Improved patient care and image resolution in magnetic resonance imaging. A better understanding of the vibration within MRIs would result in techniques to both improve the image resolution and lower the noise emissions. Direct improvement of health care for Australians will result. Both the patient and the working environment around these scanners will improve as well as image resolution. Presently imaging is possible at the cellular scale, but only through improved MRI stability will imaging r ....Improved patient care and image resolution in magnetic resonance imaging. A better understanding of the vibration within MRIs would result in techniques to both improve the image resolution and lower the noise emissions. Direct improvement of health care for Australians will result. Both the patient and the working environment around these scanners will improve as well as image resolution. Presently imaging is possible at the cellular scale, but only through improved MRI stability will imaging reach the molecular level. Medical research that is linked to MRI imaging can be expected to advance in step with improved image resolution. The resulting knowledge could also be used in other research and industrial areas, including micro- and nano-scale devices, where vibration is a critical performance limiting factor.Read moreRead less
Structural analysis of a novel plasma membrane coat complex. The plasma membrane of mammalian cells forms a crucial barrier between the cell and the outside world. This project investigates how a newly-discovered family of proteins work together to generate specialised regions of the plasma membrane called caveolae.
Structural basis for the assembly of caveolae. Caveolae are small invaginations of the plasma membrane and are a characteristic feature of eukaryotic cells. Described morphologically in the early 1950s their many important functions are only just beginning to be revealed. Caveolae are multifunctional organelles that play a vital role in normal cellular processes such as signalling and membrane homeostasis, and are perturbed in cancer, lipid storage and muscle diseases. A new family of coat prote ....Structural basis for the assembly of caveolae. Caveolae are small invaginations of the plasma membrane and are a characteristic feature of eukaryotic cells. Described morphologically in the early 1950s their many important functions are only just beginning to be revealed. Caveolae are multifunctional organelles that play a vital role in normal cellular processes such as signalling and membrane homeostasis, and are perturbed in cancer, lipid storage and muscle diseases. A new family of coat proteins called cavins have recently been discovered. Cavins are essential for the formation of caveolae, and this project seeks to understand how these multiprotein complexes are assembled at the membrane interface and control caveola function at the molecular level.Read moreRead less
How bacteria cause disease in the urinary tract. This project will investigate the virulence properties of uropathogenic Escherichia coli, the major causative agent of urinary tract infections (UTI) in humans. The results will help to understand how these bacterial pathogens cause disease and will impact strategies aimed at the prevention and treatment of chronic and recurrent UTI.
Mechanism of AMPK activation by drugs and metabolites. This project aims to identify the molecular basis of activation mechanisms in the AMP-activated protein kinase (AMPK), an enzyme that regulates burning and storage of fuels such as fat and sugars, autophagy and controls appetite and energy expenditure. This project expects to provide insights into how energy metabolism and physiological functions are linked.
Force Fields for Structure Refinement and Computational Drug Design. The ability to model molecular systems at an atomic level, as used in protein structure refinement or computational drug design, is critically dependent on the accuracy with which inter-atomic interactions are represented. Highly optimised and well-validated interaction parameters are available for common biomolecules, such as amino acids, sugars and lipids, but not for co-factors, substrates and potential drug molecules, or ot ....Force Fields for Structure Refinement and Computational Drug Design. The ability to model molecular systems at an atomic level, as used in protein structure refinement or computational drug design, is critically dependent on the accuracy with which inter-atomic interactions are represented. Highly optimised and well-validated interaction parameters are available for common biomolecules, such as amino acids, sugars and lipids, but not for co-factors, substrates and potential drug molecules, or other molecules of interest such as polymers and dendrimers. The aim of this project is to develop and validate geometric and interaction parameters (force fields) for complex organic molecules and use these to facilitate bio-molecular structure refinement and computational drug design.Read moreRead less
Improving empirical force fields: a big-data approach. This project aims to improve the ability to represent the thermodynamic properties of molecules of biological, pharmaceutical or materials interest by developing force fields capable of describing a diverse range of molecules both consistently and with high fidelity. The project aims to exploit a rapidly expanding, in-house database of parameterized molecular structures to develop highly optimised, well-validated parameters that are both con ....Improving empirical force fields: a big-data approach. This project aims to improve the ability to represent the thermodynamic properties of molecules of biological, pharmaceutical or materials interest by developing force fields capable of describing a diverse range of molecules both consistently and with high fidelity. The project aims to exploit a rapidly expanding, in-house database of parameterized molecular structures to develop highly optimised, well-validated parameters that are both consistent and transferable, enabling molecules of any size or complexity to be parameterised with a fidelity currently only possible for simple organics. This will provide significant benefits, such as helping to improve the accuracy and reliability of ligand: protein complexes determined experimentally, a limiting factor in computational drug design.Read moreRead less
Imaging-based fluid-structure interaction modelling of carotid atherosclerotic plaque. This project aims to combine computational modelling, magnetic resonance imaging (MRI), mechanical measurement and pathological analysis to investigate carotid plaque progression, and quantify the critical blood flow and plaque stress/strain conditions under which plaque rupture is likely to occur. MRI-based 3D computational models with multi-component plaque structures and their interaction with blood flow wi ....Imaging-based fluid-structure interaction modelling of carotid atherosclerotic plaque. This project aims to combine computational modelling, magnetic resonance imaging (MRI), mechanical measurement and pathological analysis to investigate carotid plaque progression, and quantify the critical blood flow and plaque stress/strain conditions under which plaque rupture is likely to occur. MRI-based 3D computational models with multi-component plaque structures and their interaction with blood flow will be developed and solved numerically to identify suitable plaque rupture risk indicators. Mechanical properties of plaque components will be measured ex-vivo and fibre orientation-based constitutive rules will be developed. This project aims to lead to quantitative understandings of plaque progression and rupture.Read moreRead less
How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. ....How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. This will have significant benefits, such as providing the basis for the development of approaches to block auto-transporter functions that contribute to the establishment of persistent and difficult to treat bacterial infections.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102857
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Innovative chemical tools for the isolation, biochemical and structural analysis of biological macromolecular assemblies. This project will develop a new approach for determining the three dimensional structures of protein complexes. This project will demonstrate this approach by determining the structure of a protein complex involved in gene regulation and disease.