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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560658
Funder
Australian Research Council
Funding Amount
$481,533.00
Summary
Shared Laser Facility. The Australian Shared Laser Facility (ASLF) has been providing lasers for physical chemistry research for a decade. ASLF lasers are portable and are transported between participating laboratories according to need and research priorities. Funds are sought to expand the ASLF by 3 laser systems and 2 research groups. The requested lasers provide mid-IR and deep UV wavelengths, spectral regions inaccessible with existing ASLF lasers. Access to these wavelengths is essenti ....Shared Laser Facility. The Australian Shared Laser Facility (ASLF) has been providing lasers for physical chemistry research for a decade. ASLF lasers are portable and are transported between participating laboratories according to need and research priorities. Funds are sought to expand the ASLF by 3 laser systems and 2 research groups. The requested lasers provide mid-IR and deep UV wavelengths, spectral regions inaccessible with existing ASLF lasers. Access to these wavelengths is essential for Australian research to remain at the forefront of international physical chemistry research. ASLF laboratories support a wide range of chemical research including spectroscopy, environmental chemistry, astrochemistry, and exploration of nanostructured materials.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883030
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
High-Resolution Field Emission Scanning Electron Microscopy (FESEM) Platform for Characterisation at the Nanometre-Level. The Field Emission Scanning Electron Microscope (FESEM) is designed to provide fundamental insights into physical and biological systems though characterisation and analysis of structures on nanometre length scales. This versatile instrument will support a wide range of research projects covering all four national research priorities. These range from the characterisation of ....High-Resolution Field Emission Scanning Electron Microscopy (FESEM) Platform for Characterisation at the Nanometre-Level. The Field Emission Scanning Electron Microscope (FESEM) is designed to provide fundamental insights into physical and biological systems though characterisation and analysis of structures on nanometre length scales. This versatile instrument will support a wide range of research projects covering all four national research priorities. These range from the characterisation of light alloys to boost and intensify Australia's aluminium, magnesium and titanium alloy industries, to tissue engineering for the repair of human elastic tissues in skin, artery, bladder and lung, to the study of microtubules in plant cells for genetic manipulation of plants to withstand environmental stresses such as drought or salinity.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
Electro-active and migratory peptides in lipid bilayers: NMR and biophysical studies. All living things are characterized by the separation of inner space from the surrounding medium by a self-assembling membrane. Selective entry and exit of water, ions and solutes is a defining feature of each type of cell. Some proteins sense the voltage difference across the cell membrane and open or close in response to voltage changes. Others, like bacterial toxins assemble in the membrane as pores, while o ....Electro-active and migratory peptides in lipid bilayers: NMR and biophysical studies. All living things are characterized by the separation of inner space from the surrounding medium by a self-assembling membrane. Selective entry and exit of water, ions and solutes is a defining feature of each type of cell. Some proteins sense the voltage difference across the cell membrane and open or close in response to voltage changes. Others, like bacterial toxins assemble in the membrane as pores, while other peptides migrate across the membrane piggy-backing their peptide cargo. The aim is to understand the molecular mechanisms in examples of these membrane-active peptides and proteins with a view to enabling rational intervention into their operation in situ in normal and disease states.Read moreRead less
NMR studies of membrane proteins and peptides in novel amphiphilic mesophases. Membrane proteins are the next frontier in structural biology. Our goal is the structural and mechanistic characterization of the proteins and peptides from platypus venom and a cardiac potassium ion channel, HERG, that has a particular role in the suppression of cardiac arrhythmias. To do this we will refine and develop methods using amphiphilic mesophases and micelles and state-of-the-art NMR spectroscopy. Electrop ....NMR studies of membrane proteins and peptides in novel amphiphilic mesophases. Membrane proteins are the next frontier in structural biology. Our goal is the structural and mechanistic characterization of the proteins and peptides from platypus venom and a cardiac potassium ion channel, HERG, that has a particular role in the suppression of cardiac arrhythmias. To do this we will refine and develop methods using amphiphilic mesophases and micelles and state-of-the-art NMR spectroscopy. Electrophysiological analysis of ion channels and interactions with toxins will relate NMR structures to function. The NMR methodologies we develop will have broad applicability to membrane proteins in general.
Read moreRead less
Surface adsorption, repulsion and attraction: A new experimental approach to surface forces. The ability to understand and manipulate the stability of finely dispersed particles (colloids) in water is essential to modern living. It is necessary in processes as diverse as water purification, minerals separation, food and paper production. The behaviour of the colloidal system can often be understood in terms of the interaction between the dispersed particles. This project aims to improve our abil ....Surface adsorption, repulsion and attraction: A new experimental approach to surface forces. The ability to understand and manipulate the stability of finely dispersed particles (colloids) in water is essential to modern living. It is necessary in processes as diverse as water purification, minerals separation, food and paper production. The behaviour of the colloidal system can often be understood in terms of the interaction between the dispersed particles. This project aims to improve our ability to predict the nature of the interaction between dispersed particles, through an understanding of the events at a particle surface during a collision with another particle. This will enable us to better understand and control real colloidal systems.Read moreRead less
Nuclear magnetic resonance (NMR) studies of complex cellular responses: isotopomer sub-spaces, 'lost' ATP and 'tunable' anisotropy. Red blood cells (RBCs) transport oxygen around the body but they have other roles that are mediated by complex interconnecting metabolic pathways that generate myriad metabolites including ATP. A longstanding conundrum is the inability to account for ~60% of ATP turnover in human RBCs. Processes that may consume this 'lost' ATP, include autonomous motion of the cel ....Nuclear magnetic resonance (NMR) studies of complex cellular responses: isotopomer sub-spaces, 'lost' ATP and 'tunable' anisotropy. Red blood cells (RBCs) transport oxygen around the body but they have other roles that are mediated by complex interconnecting metabolic pathways that generate myriad metabolites including ATP. A longstanding conundrum is the inability to account for ~60% of ATP turnover in human RBCs. Processes that may consume this 'lost' ATP, include autonomous motion of the cell membrane called 'flickering', and maintenance of the biconcave-disc shape. NMR spectroscopy of quadrupolar nuclei in chiral aligned media, and isotopomer analysis will be used to define the kinetics of metabolism and membrane processes and thus help define the molecular basis of major blood disorders. Read moreRead less