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
Drug targets in malaria parasites. Malaria is rampant throughout our Region and hinders the economies of our neighbours reducing regional prosperity and stability. Australian security and aid personnel deployed in the Region contract malaria infections and global warming could bring malaria-carrying mosquitoes south to Sydney. Australia is pre-eminent in malaria research, making lead discoveries in vaccine and drug development. However, we lack crucial resources to study the parasite in the mo ....Drug targets in malaria parasites. Malaria is rampant throughout our Region and hinders the economies of our neighbours reducing regional prosperity and stability. Australian security and aid personnel deployed in the Region contract malaria infections and global warming could bring malaria-carrying mosquitoes south to Sydney. Australia is pre-eminent in malaria research, making lead discoveries in vaccine and drug development. However, we lack crucial resources to study the parasite in the mosquito phase of its life cycle. The Federation Fellowship will create a malaria mosquito facility to redress this crucial gap in our capability. The Fellowship will double as foreign aid investment by enhancing our capacity to protect ourselves as well as supporting our neighbours.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
Coherent X-ray Science and Biophysics. The twenty first century is said to be the century of biology. And there is no doubt that the development of our understanding of biological system is continuing at a massive rate. However, as our understanding deepens, we need to draw on the whole range of scientific disciplines to proceed. This program draws together a multidisciplinary team of world-leading scientists to address one the key questions in modern biology, the structure of a membrane protein ....Coherent X-ray Science and Biophysics. The twenty first century is said to be the century of biology. And there is no doubt that the development of our understanding of biological system is continuing at a massive rate. However, as our understanding deepens, we need to draw on the whole range of scientific disciplines to proceed. This program draws together a multidisciplinary team of world-leading scientists to address one the key questions in modern biology, the structure of a membrane protein. We will develop techniques based on the latest developments in theoretical physics & chemistry, imaging, biology and technology - including the new Australian Synchrotron - to create new approaches to structural biology.Read moreRead less
New Membrane Chips For Protein Interaction Analysis. This proposal is based on a strategic partnership between Monash University and Farfield Sensors. We will create a series of new biosensors that will be used to establish a new approach to the structural analysis of membrane protein function. In particular, this technology may lead to the identification of new proteins and drug targets for therapeutic development. The long-term outcome would be the development of improved therapeutics which wo ....New Membrane Chips For Protein Interaction Analysis. This proposal is based on a strategic partnership between Monash University and Farfield Sensors. We will create a series of new biosensors that will be used to establish a new approach to the structural analysis of membrane protein function. In particular, this technology may lead to the identification of new proteins and drug targets for therapeutic development. The long-term outcome would be the development of improved therapeutics which would be coupled to potential economic returns when further commercialisation is achieved. Read moreRead less
Intrinsically Unstructured Proteins (IUPs): NMR characterization, prediction, and application to malarial proteome. Determination of protein structures with longer DR by NMR will enrich the DR dataset and provide a deeper understanding of protein structure-function relationships and protein folding pathways. The proposal will also provide valuable information in the key applied area of target selection in structural biology. Not all current web services are freely accessible and available servi ....Intrinsically Unstructured Proteins (IUPs): NMR characterization, prediction, and application to malarial proteome. Determination of protein structures with longer DR by NMR will enrich the DR dataset and provide a deeper understanding of protein structure-function relationships and protein folding pathways. The proposal will also provide valuable information in the key applied area of target selection in structural biology. Not all current web services are freely accessible and available services can be improved further by using more reliable training dataset or more effective algorithms, development of a national DR predictor will help Australian structural biologists increase the success rate of structure determination and provide greater insight into a range of proteomes.Read moreRead less
Special Research Initiatives - Grant ID: SR0354892
Funder
Australian Research Council
Funding Amount
$40,000.00
Summary
The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these ....The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these enzymes. However this initiative aims to network their efforts by value-adding to the current protease research through promoting national and international collaborations to improve our understanding of biology, and encourage exploitation of proteases/inhibitors/receptors for pharmaceutical and industrial applications.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775679
Funder
Australian Research Council
Funding Amount
$700,000.00
Summary
Advanced Microscopy Infrastructure for use in Frontier Technologies. This proposal seeks to establish key microscopy facilities to support the research projects from leading researchers from four major Universities. The new facilities build on the close collaborative links between the partner organisations and the request is for specialised equipment that is complementary to that available at, for example, the Australian Synchrotron. The new facilities will enhance progress in the the important ....Advanced Microscopy Infrastructure for use in Frontier Technologies. This proposal seeks to establish key microscopy facilities to support the research projects from leading researchers from four major Universities. The new facilities build on the close collaborative links between the partner organisations and the request is for specialised equipment that is complementary to that available at, for example, the Australian Synchrotron. The new facilities will enhance progress in the the important areas of nanotechnology, biotechnology and advanced materials to the benefit of the community and will play a crucial role in training the next generation of researchers to drive these critical areas of science and technology.Read moreRead less