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
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
Protein structure controls light harvesting in photosynthetic light algae. The strange phenomena of quantum mechanics were not expected to play a direct role in life, however, it appears that quantum effects may be important in the efficient capture of sunlight for photosynthesis. The conditions for the emergence of quantum phenomena appear to be set by the structures of proteins. The aim of this project is to relate protein structure to the emergence of quantum effects in the light harvesting p ....Protein structure controls light harvesting in photosynthetic light algae. The strange phenomena of quantum mechanics were not expected to play a direct role in life, however, it appears that quantum effects may be important in the efficient capture of sunlight for photosynthesis. The conditions for the emergence of quantum phenomena appear to be set by the structures of proteins. The aim of this project is to relate protein structure to the emergence of quantum effects in the light harvesting proteins of marine algae. Understanding the link between structure and quantum effects could improve our knowledge of how nature achieves its remarkable efficiency in utilising the energy from the sun. This is likely to foster new technologies that improve the efficiency of solar energy systems.Read moreRead less
Flick the biological quantum switch: light controls photosynthetic proteins. This project aims to determine whether light conditions dictate which proteins, and hence quantum properties, a marine alga selects. The protein structures determine whether non-trivial quantum effects are available to the alga. Expected outcomes include fostering new technologies which will provide significant benefits, such as improving the efficiency of solar energy systems.
Structural and functional chacterisation of Acot7 in macrophages and its role in inflammation. This project will develop better understanding of the cellular pathways that mediate inflammation and will provide detailed information on a specific enzyme that produces arachidonic acid, the precursor to many inflammatory molecules, and characterisation of novel inhibitory binding sites.
Structural studies on chaperone protein machines from an Antarctic archeon. This project is to understand two fundamental biological processes, protein folding and prevention of RNA folding, that are crucial to all life, in particular, to survival in the cold. The project will determine the structure of the protein folding machine, showing how it works, and determine how RNA is protected after synthesis.
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
Discovery Early Career Researcher Award - Grant ID: DE160100608
Funder
Australian Research Council
Funding Amount
$359,000.00
Summary
Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibod ....Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibodies resistant to aggregation. Preliminary data indicates that stabilising mutations improves the biophysical properties of monoclonals without affecting the native antibody structure. The project aims to provide detailed insights into the molecular basis of antibody stability.Read moreRead less
Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolu ....Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolution crystal structures are being used to identify function. Intriguingly, preliminary data indicates that the mutations do not affect the native antibody structure, but rather influence dynamic states. The project plans to use a combination of mutagenesis, molecular dynamics simulation and deuterium exchange to study antibody dynamics.Read moreRead less