Radical redox indicators. This project aims to synthesise the first examples of advanced biological imaging agents that can reversibly respond to the oxidative status of living cells. Novel mitochondrially-targeted, fluorescent probes will be derived from several well-established families of biological dyes through the introduction of a stable free radical within the parent structure. The design of the new imaging agents aims to both enhance retention in, and restrict the fluorescence response t ....Radical redox indicators. This project aims to synthesise the first examples of advanced biological imaging agents that can reversibly respond to the oxidative status of living cells. Novel mitochondrially-targeted, fluorescent probes will be derived from several well-established families of biological dyes through the introduction of a stable free radical within the parent structure. The design of the new imaging agents aims to both enhance retention in, and restrict the fluorescence response to, the mitochondria so that changes in oxidation and reduction can be monitored. The probes will provide an innovative new means to assess reactive species and associated oxidative stress, thus delivering a new methodology to aid research into mitochondrial chemical biology.Read moreRead less
Emergent organocopper complexes as robust catalysts for electrosynthesis. The capture and stabilisation of highly reactive chemical species is critical to making advances in the synthesis of novel materials, agrochemicals and pharmaceuticals. Metal-bound carbanions are essential components of carbon-carbon bond forming reactions. This project aims to develop an unprecedented family of copper catalysts and deliver an innovative and versatile chemical reactivity platform. Expected outcomes of this ....Emergent organocopper complexes as robust catalysts for electrosynthesis. The capture and stabilisation of highly reactive chemical species is critical to making advances in the synthesis of novel materials, agrochemicals and pharmaceuticals. Metal-bound carbanions are essential components of carbon-carbon bond forming reactions. This project aims to develop an unprecedented family of copper catalysts and deliver an innovative and versatile chemical reactivity platform. Expected outcomes of this project include methods of tempering and unleashing the high reactivity of these species by controlling the oxidation state of the copper ion. Benefits of these outcomes include fundamental understanding of the reactivity of a new class of copper complex that has potential commercial applications in catalysis.Read moreRead less
Nanoarchitectured multifunctional porous superparamagnetic nanoparticles. This project aims to develop a method for the direct detection of biomarkers based on a new class of highly porous superparamagnetic nanoparticles with peroxidase-like activity. The particles will be used as dispersible capture agents for isolating specific targets in biological samples, and electrocatalytic nanozymes for naked-eye evaluation and electrochemical detection. The project is expected to develop simple, low-cos ....Nanoarchitectured multifunctional porous superparamagnetic nanoparticles. This project aims to develop a method for the direct detection of biomarkers based on a new class of highly porous superparamagnetic nanoparticles with peroxidase-like activity. The particles will be used as dispersible capture agents for isolating specific targets in biological samples, and electrocatalytic nanozymes for naked-eye evaluation and electrochemical detection. The project is expected to develop simple, low-cost, portable devices for the analysis of exosomes and exosomal miRNA in biological samples. The future development of this technology into diagnostic devices will improve patient outcomes by enabling earlier disease diagnosis and improved monitoring of treatment.Read moreRead less
Eradicating bacterial biofilms with nitroxide-antimicrobial hybrids. This project aims to develop new antimicrobials to address the rise of drug-resistant infections and resilient bacterial communities called biofilms. We aim to break new ground in our fundamental knowledge of antimicrobial mechanisms and exploit this understanding by fusing cellular/molecular microbiology and synthetic chemistry approaches. We seek to gain an in-depth understanding of how nitroxides induce bacterial biofilm dis ....Eradicating bacterial biofilms with nitroxide-antimicrobial hybrids. This project aims to develop new antimicrobials to address the rise of drug-resistant infections and resilient bacterial communities called biofilms. We aim to break new ground in our fundamental knowledge of antimicrobial mechanisms and exploit this understanding by fusing cellular/molecular microbiology and synthetic chemistry approaches. We seek to gain an in-depth understanding of how nitroxides induce bacterial biofilm dispersal, which is critical for the discovery of anti-biofilm molecules that do not fail due to resistance development. These breakthroughs should induce a step-change in our ability to reduce the occurrence of biofilm-related infection in fields ranging from medical and veterinary to biotechnology and agriculture.Read moreRead less
Bespoke nanomaterials for understanding nano-bio interactions under flow. This project aims to develop innovative scalable synthesis techniques to produce polymeric nanomaterials with controlled properties and characterise interactions between nanomaterials and cells under flow conditions. This project expects to generate new knowledge in priority research areas of nanotechnology, polymer chemistry and immunology. The outcome of this project is an original scalable and environmentally friendly t ....Bespoke nanomaterials for understanding nano-bio interactions under flow. This project aims to develop innovative scalable synthesis techniques to produce polymeric nanomaterials with controlled properties and characterise interactions between nanomaterials and cells under flow conditions. This project expects to generate new knowledge in priority research areas of nanotechnology, polymer chemistry and immunology. The outcome of this project is an original scalable and environmentally friendly technology, new knowledge of cell-nanomaterial interactions and new design principles for nanoparticles with potential future applications in drug delivery, immunology and nanomedicine. This project should provide significant benefits to polymer, nanomaterial and pharmaceutical research and industry in Australia.Read moreRead less
Controllable Synthesis of Defects in Catalysts for Electrocatalysis . This project aims to address the most critical issue of electrocatalysis: identification of active sites for carbon-based metal free catalysts (CMFCs). Through the development of new methodologies, this proposal will, for the first time, controllably synthesise the vacancy defects that are the major active sites for CMFCs. The expected outcomes from this project include in-depth understanding of the fundamentals of electrocata ....Controllable Synthesis of Defects in Catalysts for Electrocatalysis . This project aims to address the most critical issue of electrocatalysis: identification of active sites for carbon-based metal free catalysts (CMFCs). Through the development of new methodologies, this proposal will, for the first time, controllably synthesise the vacancy defects that are the major active sites for CMFCs. The expected outcomes from this project include in-depth understanding of the fundamentals of electrocatalysis: the reactivity of active sites and the catalytic performance with the number of active sites; which will not only significantly advance knowledge but also achieve breakthrough technologies that greatly benefit to the society and economy both for Australia and worldwide.Read moreRead less
Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for ....Harnessing molecular strain for drug discovery and bioconjugation. Peptides and proteins are increasingly important therapies for the treatment of disease. Nevertheless, the synthesis and optimisation of these high-value compounds still relies primarily on technologies developed decades ago. There is a desperate need for modern strategies to unlock the full potential of peptides and proteins for diverse applications in drug discovery. This interdisciplinary research aims to develop new tools for the construction and modification of peptides and proteins by harnessing the energy in a unique class of strained molecules. A focus on peptide-based inhibitors of the proteasome, a critical target for modern cancer treatments, should provide future health and economic benefits for the Australian community.Read moreRead less
Precision-built dynamic and functional polymer vesicles. The project aims to create new precision-built polymer vesicles with controlled size, stability, functionality and environmental responsiveness to mimic some of the key dynamic functions of the cell. The project expects to generate new knowledge on the dynamic interplay between the polymer and its bilayer including on-demand activated polymerisations and reactions, logic gates and in situ sensors. Expected outcomes of this project include ....Precision-built dynamic and functional polymer vesicles. The project aims to create new precision-built polymer vesicles with controlled size, stability, functionality and environmental responsiveness to mimic some of the key dynamic functions of the cell. The project expects to generate new knowledge on the dynamic interplay between the polymer and its bilayer including on-demand activated polymerisations and reactions, logic gates and in situ sensors. Expected outcomes of this project include new synthetic polymer techniques and new quantitative insights into the role of compartmentalisation on chemical reactions and polymerisations. This project will provide fundamental knowledge on bio/polymer vesicles with great potential to advance the polymer industry in Australia.Read moreRead less
Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic be ....Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic benefits for the Australian community, including: the first approach to a class of promising antibiotic peptide natural product analogues, the development of a mild electrochemical approach to peptide modification, and the production of a library of novel amino acids for incorporation into potential antibiotic leads.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