New methods for structure analysis of proteins and protein interactions. This project will advance nuclear magnetic resonance (NMR) technologies pioneered at the Australian National University which employ site-specific attachment of paramagnetic metal tags to proteins. A new and diverse set of strategies will dramatically extend the range of applications to targets of interest in the fight against cancer and bacterial infections.
Australian Laureate Fellowships - Grant ID: FL170100019
Funder
Australian Research Council
Funding Amount
$2,606,250.00
Summary
Proteins in motion - new tools for biotechnology. This project aims to assess the function of proteins by monitoring their motions using new nuclear magnetic resonance (NMR) spectroscopy techniques. As snapshots of 3D protein structures have been determined by crystallography, the new tools are designed to analyse functionally important motions in solution. A facility for ultrafast (> 100 kHz) magic angle spinning NMR spectroscopy of proteins in the semi-solid state will bring cutting-edge know- ....Proteins in motion - new tools for biotechnology. This project aims to assess the function of proteins by monitoring their motions using new nuclear magnetic resonance (NMR) spectroscopy techniques. As snapshots of 3D protein structures have been determined by crystallography, the new tools are designed to analyse functionally important motions in solution. A facility for ultrafast (> 100 kHz) magic angle spinning NMR spectroscopy of proteins in the semi-solid state will bring cutting-edge know-how to Australia and allow the interrogation of 3D structure and dynamics in selected protein regions. The expected outcomes of the project will have immediate benefits for the rational engineering of biocatalysts and in the design of lead compounds in drug development.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100893
Funder
Australian Research Council
Funding Amount
$364,000.00
Summary
How do effector proteins from necrotrophic fungi cause disease in plants? This project aims to develop new knowledge to support the development of strategies to protect wheat from necrotrophic fungi. Crop losses caused by plant diseases are a significant economic, environmental and social challenge in a world facing increased demands on food, fibre and biofuels. Parastagonospora nodorum is an economically important necrotrophic fungal pathogen of wheat. During infection, P. nodorum uses effector ....How do effector proteins from necrotrophic fungi cause disease in plants? This project aims to develop new knowledge to support the development of strategies to protect wheat from necrotrophic fungi. Crop losses caused by plant diseases are a significant economic, environmental and social challenge in a world facing increased demands on food, fibre and biofuels. Parastagonospora nodorum is an economically important necrotrophic fungal pathogen of wheat. During infection, P. nodorum uses effector proteins to target sensitivity gene products in wheat. This process, known as necrotrophic effector-triggered susceptibility, results in plant cell death and disease. This project aims to investigate the structural basis of necrotrophic effector-triggered susceptibility in the P. nodorum – wheat pathosystem.Read moreRead less
Drug discovery and structural biology by NMR spectroscopy. This project aims to extend the use of nuclear magnetic resonance (NMR) spectroscopy in rational drug development and protein structure analysis. A new chemical labelling approach provides detailed three-dimensional structure information of large protein-ligand complexes, needed for structure-based lead-compound development. New chemical and paramagnetic lanthanide tags for site-specific dual labelling of proteins will enhance this techn ....Drug discovery and structural biology by NMR spectroscopy. This project aims to extend the use of nuclear magnetic resonance (NMR) spectroscopy in rational drug development and protein structure analysis. A new chemical labelling approach provides detailed three-dimensional structure information of large protein-ligand complexes, needed for structure-based lead-compound development. New chemical and paramagnetic lanthanide tags for site-specific dual labelling of proteins will enhance this technology, which will assess target-drug interactions by in-cell electron paramagnetic resonance (EPR) spectroscopy. The techniques offer scope for accelerated drug development in the pharmaceutical industries.Read moreRead less
New methods for structural biology and drug discovery by nuclear magnetic resonance spectroscopy. Paramagnetic lanthanide tags offer fresh opportunities in structural biology and for rational drug design. Novel nuclear magnetic resonance (NMR) spectroscopy techniques will selectively detect the NMR signals from protein regions marked by paramagnetic lanthanides, accelerating the structure analysis of protein-ligand complexes. New lanthanide tags will bind to phosphoserine and selenocysteine resi ....New methods for structural biology and drug discovery by nuclear magnetic resonance spectroscopy. Paramagnetic lanthanide tags offer fresh opportunities in structural biology and for rational drug design. Novel nuclear magnetic resonance (NMR) spectroscopy techniques will selectively detect the NMR signals from protein regions marked by paramagnetic lanthanides, accelerating the structure analysis of protein-ligand complexes. New lanthanide tags will bind to phosphoserine and selenocysteine residues site-specifically introduced into proteins. These tags will also enable accurate distance measurements by electron paramagnetic resonance (EPR) spectroscopy in large, biologically important protein systems hitherto not amenable to detailed structural studies and in proteins undergoing conformational changes. Read moreRead less
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
Force-from-lipids biophysical principle underlying mechanotransduction. The major aim of this project is to determine evolutionary conserved physical principles of mechanotransduction in living cells through structure and function studies of PIEZO mechanoreceptor channels playing a crucial role in senses such as touch and pain in animals and humans. Mutations in these channels can cause numerous genetic disorders, including hereditary anaemias and joint contractures. Since they have been shown t ....Force-from-lipids biophysical principle underlying mechanotransduction. The major aim of this project is to determine evolutionary conserved physical principles of mechanotransduction in living cells through structure and function studies of PIEZO mechanoreceptor channels playing a crucial role in senses such as touch and pain in animals and humans. Mutations in these channels can cause numerous genetic disorders, including hereditary anaemias and joint contractures. Since they have been shown to respond to mechanical stimuli in the same manner as mechanoreceptor channels of organisms from bacteria to humans the intended outcome of this project is to uncover the unifying principles of mechanotransduction anchored in the laws of physics and chemistry that have guided the force-dependent design of all life forms.Read moreRead less
Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins ....Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins of high biochemical or biomedical importance, and the approach will be applied to established drug targets.Read moreRead less
Protein design. This project aims to design binding specificity in proteins in a rational way. Extending the existing repertoire of protein specificity using engineering principles should harness the catalytic power and high binding affinities of natural proteins. By building upon protein design algorithms, this project will develop biosensors for neurotransmitters and specialist enzymes to incorporate unnatural amino acids. It will iteratively improve the designs and algorithms by computational ....Protein design. This project aims to design binding specificity in proteins in a rational way. Extending the existing repertoire of protein specificity using engineering principles should harness the catalytic power and high binding affinities of natural proteins. By building upon protein design algorithms, this project will develop biosensors for neurotransmitters and specialist enzymes to incorporate unnatural amino acids. It will iteratively improve the designs and algorithms by computational and experimental characterisation. The outcomes should address the long-standing need in synthetic biology for a facile route to designer proteinsRead moreRead less