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
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
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
Integration of Electrochemistry and Green Chemistry: A Roadmap for Scientific Innovation. Electrochemistry represents an enabling science in physical, chemical and life sciences. It plays a key role in fundamental studies and in Australia's industrial capacity to exploit emerging technologies. Research conducted synergistically within the ARC Centre for Green Chemistry would enable the Monash Electrochemistry Group to develop and exploit new concepts. In the national interest, the Fellowship ....Integration of Electrochemistry and Green Chemistry: A Roadmap for Scientific Innovation. Electrochemistry represents an enabling science in physical, chemical and life sciences. It plays a key role in fundamental studies and in Australia's industrial capacity to exploit emerging technologies. Research conducted synergistically within the ARC Centre for Green Chemistry would enable the Monash Electrochemistry Group to develop and exploit new concepts. In the national interest, the Fellowship would: facilitate global participation in cutting-edge science derived from electrochemical and green chemical concepts; provide commercial opportunities for new and mature chemical industries; expand postgraduate training; and promote technology exchange with Australian and international leading-edge research organisations.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
Large amplitude Fourier transformed voltammetry: paths towards more efficient data evaluation strategies, enhanced insights and innovation in dynamic electrochemistry. Electrochemistry represents an enabling discipline in many branches of science. The aim of this research is to integrate the collective skills of an international consortium of experts in electrochemistry, electrical engineering, computing and mathematics in order to implement a blueprint proposed for innovation in electrochemic ....Large amplitude Fourier transformed voltammetry: paths towards more efficient data evaluation strategies, enhanced insights and innovation in dynamic electrochemistry. Electrochemistry represents an enabling discipline in many branches of science. The aim of this research is to integrate the collective skills of an international consortium of experts in electrochemistry, electrical engineering, computing and mathematics in order to implement a blueprint proposed for innovation in electrochemical science. In the national interest, the project will facilitate global participation in cutting-edge science derived from electrochemical concepts, provide commercial opportunities in the area of scientific instrumentation and promote technology exchange with Australian and international leading-edge research organizations.Read moreRead less
A blueprint for an intelligent instrumental, theoretical and experimental unification of a myriad of voltammetric and related electrochemical techniques. Electrochemistry is a prominent discipline in many areas of fundamental and applied science (for example, electron transfer reactions, corrosion, sensors, photovoltaics). The aim of the research proposal is to utilise skills available at Monash University and those of a national and international consortium of experts in electrochemistry, elec ....A blueprint for an intelligent instrumental, theoretical and experimental unification of a myriad of voltammetric and related electrochemical techniques. Electrochemistry is a prominent discipline in many areas of fundamental and applied science (for example, electron transfer reactions, corrosion, sensors, photovoltaics). The aim of the research proposal is to utilise skills available at Monash University and those of a national and international consortium of experts in electrochemistry, electrical engineering, computing and mathematics to introduce a new integrated instrumental, theoretical and experimental concept that will provide a blueprint for innovation in electrochemical science. An expected outcome is that important advances relevant to Australian Industry will be achieved in the area of scientific instrumentation and in modern applications of electrochemistry.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