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
Shear stimulated Brillouin microscopy for cell mechanobiology. This project aims to develop novel technology for non-contact imaging of micro-mechanical properties in cells and tissues to answer fundamental questions of cell mechnanobiology. Based on principles of Brillouin light scattering, the project takes advantage of a radio-frequency lock-in detection scheme. The project will result in a real-time, high-sensitivity, non-contact 3D imaging solution for spatial characterisation of cell's loc ....Shear stimulated Brillouin microscopy for cell mechanobiology. This project aims to develop novel technology for non-contact imaging of micro-mechanical properties in cells and tissues to answer fundamental questions of cell mechnanobiology. Based on principles of Brillouin light scattering, the project takes advantage of a radio-frequency lock-in detection scheme. The project will result in a real-time, high-sensitivity, non-contact 3D imaging solution for spatial characterisation of cell's local stiffness and compressibility. This will underpin the advancement of knowledge in the area of cell mechanobiology and the investigation of diseases, where microscale changes in cell mechanical properties lead to cell dysfunction and apoptosis.Read moreRead less
Connecting the dots: Image analysis for single molecule localisation microscopy. It is now possible to record the positions of single fluorescent molecules in intact cells to build up an image literally molecule by molecule. But how to ‘connect the dots’ and extract structural information from molecular coordinates is yet to be worked out. The project aims to do exactly that, and write and implement novel analysis routines to quantify a diverse range of biological structures such as protein comp ....Connecting the dots: Image analysis for single molecule localisation microscopy. It is now possible to record the positions of single fluorescent molecules in intact cells to build up an image literally molecule by molecule. But how to ‘connect the dots’ and extract structural information from molecular coordinates is yet to be worked out. The project aims to do exactly that, and write and implement novel analysis routines to quantify a diverse range of biological structures such as protein complexes, membrane morphologies, filamentous cytoskeletal networks, vesicles and viruses. The project is a collaboration between a cell biologist (Professor Gaus) who is a leader in single molecule localisation microscopy, an expert in fluorescence image analysis (Dr Nicovich) and an industry partner (Dr Lucas) who has a sophisticated software platform.Read moreRead less
Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematic ....Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematical model of the regulation of cell-shape and volume. The project will provide an understanding of mechanisms operating when cells and tissues are succumbing to trauma and invasion, and how to control these processes on a molecular level.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100171
Funder
Australian Research Council
Funding Amount
$200,000.00
Summary
Shared resource for protein discovery. This facility will enable the production and characterisation of proteins from all kingdoms of life that have diverse roles in fundamental biology and disease. A detailed understanding of how these proteins behave and function will be used to generate therapeutics and develop novel applications for these proteins in medicine and industry.