New Surfaces for the Control of Endothelial Cell Function: Application in the Design of Biocompatible Stents. Using dewetting of thin polymer films, the present proposal will develop new structured biocompatible surfaces with controlled chemistry and topography, which will allow the growth of a normal (non-activated) monolayer of endothelial cells. Sophisticated molecular parameters will be used to assess that endothelial cells maintain their normal quiescent phenotype. The project sets the grou ....New Surfaces for the Control of Endothelial Cell Function: Application in the Design of Biocompatible Stents. Using dewetting of thin polymer films, the present proposal will develop new structured biocompatible surfaces with controlled chemistry and topography, which will allow the growth of a normal (non-activated) monolayer of endothelial cells. Sophisticated molecular parameters will be used to assess that endothelial cells maintain their normal quiescent phenotype. The project sets the ground work for the design of improved, more biocompatible structured stents to minimise the abnormal growth of cells on and around the stent, thereby reducing the occurrence of vascular complications. Thus this research could improve the success rate of stents implanted into patients with cardiovascular disease and reduce health costs.Read moreRead less
Chemical Insights to Peptide Helix-Sheet-Nanofibre Equilibria. We live in an ageing community that is experiencing exponential growth in neurological diseases that require full time carers and place significant burdens on our health system. Many such diseases are caused by (apparently) abnormal folding of proteins that aggregate into insoluble materials. The chemistry behind these processes is not sufficiently well understood to know precisely why the diseases are caused and how they might be tr ....Chemical Insights to Peptide Helix-Sheet-Nanofibre Equilibria. We live in an ageing community that is experiencing exponential growth in neurological diseases that require full time carers and place significant burdens on our health system. Many such diseases are caused by (apparently) abnormal folding of proteins that aggregate into insoluble materials. The chemistry behind these processes is not sufficiently well understood to know precisely why the diseases are caused and how they might be treated. This project will use new strategies to control peptide folding, provide important new information relevant to understanding such processes/diseases, and teach us how to engineer important new biomaterials that can advance nanotechnology. Read moreRead less
Design and discovery of novel conotoxins that target ion channels and receptors. The national benefits that may arise include (i) new knowledge of biologically active peptides and their mode of action that will be protected through patent applications and provide a competitive edge for Australian biotechnology (ii) the training of a new generation of skilled researchers in chemical and structural biology that will sustain the biotechnology industry (iii) economic benefits from licensing and roya ....Design and discovery of novel conotoxins that target ion channels and receptors. The national benefits that may arise include (i) new knowledge of biologically active peptides and their mode of action that will be protected through patent applications and provide a competitive edge for Australian biotechnology (ii) the training of a new generation of skilled researchers in chemical and structural biology that will sustain the biotechnology industry (iii) economic benefits from licensing and royalty returns on drug leads that may arise from this program (iv) environmental benefits from the development of more sensitive analytical methods that obviate over collection of endangered species and (v) social benefits from a reduction in suffering from diseases for which drugs are developed as a result of this program.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
Non-invasive diagnosis using micropatches that sample biomarkers from skin. We are developing a technology called the micropatch that is laid onto the surface of the skin. When the patch is pulled away, it retains proteins found in the subsurface skin layers. We believe that by analysing these proteins we will be able to diagnose diseases like cancer earlier and therefore have a better chance of treating them successfully. The process is painless, and doctors already use it to give drugs and vac ....Non-invasive diagnosis using micropatches that sample biomarkers from skin. We are developing a technology called the micropatch that is laid onto the surface of the skin. When the patch is pulled away, it retains proteins found in the subsurface skin layers. We believe that by analysing these proteins we will be able to diagnose diseases like cancer earlier and therefore have a better chance of treating them successfully. The process is painless, and doctors already use it to give drugs and vaccines. In the future we hope that our technology will be simple enough for routine diagnosis, even in the Outback where doctors are hundreds of kilometres awayRead 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: LE0775529
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Structural elucidation by chemical degradation mass spectrometry using a linear ion trap with electron transfer dissociation. The mass spectrometric instrumentation that we plan to acquire represents a true breakthrough in technology, and will be the first of its kind in operation in Australia. The instrument to be purchased will improve the ability of a wide cross section of researchers to characterize compounds important in fields as varied as medical research, agricultural biotechnology, and ....Structural elucidation by chemical degradation mass spectrometry using a linear ion trap with electron transfer dissociation. The mass spectrometric instrumentation that we plan to acquire represents a true breakthrough in technology, and will be the first of its kind in operation in Australia. The instrument to be purchased will improve the ability of a wide cross section of researchers to characterize compounds important in fields as varied as medical research, agricultural biotechnology, and natural product characterization. All types of chemical research, from fundamental to applied, will benefit from access to this system, which has clearly positive implications with regard to societal impact. Implementing this type of frontier technology is an essential step in maintaining the world class capabilities of the Australian research community.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0454008
Funder
Australian Research Council
Funding Amount
$340,962.00
Summary
Multi-function high resolution-analytical scanning electron microscope facility. The aim of this proposal is to establish a high resolution electron microscope facility as part of a comprehensive materials characterisation infrastructure required to support Swinburne's expanding activities in nanotechnology. A high resolution SEM in conjunction with an upgrade of the current SEM will provide advanced instrumentation for nanoscale imaging, analysis and manipulation of materials. The proposed faci ....Multi-function high resolution-analytical scanning electron microscope facility. The aim of this proposal is to establish a high resolution electron microscope facility as part of a comprehensive materials characterisation infrastructure required to support Swinburne's expanding activities in nanotechnology. A high resolution SEM in conjunction with an upgrade of the current SEM will provide advanced instrumentation for nanoscale imaging, analysis and manipulation of materials. The proposed facility will create new opportunities for collaborative programs with local and overseas researcher and will facilitate rapid progress in research programs across the entire University in particular those related to two ARC Centres of Excellence in which the University is a core partner.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