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
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
Redox sulphur chemistry in copper nutrition. Problems with metabolism of the nutrient metal copper are associated with many diseases including tuberculosis, heart disease and Alzheimer's disease. The project will examine the role of copper in unprecedented molecular detail to better understand its influence on normal metabolism and hence its impact on the diseases.
How does redox cycling drive the metabolism of the essential metals iron and copper? Iron and copper are essential metal nutrients but mishandling leads to cardiovascular, metabolic and neurological disease. Intriguingly, some enzymes handle both iron and copper and this project will develop new methods for their study. The work will lead ultimately to enlightened prevention and effective management of the multiple diseases.
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
Molecular study of copper-promoted ubiquitination. This project aims to study copper-promoted ubiquitination, a novel discovery that a conserved copper binding site in conjugating enzyme UBE2D2 promotes ubiquitination of a range of proteins including tumor suppressor p53. It predicts a correlation between copper homeostasis and cellular proteostasis and may rationalise an inverse relationship between Alzheimer's disease and cancer. This project will employ a range of integrated approaches to ill ....Molecular study of copper-promoted ubiquitination. This project aims to study copper-promoted ubiquitination, a novel discovery that a conserved copper binding site in conjugating enzyme UBE2D2 promotes ubiquitination of a range of proteins including tumor suppressor p53. It predicts a correlation between copper homeostasis and cellular proteostasis and may rationalise an inverse relationship between Alzheimer's disease and cancer. This project will employ a range of integrated approaches to illuminate the molecular nature of this copper action. Expected outcomes include an understanding of the molecular mechanisms of this process, and enhanced interdisciplinary collaboration. Potential benefits include new strategies to intervene in copper-related disorders.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
Gallium, Copper and Metal Fluoride Complexes Designed for Brain Imaging. This project aims to develop fundamental synthetic coordination chemistry directed toward the development of new agents for imaging brain perfusion using positron emission tomography. The research will focus on developing new coordination complexes containing positron-emitting isotopes of copper, gallium and fluorine. The goal is incorporate in these radionuclides into small molecules that can be used for the molecular imag ....Gallium, Copper and Metal Fluoride Complexes Designed for Brain Imaging. This project aims to develop fundamental synthetic coordination chemistry directed toward the development of new agents for imaging brain perfusion using positron emission tomography. The research will focus on developing new coordination complexes containing positron-emitting isotopes of copper, gallium and fluorine. The goal is incorporate in these radionuclides into small molecules that can be used for the molecular imaging of the brain. This chemistry will have the potential to replace existing technologies that rely on single-photon emission from technetium and the technique of single photon emission computed tomography.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210101168
Funder
Australian Research Council
Funding Amount
$430,000.00
Summary
Shining a light on the mechanism of photochemical hydrogen production. This project aims to improve the performance and longevity of molecular photocatalysts to produce hydrogen from water and visible light. Sustainable alternatives to fossils fuels, such as hydrogen, are critical to minimising the effects of climate change. This project expects to use innovative experimental techniques to reveal the causes of degradation in key intermediates of the photocatalytic reaction. Understanding these d ....Shining a light on the mechanism of photochemical hydrogen production. This project aims to improve the performance and longevity of molecular photocatalysts to produce hydrogen from water and visible light. Sustainable alternatives to fossils fuels, such as hydrogen, are critical to minimising the effects of climate change. This project expects to use innovative experimental techniques to reveal the causes of degradation in key intermediates of the photocatalytic reaction. Understanding these detrimental pathways can then direct the design of new catalysts with enhanced stability and activity. The fundamental chemistry explored in this project should advance breakthroughs in artificial photosynthesis and provide cleaner methods of hydrogen production under mild conditions, using earth-abundant catalysts.Read moreRead less