DNA Dynamics is Shear and Extensional Flows: Simulation and Single Molecule Experiments. The proposal seeks to establish a collaboration between Monash University and Stanford University in order to combine several recent experimental and theoretical advances that have been made by the individual groups in single molecule experimental techniques, extensional rheometry, and molecular rheology, to obtain new insights into the structure and dynamics of biopolymers. The central aim is to make a sign ....DNA Dynamics is Shear and Extensional Flows: Simulation and Single Molecule Experiments. The proposal seeks to establish a collaboration between Monash University and Stanford University in order to combine several recent experimental and theoretical advances that have been made by the individual groups in single molecule experimental techniques, extensional rheometry, and molecular rheology, to obtain new insights into the structure and dynamics of biopolymers. The central aim is to make a significant contribution towards bringing state-of-the-art techniques used for the characterization of polymeric systems to bear on the nature and origin of the elastic properties of biopolymers.Read moreRead less
The flow properties of proteins and other biopolymers. The living cell is an extraordinary organization with a vast variety of biomacromolecules carrying out myriads of functions with great specificity and accuracy. The key issue in cell biology is to unravel the structures of biopolymers and the deep connection that exists between structure and function. This interdisciplinary research program combines recent advances in experimental and theoretical rheology, with advances in protein science, t ....The flow properties of proteins and other biopolymers. The living cell is an extraordinary organization with a vast variety of biomacromolecules carrying out myriads of functions with great specificity and accuracy. The key issue in cell biology is to unravel the structures of biopolymers and the deep connection that exists between structure and function. This interdisciplinary research program combines recent advances in experimental and theoretical rheology, with advances in protein science, to investigate the response of biopolymers to deformation. This approach will lead to insights into the problem of protein folding, the interaction of biopolymers with surfaces, and the physical basis for the mechanical properties of biopolymers.Read moreRead less
Fluorine-labelled proteins for NMR spectroscopy. The technique developed in this project has direct impact on pharmaceutical research: NMR spectroscopy is used routinely to identify chemical compounds that bind to protein targets. This project includes the development of novel assignment techniques of 19F-labelled proteins, so that 19F-NMR can be used to detect specific binding interactions. One of the methods proposed here is designed to reveal structural information about the binding mode in s ....Fluorine-labelled proteins for NMR spectroscopy. The technique developed in this project has direct impact on pharmaceutical research: NMR spectroscopy is used routinely to identify chemical compounds that bind to protein targets. This project includes the development of novel assignment techniques of 19F-labelled proteins, so that 19F-NMR can be used to detect specific binding interactions. One of the methods proposed here is designed to reveal structural information about the binding mode in solution with atomic detail. This knowledge can significantly accelerate drug development. It is otherwise only available from crystal structures that can not always be determined.Read moreRead less
TOWARDS A COMPLETE DESCRIPTION OF HOW ENZYMES WORK: development of simulation methods and protocols, blind test predictions, and experimental validation. Enzymes catalyze quite fantastic chemistry under mild physiological conditions. Many special chemical concepts (such as "transition-state stabilization" and "entropy-enthalpy compensation") proposed to explain these powers are unnecessary. Uniquely for a catalyst, these powers are integral to the structure, properties and dynamics of the protei ....TOWARDS A COMPLETE DESCRIPTION OF HOW ENZYMES WORK: development of simulation methods and protocols, blind test predictions, and experimental validation. Enzymes catalyze quite fantastic chemistry under mild physiological conditions. Many special chemical concepts (such as "transition-state stabilization" and "entropy-enthalpy compensation") proposed to explain these powers are unnecessary. Uniquely for a catalyst, these powers are integral to the structure, properties and dynamics of the protein, as constrained and selected by evolution. The question is how do they work? Answering this requires energetic and thermodynamic analysis beyond current experimental techniques, but accessible by computer simulation. We aim to develop a robust toolkit of simulation methods and protocols, blind test them by predicting the mechanism of a new enzyme, with followup experimental validation.
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Importance of conformational and electrostatic contributions in simulations of enzyme reaction mechanisms. The research will contribute to the development of biomolecular simulation in Australia by demonstrating its potential to complement experiment, and also promote the effective use of APAC (Australian national supercomputer facilities) resources by providing advanced programs and computational protocols for other researchers. It will assist the diffusion of computational biology technology i ....Importance of conformational and electrostatic contributions in simulations of enzyme reaction mechanisms. The research will contribute to the development of biomolecular simulation in Australia by demonstrating its potential to complement experiment, and also promote the effective use of APAC (Australian national supercomputer facilities) resources by providing advanced programs and computational protocols for other researchers. It will assist the diffusion of computational biology technology into industrial applications such as rational drug design and protein engineering, as, for example, in our associated Linkage project grant, and provide novel insights into protein engineering and other sorts of design, which transcend concepts currently used in biomimetic chemistry.Read moreRead less
Characterization and optimisation of Myomatrix: A novel extracellular matrix hydrogel from muscle. This project would have several sources of benefit for the community. Foremost we will have produced a product that will have a strong commercial application in several fields including basic science and bioengineering. If its full potential were achieved, the development of this innovative new hydrogel would strengthen Australia's standing in the biotechnology field and also enrich specific applic ....Characterization and optimisation of Myomatrix: A novel extracellular matrix hydrogel from muscle. This project would have several sources of benefit for the community. Foremost we will have produced a product that will have a strong commercial application in several fields including basic science and bioengineering. If its full potential were achieved, the development of this innovative new hydrogel would strengthen Australia's standing in the biotechnology field and also enrich specific applications. The knowledge gained from the characterization of this product could also be of benefit to several areas including chemical engineering, tissue engineering, tissue repair, polymer chemistry and food manufacture. The expertise generated and the possibility of collaboration, both academic and with industry would also benefit the community. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100010
Funder
Australian Research Council
Funding Amount
$720,000.00
Summary
A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the ....A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the nation's research priorities. It will enable: fundamental studies of cancer, neural diseases and immune disorders; the development of frontier technologies, such as smart nanomaterials, biosensors and targeted drug delivery; and applied research to help plants and soils adapt to climate variability, and to increase sustainable use of water.Read moreRead less