a significant benefit to society, the economy and the environment in enabling an easier transition to clean energy and ensuring energy security in Australia.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
Electrochemically activated solid state chemistry: A new synthetic avenue. This project aims to validate a new solid state synthetic route discovered in our group by understanding the reaction mechanism and experimenting with the parameter space of reaction variables. The discovery of a new solid state synthetic route opens up a world of possibility for the generation of new materials with a diverse range of potential functions and applications. The fundamental understanding of the reaction mech ....Electrochemically activated solid state chemistry: A new synthetic avenue. This project aims to validate a new solid state synthetic route discovered in our group by understanding the reaction mechanism and experimenting with the parameter space of reaction variables. The discovery of a new solid state synthetic route opens up a world of possibility for the generation of new materials with a diverse range of potential functions and applications. The fundamental understanding of the reaction mechanism will enable the rapid and widespread use of this synthetic route.Read moreRead less