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
Integrated Multidimensional Gas Chromatography - Spectroscopic Detection Methodology for Chemical Marker Discovery. Chemical species are pervasive in our modern society and are found in personal care products, foods, additives, petroleum products, illicit drugs, pharmaceuticals and pollutants. Each sample must be analysed to determine its accurate composition, and as a safeguard. This requires chemical methods of analysis. Classical chemical methods may fail when samples become too complex, or t ....Integrated Multidimensional Gas Chromatography - Spectroscopic Detection Methodology for Chemical Marker Discovery. Chemical species are pervasive in our modern society and are found in personal care products, foods, additives, petroleum products, illicit drugs, pharmaceuticals and pollutants. Each sample must be analysed to determine its accurate composition, and as a safeguard. This requires chemical methods of analysis. Classical chemical methods may fail when samples become too complex, or they may lead to imprecise identification. This Frontier Technologies proposal has broad national and international relevance through development of new methods for authentication of chemical identity and the subsequent superior ability to characterise numerous sample compositions.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989615
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Melbourne Platform for Surface Characterisation of Structured Materials. The Australian economy is gradually expanding its manufacturing base through the development of the nanotechnology and biotechnology sectors. This will lead to production of a more diverse range of elaborately transformed goods. A key contributor to these export opportunities will be the nanotechnology sector since at the present time no country has a real nanotechnology based economy and there are many niche markets availa ....Melbourne Platform for Surface Characterisation of Structured Materials. The Australian economy is gradually expanding its manufacturing base through the development of the nanotechnology and biotechnology sectors. This will lead to production of a more diverse range of elaborately transformed goods. A key contributor to these export opportunities will be the nanotechnology sector since at the present time no country has a real nanotechnology based economy and there are many niche markets available for smaller countries such as Australia. This proposal helps to build quality control and characterisation infrastructure that will facilitate prototyping and design of nanoscale devices and sensors for next generation manufacturing.Read moreRead less
Raman and synchrotron spectroscopy of nano-scale drug interactions and molecular processes in single living cells. The need for potent low-cost drugs is ever increasing, yet effective ways to screen for new drugs remain elusive. A spectroscopic approach to screening drugs in living cells would seem a logical alternative to chemically based and morphological methods that are the status quo. In this context we are developing methodology to analyse molecular target sites in single living cells for ....Raman and synchrotron spectroscopy of nano-scale drug interactions and molecular processes in single living cells. The need for potent low-cost drugs is ever increasing, yet effective ways to screen for new drugs remain elusive. A spectroscopic approach to screening drugs in living cells would seem a logical alternative to chemically based and morphological methods that are the status quo. In this context we are developing methodology to analyse molecular target sites in single living cells for two of the most devastating diseases to afflict human kind, namely malaria and cancer. New ways of rapidly screening drugs in living cells prior to clinical trials will save an enormous amount of time, money and ultimately lives.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989127
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
A High-Throughput Neutron Spectrometer for The Study of Atomic and Molecular Motion at ANSTO. Neutron scattering enables new science across a broad range of disciplines, and for this reason it is undergoing major expansion in the USA, Europe, Japan and Australia. Various diffactometers and spectrometers have recently been built at ANSTO, but an instrumental option for a high-throughput cross-discipline spectroscopy is urgently needed. Fortunately, it is fairly straightforward to add this type of ....A High-Throughput Neutron Spectrometer for The Study of Atomic and Molecular Motion at ANSTO. Neutron scattering enables new science across a broad range of disciplines, and for this reason it is undergoing major expansion in the USA, Europe, Japan and Australia. Various diffactometers and spectrometers have recently been built at ANSTO, but an instrumental option for a high-throughput cross-discipline spectroscopy is urgently needed. Fortunately, it is fairly straightforward to add this type of option to an existing spectrometer that will broaden its user-base from specialised applications in physics to more general applications in physics, chemistry, materials-science and biology. This additional option provides a totally new way for Australian scientists to study atomic and molecular motions. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0237527
Funder
Australian Research Council
Funding Amount
$170,000.00
Summary
Bioscope IV : Advanced Scanned Probe Microscopy. The Atomic Force Microscope presents a unique view of the microscopic and molecular world, for it is sensitive to force alone. This instrument can accurately map force over a surface at the molecular scale; picoNewtons at nanometre resolution. The host of intermolecular forces which cause phenomena such as self-assembly, colloid stability, cell interactions and friction are only directly measurable with this technique. In this field of force meas ....Bioscope IV : Advanced Scanned Probe Microscopy. The Atomic Force Microscope presents a unique view of the microscopic and molecular world, for it is sensitive to force alone. This instrument can accurately map force over a surface at the molecular scale; picoNewtons at nanometre resolution. The host of intermolecular forces which cause phenomena such as self-assembly, colloid stability, cell interactions and friction are only directly measurable with this technique. In this field of force measurement Australian researchers are leaders. The proposed instrument expands the capabilities of this effort, and develops exciting new directions including the direct manipulation of molecules through a novel feedback and control (haptic) interface.Read moreRead less