Expanding access to modified proteins via a novel semi-synthetic platform. This project aims to address a critical knowledge gap in understanding how post-translational modifications modulate the structure and activity of proteins. By developing an innovative semi-synthetic platform to produce pure proteins inaccessible by existing methods, the project will reveal how natural protein modifications influence structure and function. Expected outcomes include the delivery of breakthrough technologi ....Expanding access to modified proteins via a novel semi-synthetic platform. This project aims to address a critical knowledge gap in understanding how post-translational modifications modulate the structure and activity of proteins. By developing an innovative semi-synthetic platform to produce pure proteins inaccessible by existing methods, the project will reveal how natural protein modifications influence structure and function. Expected outcomes include the delivery of breakthrough technologies for accessing modified proteins for a range of applications in academia and industry, as well as the generation of new knowledge in the fields of chemistry and biology. The project will lead to the training of interdisciplinary early career researchers and has the potential to benefit Australia’s biotechnology sector.Read moreRead less
Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes i ....Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes it can be applied to and the mechanisms underlying this technology. The outcomes of this project will facilitate the future development of peptides for biotechnology, pharmaceutical and veterinary applications.Read moreRead less
Dinuclear Ruthenium Complexes as Sequence- and Structure-Selective Binding Agents for DNA. Studies of the interaction of mononuclear metal complexes with DNA have greatly increased our understanding of the ways that small molecules recognise particular sites on DNA. However, in order to design drugs that target specific genes, and hence be potentially capable of controlling gene expression, it is necessary to study the binding of metal complexes that can associate with larger segments of DNA. ....Dinuclear Ruthenium Complexes as Sequence- and Structure-Selective Binding Agents for DNA. Studies of the interaction of mononuclear metal complexes with DNA have greatly increased our understanding of the ways that small molecules recognise particular sites on DNA. However, in order to design drugs that target specific genes, and hence be potentially capable of controlling gene expression, it is necessary to study the binding of metal complexes that can associate with larger segments of DNA. Using the combined expertise of the applicants, it is proposed to stereospecifically synthesise dinuclear complexes and study their DNA binding. This will greatly assist in the development of drugs that can selectively target genes and altered DNA.Read moreRead less
A peptide platform to fight pests threatening global food security. This project aims to develop a platform technology for the efficient design of new crop protection agents based on peptides to protect Australia’s food security. It will be first applied against the highly destructive fall armyworm, currently spreading alarmingly in Australia. The project is significant because insect pests cause huge economic and environmental impacts. Peptides are a new generation of crop protection agents tha ....A peptide platform to fight pests threatening global food security. This project aims to develop a platform technology for the efficient design of new crop protection agents based on peptides to protect Australia’s food security. It will be first applied against the highly destructive fall armyworm, currently spreading alarmingly in Australia. The project is significant because insect pests cause huge economic and environmental impacts. Peptides are a new generation of crop protection agents that are potentially more effective and sustainable than chemical pesticides. Expected outcomes are a new rapid response technology and associated lead molecules to protect against current and emerging pests. Major benefits are increased food security, improved crop yields and a more sustainable agriculture industry. Read moreRead less
Reactions of Nanoparticles of Metal Oxides and Hydrous Oxides and their Applications in Photocatalysts and Electrode Materials. Australia is a world-leading producer of raw materials of many metallic elements, most of which are exported at low-values. This project will yield important knowledge in new synthetic techniques for making nanostructures of metal oxides. These tiny particles already have a large worldwide market, but the discovery of particles with superior properties or new applicatio ....Reactions of Nanoparticles of Metal Oxides and Hydrous Oxides and their Applications in Photocatalysts and Electrode Materials. Australia is a world-leading producer of raw materials of many metallic elements, most of which are exported at low-values. This project will yield important knowledge in new synthetic techniques for making nanostructures of metal oxides. These tiny particles already have a large worldwide market, but the discovery of particles with superior properties or new applications could lead to new industries and high-value exports. This project aims to devise novel photocatalysts for solar energy conversion and environmental protection, and electrode materials for lithium batteries. It will contribute to the overall competitiveness and productivity of Australian R&D by advancing scientific knowledge and training young researchers.Read moreRead less
Mixing the jigsaw pieces of natural products: new molecules-new properties. This project aims to examine the capacity of exploiting the bacterial biosynthetic machinery to fast-track access to analogues of natural products. Due to increased drug resistance, new reservoirs of natural products are needed for evaluation as future drugs. Desferrioxamine B will be used as a model natural product to establish the biosynthesis of new analogues in bacterial culture supplemented with unsaturated, fluorin ....Mixing the jigsaw pieces of natural products: new molecules-new properties. This project aims to examine the capacity of exploiting the bacterial biosynthetic machinery to fast-track access to analogues of natural products. Due to increased drug resistance, new reservoirs of natural products are needed for evaluation as future drugs. Desferrioxamine B will be used as a model natural product to establish the biosynthesis of new analogues in bacterial culture supplemented with unsaturated, fluorinated or deuterated building blocks. The intended outcomes are to deliver advances in methods for generating structurally diverse pools of natural products, new label-free probes, knowledge of natural product biosynthesis, and excellence in training research students in frontier methods in chemical biology and drug discovery.Read moreRead less
Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has ....Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has potential application in biosensors and biocatalysis.Read moreRead less
Light driven supramolecular reactors. A major problem facing synthetic chemistry is how to control chemical reactivity using benign techniques. The aim of this project is to form supramolecular capsules that can bind guest molecules and use visible light to drive chemical reactions inside these cages. This project aims to develop the first examples of molecular cages that are able to catalyse photoredox processes. These enantiopure, self-assembled cages will be based on ruthenium(II) complexes w ....Light driven supramolecular reactors. A major problem facing synthetic chemistry is how to control chemical reactivity using benign techniques. The aim of this project is to form supramolecular capsules that can bind guest molecules and use visible light to drive chemical reactions inside these cages. This project aims to develop the first examples of molecular cages that are able to catalyse photoredox processes. These enantiopure, self-assembled cages will be based on ruthenium(II) complexes with established photophysical properties. The expected outcomes will include the first proof-of-principle examples of controlled photoredox reactions, opening the door for the development of enantioselective molecular photoreactors.Read moreRead less
Metal complexes for sustainable light-driven synthesis. The aim of this project is to use cheap, abundant transition metal ions and visible light to enable challenging synthetic chemical reactions. The significant problems addressed are that most synthetic reactions using visible light currently require expensive precious metals, and fundamental reaction pathways used by Nature remain inaccessible. Both of these problems limit the scope of synthetic applications. The outcomes will be new knowled ....Metal complexes for sustainable light-driven synthesis. The aim of this project is to use cheap, abundant transition metal ions and visible light to enable challenging synthetic chemical reactions. The significant problems addressed are that most synthetic reactions using visible light currently require expensive precious metals, and fundamental reaction pathways used by Nature remain inaccessible. Both of these problems limit the scope of synthetic applications. The outcomes will be new knowledge and sustainable technologies that can better harness visible light for useful synthetic chemistry applications. The benefits will be more efficient and cost-effective routes to valuable molecules ubiquitous in everyday life.Read moreRead less
Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Iron is essential for life, but iron-overload is a potentially fatal condition. There is no natural mechanism to excrete iron in humans, so patients suffering from iron-overload disorders are treated with the chelator Desferal to enable iron excretion typically from an early age. Desferal is orally ineffective and must be given by subcutaneous infusion (12-24h, 5-6 days/week) resulting in poor patient c ....Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Iron is essential for life, but iron-overload is a potentially fatal condition. There is no natural mechanism to excrete iron in humans, so patients suffering from iron-overload disorders are treated with the chelator Desferal to enable iron excretion typically from an early age. Desferal is orally ineffective and must be given by subcutaneous infusion (12-24h, 5-6 days/week) resulting in poor patient compliance. We will conduct critical chemical and biological experiments with a new series of potentially orally active iron chelators identified in our lab. The results from this project will be vital for the development of these compounds as pharmaceuticals.Read moreRead less