Enzyme-inspired polymer nanomaterials. This project aims to develop new chemical methods and polymers inspired by nature. Enzymes are nature’s catalysts: they recognise a substrate and bind with it to provide the optimal environment for a reaction. However, they are easily degraded, limiting their industrial use. This project aims to develop new, highly stable polymer designs that can perform similar functions. This will be achieved by using polymer and supramolecular chemistry to control the re ....Enzyme-inspired polymer nanomaterials. This project aims to develop new chemical methods and polymers inspired by nature. Enzymes are nature’s catalysts: they recognise a substrate and bind with it to provide the optimal environment for a reaction. However, they are easily degraded, limiting their industrial use. This project aims to develop new, highly stable polymer designs that can perform similar functions. This will be achieved by using polymer and supramolecular chemistry to control the reaction environment, in combination with computational techniques to explore observed reactivity and guide nanoenvironment design. Expected outcomes include new polymers and materials capable of controlling a range of reactions and expanding the scope of bioinspired polymer design.Read moreRead less
Discovery and applications of circular proteins. The many national benefits that will flow from this program include (i) new knowledge in plant biochemistry, peptide chemistry and protein engineering protected by a strong intellectual property position that will give Australia a competitive edge in relevant biotechnology applications; (ii) the training of a new generation of skilled researchers to drive a sustainable biotechnology sector in Australia; (iii) economic benefits from royalty returns ....Discovery and applications of circular proteins. The many national benefits that will flow from this program include (i) new knowledge in plant biochemistry, peptide chemistry and protein engineering protected by a strong intellectual property position that will give Australia a competitive edge in relevant biotechnology applications; (ii) the training of a new generation of skilled researchers to drive a sustainable biotechnology sector in Australia; (iii) economic benefits from royalty returns on drugs and agricultural products that will likely arise from the program; (iv) environment benefits due to a reduced need for chemical insecticides; and (v) social benefits due to a reduction in suffering from diseases for which drugs are developed as a result of this program.Read moreRead less
Pro-Fluorescent Aryl Nitroxides: New Probes for Polymer Lifetime and Kinetics Research. Internal aryl rings present in novel probes developed for this project impart fluorescence which is efficiently and internally quenched by the presence of a paramagnetic nitroxide group. Scavenging of radicals by the nitroxide however "switches on" the fluorescence and this enables powerful new fluorescence-based detection levels for the technique of nitroxide free radical scavenging. Such sensitivity is a ....Pro-Fluorescent Aryl Nitroxides: New Probes for Polymer Lifetime and Kinetics Research. Internal aryl rings present in novel probes developed for this project impart fluorescence which is efficiently and internally quenched by the presence of a paramagnetic nitroxide group. Scavenging of radicals by the nitroxide however "switches on" the fluorescence and this enables powerful new fluorescence-based detection levels for the technique of nitroxide free radical scavenging. Such sensitivity is applicable to polymerization kinetics studies, as well as providing new means for the determination of materials lifetimes. The development of pro-fluorescent markers as indicators for polymer degradation would be a significant outcome for materials where component failure has a major negative impact.Read moreRead less
Organophosphate pesticide degradation: evolved enzymes and biomimetics for bioremediation and medicine. Organophosphate (OP) pesticides are an indispensable part of modern agriculture - their use results in dramatically increased crop yields. However, they are toxic and can damage the environment and cause significant health problems. Enzymes are currently being used to treat runoff water that is contaminated with OPs. The same enzymes also have the potential to aid in the treatment of OP poison ....Organophosphate pesticide degradation: evolved enzymes and biomimetics for bioremediation and medicine. Organophosphate (OP) pesticides are an indispensable part of modern agriculture - their use results in dramatically increased crop yields. However, they are toxic and can damage the environment and cause significant health problems. Enzymes are currently being used to treat runoff water that is contaminated with OPs. The same enzymes also have the potential to aid in the treatment of OP poisoning. However, OP degrading enzymes could be improved in many ways - we will evolve these enzymes to enhance their catalytic properties - to enable them to act more efficiently on an increased number of OPs. Read moreRead less
Designing and Building Novel 2D Hybrid Materials. The aim of this project is to use computational and experimental techniques to discover and fabricate new hybrid materials. Single-layer (2-D) materials like graphene have gained prominence and new ones are constantly being reported. Hybrid materials built from combinations of 2-D layers are appearing but progress is slow. This project is designed to increase the rate of discovery and fabrication of hybrids. The outcome would be an extensive data ....Designing and Building Novel 2D Hybrid Materials. The aim of this project is to use computational and experimental techniques to discover and fabricate new hybrid materials. Single-layer (2-D) materials like graphene have gained prominence and new ones are constantly being reported. Hybrid materials built from combinations of 2-D layers are appearing but progress is slow. This project is designed to increase the rate of discovery and fabrication of hybrids. The outcome would be an extensive database of materials properties, clear direction on how to control material properties, and manufacturing protocols to build a wide range of new materials.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
Nitroxide-containing scaffolds for controlling biofilm-related infections. Bacterial biofilms are a major problem in healthcare systems around the world as they cause persistent and chronic infections, including those associated with medical implants and cystic fibrosis. This project aims to develop new chemical approaches to deliver nitroxides at surface interfaces and in microparticles to facilitate long term control over biofilm growth. It is expected that these functionalised scaffolds will ....Nitroxide-containing scaffolds for controlling biofilm-related infections. Bacterial biofilms are a major problem in healthcare systems around the world as they cause persistent and chronic infections, including those associated with medical implants and cystic fibrosis. This project aims to develop new chemical approaches to deliver nitroxides at surface interfaces and in microparticles to facilitate long term control over biofilm growth. It is expected that these functionalised scaffolds will represent a breakthrough in the field and will have a profound impact by reducing infection rates associated with medical devices and improving airway clearance in cystic fibrosis patients.Read moreRead less
Directed evolution of enzymes for bioremediation: structure function studies of bimetalloenzymes. We will evolve enzymes that degrade organophosphate pesticides (OPs) that are used in Australian agriculture. Although these OPs were designed to kill insects they are closely related to chemical warfare agents and are known to be toxic to humans. Bacteria have acquired a number of enzymes that degrade some OPs. One such enzyme has been used in field trials demonstrating its potential to degrade OP ....Directed evolution of enzymes for bioremediation: structure function studies of bimetalloenzymes. We will evolve enzymes that degrade organophosphate pesticides (OPs) that are used in Australian agriculture. Although these OPs were designed to kill insects they are closely related to chemical warfare agents and are known to be toxic to humans. Bacteria have acquired a number of enzymes that degrade some OPs. One such enzyme has been used in field trials demonstrating its potential to degrade OP residues. However, many pesticides are not removed rapidly and OP-degrading enzymes require modification(s) if they are to be useful environmental reagents - this can be achieved with directed evolution. Read moreRead less
Chemically re-engineering bioactive natural products using fragment based drug design. Current drug and agrichemical discovery technologies are under immense pressure to meet the future pharmaceutical and agriculture demand created by population growth. This project will develop a novel technology concept that re-engineers the chemical features of bioactive natural products optimising medicine and agrichemical discovery.
Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to mem ....Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to membrane potential changes. Recently reported crystal structures of bacterial Nav channels have greatly advanced the field, but these channels contain four identical VSDs and have different inactivation properties. Thus, much remains to be learnt about the conformational plasticity of eukaryotic Nav channel VSDs. The project plans to use animal toxins to capture eukaryotic VSDs in defined states of the gating cycle for detailed structural analysis using nuclear magnetic resonance and X-ray crystallography.Read moreRead less