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
"Painting" the 3D proteome: folding, conformation and interactions. The project aims to develop a "residue painting approach", employing novel chemical biology reagents and advanced quantitative proteomics, to monitor changes in protein folding, conformations and interactions in cells, in response to stimuli. Proteins direct almost all functions required to sustain life. The project expects to map the dynamic 3D-structures of thousands of proteins that inform the networks they are in, and of the ...."Painting" the 3D proteome: folding, conformation and interactions. The project aims to develop a "residue painting approach", employing novel chemical biology reagents and advanced quantitative proteomics, to monitor changes in protein folding, conformations and interactions in cells, in response to stimuli. Proteins direct almost all functions required to sustain life. The project expects to map the dynamic 3D-structures of thousands of proteins that inform the networks they are in, and of the conformations they adopt. Expected outcomes include the development of novel biotechnology tools for protein structure and function analysis, the illumination of important cell biology pathways underpinning molecular responses to stimuli and stress, and the training of our next generation of scientists.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.
Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiolo ....Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiological stimuli to control electrical signalling the body. Our results will provide benefits in the form of basic understanding relevant to ion transport phenomena in biological systems, and atomic-level views of nervous system function to guide future directions in pharmacology.Read moreRead less
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