3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, ....3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, and how they malfunction in disease. This project will provide a computational framework to increase the impact of this investment by integrating measurements from a range of novel technologies and developing understanding of changes in structure of large protein complexes in different functional states.Read moreRead less
Single Molecule Studies of Replisomal Function. It has recently become possible to watch the copying of DNA molecules with a specialized microscope in real time. This process requires assembly of a complex molecular machine on the DNA, followed by triggering of its function, and yields exquisitely detailed information about how the machine works. In this new collaboration between scientists in Australia and the U.S.A., we will assemble these machines on single DNA molecules, watch how they work ....Single Molecule Studies of Replisomal Function. It has recently become possible to watch the copying of DNA molecules with a specialized microscope in real time. This process requires assembly of a complex molecular machine on the DNA, followed by triggering of its function, and yields exquisitely detailed information about how the machine works. In this new collaboration between scientists in Australia and the U.S.A., we will assemble these machines on single DNA molecules, watch how they work and simultaneously measure the very small forces that the machines generate. This will give Australian scientists access to a new technology for studying molecular machines.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100087
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
Regional Facility for Molecular Characterisation and Mapping. Researchers at the Schools of Chemistry at The Australian National University and University of Wollongong are involved in a range of projects where new molecules are synthesised or discovered in natural products such as rainforest plants and marine organisms. Some of the molecules have already shown promise against diseases such as Alzheimer's and cardiovascular disease. In order to fully characterise these molecules, two complementa ....Regional Facility for Molecular Characterisation and Mapping. Researchers at the Schools of Chemistry at The Australian National University and University of Wollongong are involved in a range of projects where new molecules are synthesised or discovered in natural products such as rainforest plants and marine organisms. Some of the molecules have already shown promise against diseases such as Alzheimer's and cardiovascular disease. In order to fully characterise these molecules, two complementary mass spectrometers, replacing ageing instrumentation will be commissioned at each site. In addition, researchers in Wollongong will acquire a MALDI mass spectrometer capable of imaging the distribution of molecules on tissues that may be pathologically important.Read moreRead less
Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several labora ....Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several laboratories in Australia and overseas to develop new understanding of how the molecular machine that copies DNA works. This k nowledge could lead to new drugs, and will give us new information about how cellular machines function.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0346876
Funder
Australian Research Council
Funding Amount
$1,584,000.00
Summary
800 MHz NMR Spectrometer for Molecular Structure-Function Analyses. An 800 MHz high-resolution nuclear magnetic resonance (NMR) spectrometer equipped with a triple-resonance cryoprobe is required to support the research of 5 universities in the NSW/ACT area. The high magnetic field of the spectrometer is necessary for the study of proteins, protein-ligand complexes and other biomolecular systems of molecular weight >30,000. Projects previously inaccessible due to sensitivity, solubility or resol ....800 MHz NMR Spectrometer for Molecular Structure-Function Analyses. An 800 MHz high-resolution nuclear magnetic resonance (NMR) spectrometer equipped with a triple-resonance cryoprobe is required to support the research of 5 universities in the NSW/ACT area. The high magnetic field of the spectrometer is necessary for the study of proteins, protein-ligand complexes and other biomolecular systems of molecular weight >30,000. Projects previously inaccessible due to sensitivity, solubility or resolution problems will become tractable. The increased turn-around times afforded by the high sensitivity of the cryo-enabled spectrometer make it possible to provide access for Australian institutions that would not otherwise have access to comparable equipment.Read moreRead less
Detecting stress-induced changes to subcellular copper pools in brain cells. Copper (Cu) plays essential roles in the functioning of brain cells, but the regulation and activity of this metal is poorly understood. This project aims to map sub-cellular Cu pools in brain cells, with particular emphasis on the effects of cellular stresses on these pools. These studies are expected to contribute important new methods for the study of Cu biology, and could provide valuable information about how Cu ho ....Detecting stress-induced changes to subcellular copper pools in brain cells. Copper (Cu) plays essential roles in the functioning of brain cells, but the regulation and activity of this metal is poorly understood. This project aims to map sub-cellular Cu pools in brain cells, with particular emphasis on the effects of cellular stresses on these pools. These studies are expected to contribute important new methods for the study of Cu biology, and could provide valuable information about how Cu homeostasis is maintained or perturbed under various stresses. In the future, this work is expected to form the basis of studies of brain Cu pools in neurodegenerative diseases.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100027
Funder
Australian Research Council
Funding Amount
$320,000.00
Summary
Sensitive and multinuclear: a dedicated facility for high-throughput characterisation of small molecules. This project will provide new cutting edge nuclear magnetic resonance equipment will enhance an existing shared analysis facility based at University of New South Wales. The new equipment will underpin research in polymers, neuropharmacology, the biological basis of inherited disease, nanomedicine, bioactive compounds and toxins.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100026
Funder
Australian Research Council
Funding Amount
$178,839.00
Summary
Ultrafast magic angle spinning solid-state nuclear magnetic resonance capability. This project aims to extend an existing nuclear magnetic resonance (NMR) spectrometer for structural investigations of proteins in the solid state. Many proteins, such as amyloids and flexible proteins, cannot be studied by X-ray crystallography, solution NMR spectroscopy or cryoelectron microscopy, because they cannot be crystallised or are not sufficiently soluble, or are structurally too heterogeneous. This proj ....Ultrafast magic angle spinning solid-state nuclear magnetic resonance capability. This project aims to extend an existing nuclear magnetic resonance (NMR) spectrometer for structural investigations of proteins in the solid state. Many proteins, such as amyloids and flexible proteins, cannot be studied by X-ray crystallography, solution NMR spectroscopy or cryoelectron microscopy, because they cannot be crystallised or are not sufficiently soluble, or are structurally too heterogeneous. This project will extend the capability of an existing 800 MHz NMR spectrometer to solid-state NMR. By offering ultrafast magic angle spinning speeds, the system aims to afford greatly enhanced sensitivity and multidimensional NMR spectra of protein systems not previously amenable to structural analysis by NMR spectroscopy or other techniques. This will have important applications in biotechnology and biomedicine.Read moreRead less