Three-dimensional structure determination of biomolecular assemblies from sparse data of different length scales. New computer algorithms will be combined with sparse experimental structure restraints, obtained with novel protein chemistry technologies, to generate accurate three-dimensional (3D) models of proteins and protein assemblies in solution and in the solid state. The new strategies will greatly increase the number of protein targets amenable to rational drug design.
Tags and algorithms for studies of protein structures and interactions. This project aims to develop a new set of tools to structurally characterise protein-protein and protein-ligand interactions that are difficult or impossible to analyse by other means, facilitate tracking of proteins in biological material and identify interaction partners. The project seeks to focus on the synthesis of new unnatural amino acids and tags for site-specific protein labelling, and a range of techniques for 3D s ....Tags and algorithms for studies of protein structures and interactions. This project aims to develop a new set of tools to structurally characterise protein-protein and protein-ligand interactions that are difficult or impossible to analyse by other means, facilitate tracking of proteins in biological material and identify interaction partners. The project seeks to focus on the synthesis of new unnatural amino acids and tags for site-specific protein labelling, and a range of techniques for 3D structure analysis in solution, in particular NMR spectroscopy. New algorithms are expected to be developed for optimizing NMR spectroscopy and structure calculations from sparse data. The integrated set of tools is expected to deliver better and faster structure analysis and target characterisation to accelerate early stages of drug discovery.Read moreRead less
Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collecti ....Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collection of structure restraints by nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and mass spectrometry, which are needed to generate accurate models of proteins and their complexes with other molecules. Major beneficial outcome will include an increase in the number of protein targets amenable to rational drug design and improved methods for generating new drug leads.Read moreRead less
Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE240100054
Funder
Australian Research Council
Funding Amount
$1,341,398.00
Summary
Dedicated High-throughput 3D-Electron Diffractometer. This proposal aims to install the first dedicated high-throughput 3D-electron diffractometer in the Southern Hemisphere, and one of the first in the world. It will be able to rapidly solve the atomic-scale structures of molecules and materials for which this is now extremely difficult and time-consuming – or impossible – due to the inability to grow large enough crystals for traditional X-ray diffraction. It will thus provide a significant ad ....Dedicated High-throughput 3D-Electron Diffractometer. This proposal aims to install the first dedicated high-throughput 3D-electron diffractometer in the Southern Hemisphere, and one of the first in the world. It will be able to rapidly solve the atomic-scale structures of molecules and materials for which this is now extremely difficult and time-consuming – or impossible – due to the inability to grow large enough crystals for traditional X-ray diffraction. It will thus provide a significant advantage for chemists, physicists, biologists, geologists, and engineers who rely on detailed structural knowledge to rationally optimise the properties of their compounds, from pharmaceutical activity to carbon capture to superconductivity, to the substantial benefit of multiple national priority areas.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100195
Funder
Australian Research Council
Funding Amount
$1,000,000.00
Summary
Field-emission gun transmission electron microscope for the research in nanomaterials, metal alloys and biological sciences. The proposed facility is required by a large range of world-leading research programs in light metals, nanomaterials, fibres and biomaterials. These research programs are strongly supported by automobile, textile, mineral and advanced materials industries that have important roles in the current national economy and local communities. The facility will improve significan ....Field-emission gun transmission electron microscope for the research in nanomaterials, metal alloys and biological sciences. The proposed facility is required by a large range of world-leading research programs in light metals, nanomaterials, fibres and biomaterials. These research programs are strongly supported by automobile, textile, mineral and advanced materials industries that have important roles in the current national economy and local communities. The facility will improve significantly our current research ability and help the creation of new research areas in nanotechnology and energy materials beneficial to clean energy, environmental protections and health care. It is also important equipment for new research student training.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100193
Funder
Australian Research Council
Funding Amount
$590,000.00
Summary
Next Generation Mass Spectrometry for Analysis of Biomolecules. Next-generation mass spectrometry for analysis of biomolecules:
This project seeks to establish a next-generation mass spectrometer that represents the most sensitive, accurate and rapid mass spectrometer allowing the simultaneous quantitation of several hundred to several thousand proteins in a single experiment. This is designed to particularly support infection and immunity research. Novel fragmentation capabilities and enhanced ....Next Generation Mass Spectrometry for Analysis of Biomolecules. Next-generation mass spectrometry for analysis of biomolecules:
This project seeks to establish a next-generation mass spectrometer that represents the most sensitive, accurate and rapid mass spectrometer allowing the simultaneous quantitation of several hundred to several thousand proteins in a single experiment. This is designed to particularly support infection and immunity research. Novel fragmentation capabilities and enhanced workflows on this instrument may allow new types of experiments to be conducted providing significant improvements in coverage and depth of analysis.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100122
Funder
Australian Research Council
Funding Amount
$725,000.00
Summary
Hydrogen-deuterium exchange system - a missing link in protein analysis . Proteins are highly dynamic molecules that are essential to life. This project aims to acquire a fully automated and integrated hydrogen-deuterium exchange system, a powerful tool for analysing the motion of proteins and their interactions with other molecules. Expected outcomes include a new capability for biology labs around Australia by (1) increasing success rates of difficult projects that aim to visualise 3D protein ....Hydrogen-deuterium exchange system - a missing link in protein analysis . Proteins are highly dynamic molecules that are essential to life. This project aims to acquire a fully automated and integrated hydrogen-deuterium exchange system, a powerful tool for analysing the motion of proteins and their interactions with other molecules. Expected outcomes include a new capability for biology labs around Australia by (1) increasing success rates of difficult projects that aim to visualise 3D protein structures and (2) providing rapid information about protein interaction sites. Anticipated benefits include the generation of dynamic data that will be highly complementary to static pictures of protein structures. This will enable clever design of new proteins with beneficial uses in the biotechnology industry.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0346515
Funder
Australian Research Council
Funding Amount
$507,000.00
Summary
Fluorescence Detector for the Australian National Beamline Facility. X-ray absorption spectroscopy (XAS) is an extremely important synchrotron radiation tool for determining the local structure around an X-ray absorbing atom. This has many applications in the study of materials, minerals, metal complexes, and metalloproteins and can often be used to obtain information that is not available by other techniques, because structural information can be obtained in the solid or solution state and in ....Fluorescence Detector for the Australian National Beamline Facility. X-ray absorption spectroscopy (XAS) is an extremely important synchrotron radiation tool for determining the local structure around an X-ray absorbing atom. This has many applications in the study of materials, minerals, metal complexes, and metalloproteins and can often be used to obtain information that is not available by other techniques, because structural information can be obtained in the solid or solution state and in mixtures. The current proposal is aimed at introducing new technology into the Australian National Beamline Facility that will greatly improve the quality and quantity of experiments that can be performed and extend studies into dilute solutions and protein samples.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453426
Funder
Australian Research Council
Funding Amount
$235,000.00
Summary
Access for Australian Researchers to Advanced Neutron Beam Techniques. Neutron scattering is one of the most powerful and important investigative tools in the study of materials. Australia has only a low-flux neutron source, HIFAR, which provides no cold or hot neutrons. This excludes large, important areas of science, such as functional films, polymers, self-assembly systems, biological materials, colloids and emulsions, and real-time in-situ studies.
This application aims to continue Australi ....Access for Australian Researchers to Advanced Neutron Beam Techniques. Neutron scattering is one of the most powerful and important investigative tools in the study of materials. Australia has only a low-flux neutron source, HIFAR, which provides no cold or hot neutrons. This excludes large, important areas of science, such as functional films, polymers, self-assembly systems, biological materials, colloids and emulsions, and real-time in-situ studies.
This application aims to continue Australia's partnership with the world's most intense neutron source, ISIS in the UK, in order to sustain the considerable Australian scientific momentum which now relies on ISIS.
The outcomes will be new science that cannot be generated solely within Australia.
Read moreRead less