Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymera ....Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymerase. This project aims to define the inhibition mechanism and to evaluate a potential use of these compounds for antiviral drug development.Read moreRead less
Membrane structure and lipid interactions of the pore-forming toxin Equinatoxin II by NMR. The structure of Equinatoxin II, a pore-forming protein, will be determined in model cell membranes using solid-state NMR spectroscopy. The relationship of molecular structure to bioactivity and the nature of the pore-forming mechanism of this toxin will be determined. The results will aid in understanding how toxins lyse cells and could lead to the design of improved antibiotic peptides. Currently the st ....Membrane structure and lipid interactions of the pore-forming toxin Equinatoxin II by NMR. The structure of Equinatoxin II, a pore-forming protein, will be determined in model cell membranes using solid-state NMR spectroscopy. The relationship of molecular structure to bioactivity and the nature of the pore-forming mechanism of this toxin will be determined. The results will aid in understanding how toxins lyse cells and could lead to the design of improved antibiotic peptides. Currently the structure of membrane proteins are difficult to determine and the newly developed techniques used for the structural determination of this membrane-associated protein will be suitable for studying other membrane proteins and receptors of pharmaceutical importance.Read moreRead less
New polymerisation processes for the synthesis of novel biopolymers. Synthetic peptide-based vaccines, formed via polymerisation of small bioactive motifs, possess several advantages over traditional approaches and promise to be the multi-disease targeting vaccines of the future. Disease targets will include influenza and hepatitis C viruses and a toxin from enteropathogenic Escherichia coli. These three diseases are in desperate need of novel vaccine approaches and the chemistries described in ....New polymerisation processes for the synthesis of novel biopolymers. Synthetic peptide-based vaccines, formed via polymerisation of small bioactive motifs, possess several advantages over traditional approaches and promise to be the multi-disease targeting vaccines of the future. Disease targets will include influenza and hepatitis C viruses and a toxin from enteropathogenic Escherichia coli. These three diseases are in desperate need of novel vaccine approaches and the chemistries described in this proposal represent a conceptual leap over traditional, and so far ineffective approaches investigated thus far. Synthetic antifreeze proteins and bioelastomers will also be constructed using our catalysis driven polymerisation process and applied to unmet medical and industrial needs.Read moreRead less
New methods for the synthesis of stable cyclic peptides. This proposal will design, synthesise and evaluate novel carbocyclic analogues of cyclic peptides which have application in the treatment of pain, diabetes management, malaria, and cancer therapy and diagnosis. The carbocyclic analogues will have improved biostability and will also provide the opportunity for oral administration. Carbacyclic analogues of insulin could lead to improved treatment of Australia's 1.2 million diabetics includi ....New methods for the synthesis of stable cyclic peptides. This proposal will design, synthesise and evaluate novel carbocyclic analogues of cyclic peptides which have application in the treatment of pain, diabetes management, malaria, and cancer therapy and diagnosis. The carbocyclic analogues will have improved biostability and will also provide the opportunity for oral administration. Carbacyclic analogues of insulin could lead to improved treatment of Australia's 1.2 million diabetics including many Aboriginal Australians who are particularly susceptible to Type II diabetes and its debilitating complications.Read moreRead less
New analgesics based on µ-conotoxins: structure-based design of helical mimetics. Diseases in which voltage-gated sodium channels are implicated are contributors to morbidity and mortality in the Australian population, and this project promises to provide new leads for the future development of drugs to treat such diseases, in particular analgesics for the treatment of chronic pain. The generation of these leads will entail the development of new approaches to mimicking key regions of peptides a ....New analgesics based on µ-conotoxins: structure-based design of helical mimetics. Diseases in which voltage-gated sodium channels are implicated are contributors to morbidity and mortality in the Australian population, and this project promises to provide new leads for the future development of drugs to treat such diseases, in particular analgesics for the treatment of chronic pain. The generation of these leads will entail the development of new approaches to mimicking key regions of peptides and proteins in drug-like molecules. This is a highly interdisciplinary project, spanning structural biology, molecular design, medicinal chemistry, molecular biology and electrophysiology, and the training of PhD graduates with such broad experience represents another national benefit of the project.Read moreRead less
New Polymers for Cellulose-based Bioplastics. We will design new cellulose derivatives by combining carefully engineered synthetic polymers to cellulose. We will explore the fundamental science underpinning the manufacture of these bioplastics, and apply the concept to the design of two new materials, with (super)hydrophobic and antibacterial properties. These materials have the potential to replace synthetic plastics, which comprise one of the major outputs of the chemical industry worldwide. P ....New Polymers for Cellulose-based Bioplastics. We will design new cellulose derivatives by combining carefully engineered synthetic polymers to cellulose. We will explore the fundamental science underpinning the manufacture of these bioplastics, and apply the concept to the design of two new materials, with (super)hydrophobic and antibacterial properties. These materials have the potential to replace synthetic plastics, which comprise one of the major outputs of the chemical industry worldwide. Plastic is present everywhere in human life, but its manufacture and disposal have a strong negative impact on the environment; the new materials manufactured in this project are viable alternatives to plastics, and are sustainable from a production and disposal point of view.Read moreRead less
Reactivity and Spectroscopy of Gas Phase Metal Oxide Cluster Ions: Structure-Reactivity Correlations and Fundamental Insights into Heterogeneous Catalysis. This project will make use of world class ARC funded instrumentation to carry out breakthrough science. The research will contribute fundamental insights into chemical bond activation relevant to industrial catalytic processes important to national manufacturing industries. These insights will improve the efficiency and selectivity of catal ....Reactivity and Spectroscopy of Gas Phase Metal Oxide Cluster Ions: Structure-Reactivity Correlations and Fundamental Insights into Heterogeneous Catalysis. This project will make use of world class ARC funded instrumentation to carry out breakthrough science. The research will contribute fundamental insights into chemical bond activation relevant to industrial catalytic processes important to national manufacturing industries. These insights will improve the efficiency and selectivity of catalytic processes and lead to increased profitability and/or a reduction in unwanted side products and pollution. The project will train young scientists in important experimental and theoretical chemical techniques, and will enhance and contribute to Australia's international research profile.Read moreRead less
Dynamics of Photon-Induced Processes in Engineered Polymer Systems. This project will investigate photo-induced energy and electron transport in innovative polymer systems of well defined structure. New functionalised, aromatic and conjugated polymers will be synthesised and studied by ultrafast laser spectroscopic techniques. Information on the dynamics of light energy dissipation processes in these polymers on time-scales down to the femtosecond regime and at a single molecule level will be ....Dynamics of Photon-Induced Processes in Engineered Polymer Systems. This project will investigate photo-induced energy and electron transport in innovative polymer systems of well defined structure. New functionalised, aromatic and conjugated polymers will be synthesised and studied by ultrafast laser spectroscopic techniques. Information on the dynamics of light energy dissipation processes in these polymers on time-scales down to the femtosecond regime and at a single molecule level will be obtained. The results will provide the basic information required to develop novel photon-active materials and devices.Read moreRead less
The development of unique cyclic polymers. The project will yield cyclic polymers with a large range of commercial and industrial applications (e.g. drug delivery, contamination clean-up, nano-wires, sensors) that will result in positive economic and social benefits for Australia. The research will lead to increased employment opportunities within the manufacturing industry and R&D, and also underpin and extend Australia's leading position in the development of innovative polymeric and advanced ....The development of unique cyclic polymers. The project will yield cyclic polymers with a large range of commercial and industrial applications (e.g. drug delivery, contamination clean-up, nano-wires, sensors) that will result in positive economic and social benefits for Australia. The research will lead to increased employment opportunities within the manufacturing industry and R&D, and also underpin and extend Australia's leading position in the development of innovative polymeric and advanced materials. The resulting materials will provide new and improved technological innovations for commercial products, delivering benefits direct to the public. Furthermore, there is potential development of spin-off companies - leading to further investment in Australian science and industry.Read moreRead less
Macromolecular Self-Assembly of Amyloid Fibrils. The misfolding of proteins is a key issue in public health. Common diseases, such as Alzheimer's disease, type 2 diabetes, and heart disease are associated with protein misfolding, and have a major impact on society. The use of proteins as therapeutic drugs is now common ( e.g. as vaccines, for immune disorders) but they can be rendered ineffective or harmful by protein misfolding. Through this project, we will enhance the fundamental understandin ....Macromolecular Self-Assembly of Amyloid Fibrils. The misfolding of proteins is a key issue in public health. Common diseases, such as Alzheimer's disease, type 2 diabetes, and heart disease are associated with protein misfolding, and have a major impact on society. The use of proteins as therapeutic drugs is now common ( e.g. as vaccines, for immune disorders) but they can be rendered ineffective or harmful by protein misfolding. Through this project, we will enhance the fundamental understanding of the processes of protein assembly in solution, at solid surfaces, and under shear.
Read moreRead less