Site-specific Conjugation of Zirconium and Copper Complexes to Antibodies for Application in Diagnostic Imaging and Therapy. This project will focus on fundamental chemistry that underpins innovations in the synthesis of metal-based imaging and therapeutic agents. Radioactive isotopes of copper and zirconium can be used for either non-invasive diagnostic imaging or treatment of disease. However, it is essential that the diagnostic or therapeutic agent selectively localises in diseased tissue. Th ....Site-specific Conjugation of Zirconium and Copper Complexes to Antibodies for Application in Diagnostic Imaging and Therapy. This project will focus on fundamental chemistry that underpins innovations in the synthesis of metal-based imaging and therapeutic agents. Radioactive isotopes of copper and zirconium can be used for either non-invasive diagnostic imaging or treatment of disease. However, it is essential that the diagnostic or therapeutic agent selectively localises in diseased tissue. This project aims to achieve the required selectivity by employing enzymatic site-specific bioconjugation reactions to build new imaging agents that feature ligands designed to safely bind radioactive isotopes fused to antibody derived targeting molecules.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.
Designing reactivity of homogeneous and heterogeneous water-splitting catalysts using muti-dimensional site-selective spectroscopies. New classes of heterogeneous manganese-calcium water splitting catalysts analogous to the unique biological water splitting cofactor have recently emerged but with far lower catalytic rates than seen for the biological system. These new materials are promising targets for large-scale hydrogen fuel production with low cost, high efficiency and ease of manufacture. ....Designing reactivity of homogeneous and heterogeneous water-splitting catalysts using muti-dimensional site-selective spectroscopies. New classes of heterogeneous manganese-calcium water splitting catalysts analogous to the unique biological water splitting cofactor have recently emerged but with far lower catalytic rates than seen for the biological system. These new materials are promising targets for large-scale hydrogen fuel production with low cost, high efficiency and ease of manufacture. To achieve this, the performance gap between these materials and the homogenous biological catalyst must be bridged. Multi-dimensional site-selective spectroscopies, including magneto/optical resonance methods which are aimed to be developed in this project are expected to provide new, atomic level understanding of properties needed to achieve high catalytic efficiency, thus guiding rational catalyst design.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
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
Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug ta ....Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug targets. This research will lead to new strategies in the design of improved anticancer drugs, which is an important Australian research priority that will promote and maintain good health, and provide potential commercial outcomes.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
Metals in biocatalysis. Metals and enzymes are essential for the chemistry of life. This project will aim to garner the potential of metal-dependent enzymes to develop new drugs against osteoporosis, combat the spread of antibiotics resistance and optimise some of these enzymes to detoxify pesticide-polluted environments, thus contributing to global health and food security.
Exploiting bacterial metal resistance machinery for metal ion nano-biosensors development. This project aims to integrate advanced materials chemistry, molecular biology, bio-electrochemical and synchrotron imaging approaches to understand the role of silver resistance machinery of bacteria in their ability to form silver nanoparticles. This aims to enable discovery of new metal-specific reductase enzymes. The fundamental biomolecular understanding of bacterial silver resistance will allow the u ....Exploiting bacterial metal resistance machinery for metal ion nano-biosensors development. This project aims to integrate advanced materials chemistry, molecular biology, bio-electrochemical and synchrotron imaging approaches to understand the role of silver resistance machinery of bacteria in their ability to form silver nanoparticles. This aims to enable discovery of new metal-specific reductase enzymes. The fundamental biomolecular understanding of bacterial silver resistance will allow the use of a silver-binding protein to develop a series of next-generation nano-biosensors. These biosensing platforms will provide high-throughput, cost-effective, selective, sensitive and continuous monitoring of heavy metal ions in effluents from mining and mineral processing industries in a real-time fashion.Read moreRead less
Building Advanced Materials from the Bottom Up. This proposal will result in new advanced materials with a range of useful properties, such as storage or trapping of gases such as hydrogen (for use in environmentally friendly transportation), methane and carbon dioxide (for pollution control), magnetic switching (with potential applications such as molecular sensors or data storage), new bulk and discrete nanometer sized magnets, and new liquids with novel solvent properties. These will be const ....Building Advanced Materials from the Bottom Up. This proposal will result in new advanced materials with a range of useful properties, such as storage or trapping of gases such as hydrogen (for use in environmentally friendly transportation), methane and carbon dioxide (for pollution control), magnetic switching (with potential applications such as molecular sensors or data storage), new bulk and discrete nanometer sized magnets, and new liquids with novel solvent properties. These will be constructed from carefully designed polymeric materials and unusual nanometer sized molecules. This proposal will also enable the applicant to develop and enhance overseas collaborations, particularly with a number of research groups in the emerging economy of China.Read moreRead less