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Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are c ....Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are controlled, which is vital for developing better treatments for neurological disorders such as stroke. The project will also provide research training in experimental/computational molecular biology, which is a rapidly growing field underpinning the biotechnological and pharmaceutical industries. Read moreRead less
Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operati ....Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operation and seeking cures for diseases caused by their malfunction. This project aims to develop accurate ion-protein-water interactions for permeation models based on stochastic and molecular dynamics simulations using both classical and quantum mechanical methods.Read moreRead less
Quantum mechanical and dynamical investigation of ion channels. Many genetic diseases result from mutations in the genes that transcribe the channel proteins. Ion channels are also primary targets for development of therapeutic drugs for many ailments. Development of proper simulation tools is essential for a molecular-level understanding of their operation, which will be very helpful in finding treatments for genetic diseases as well as new drugs that target ion channels. Another aim of the p ....Quantum mechanical and dynamical investigation of ion channels. Many genetic diseases result from mutations in the genes that transcribe the channel proteins. Ion channels are also primary targets for development of therapeutic drugs for many ailments. Development of proper simulation tools is essential for a molecular-level understanding of their operation, which will be very helpful in finding treatments for genetic diseases as well as new drugs that target ion channels. Another aim of the project is to provide research training in computational biology. Research in this area is rapidly growing elsewhere but it has been rather neglected in Australia, and there is a shortage of researchers with such skills at present.Read moreRead less
Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales ....Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales with molecular dynamics at small distances and shorter times. Applications to both membrane proteins (blocking of ion channels by toxins and drugs) and globular proteins (ligand binding to receptors and protein association) will be considered.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
Matched experimental observation and finite-element simulation of flow-induced oscillations in uniform and tapered-stiffness collapsible tubes. Flexible tubes that can be flattened are widespread in the body and can act to limit flow-rate. Limitation is usually associated with spontaneous oscillation (repetitive opening and closing). There are many candidate explanations, but none has been shown to correspond with a given experiment. Through computer models and matched experiments on this couple ....Matched experimental observation and finite-element simulation of flow-induced oscillations in uniform and tapered-stiffness collapsible tubes. Flexible tubes that can be flattened are widespread in the body and can act to limit flow-rate. Limitation is usually associated with spontaneous oscillation (repetitive opening and closing). There are many candidate explanations, but none has been shown to correspond with a given experiment. Through computer models and matched experiments on this coupled system (the fluid flow interacts with the tube shape), we seek to demonstrate for the first time that a given theory/computer model encompasses the physics controlling a given observed oscillation. The solution will find application in other flexible-structure design problems in engineering, and also potentially in medicine.Read moreRead less
Matched experiments and numerical simulations of flow-induced oscillations in uniform and tapered-stiffness collapsible tubes. Flexible tubes that can be flattened are widespread in the body and can act to limit flow-rate. Limitation is usually associated with spontaneous oscillation (repetitive opening and closing). There are many candidate explanations, but none has been shown to correspond with a given experiment. Through computer models and matched experiments on this coupled system (the ....Matched experiments and numerical simulations of flow-induced oscillations in uniform and tapered-stiffness collapsible tubes. Flexible tubes that can be flattened are widespread in the body and can act to limit flow-rate. Limitation is usually associated with spontaneous oscillation (repetitive opening and closing). There are many candidate explanations, but none has been shown to correspond with a given experiment. Through computer models and matched experiments on this coupled system (the fluid flow interacts with the tube shape), we seek to demonstrate for the first time that a given theory/computer model encompasses the physics controlling a given observed oscillation. The solution will find application in other flexible-structure design problems in engineering, and also potentially in medicine.Read moreRead less
Synchrotrons, wavelet analysis and novel imaging techniques - applying physics tools to the war against breast cancer. Breast cancer leads to the second highest number of person-years of life lost due to cancer in Australia, with little known about its transport around the body. Current screening methods for breast cancer are neither 100% sensitive or specific and are heavily dependent upon expert training. This project will contribute by yielding valuable information on the transport of breast ....Synchrotrons, wavelet analysis and novel imaging techniques - applying physics tools to the war against breast cancer. Breast cancer leads to the second highest number of person-years of life lost due to cancer in Australia, with little known about its transport around the body. Current screening methods for breast cancer are neither 100% sensitive or specific and are heavily dependent upon expert training. This project will contribute by yielding valuable information on the transport of breast cancer and contribute to the development of an automated diagnostic method, with the possibility of its application to other diseases. The project will also involve members of the regional community, train regional scientists and provide synchrotron experience for Australian scientists in time for Australia's first synchrotron.Read moreRead less
Flow-induced oscillation in flexible tubes: experimental and numerical investigation of mechanism and onset. We seek to understand when instability arises in flow over very deformable structures. This will help us to design highly flexible structures specifically either to avoid the danger of flow-induced oscillations, which may be damaging (cardiac surgery, sails, parachutes), or in other circumstances to take advantage of them as an innovative way involving no sliding-parts mechanisms to crea ....Flow-induced oscillation in flexible tubes: experimental and numerical investigation of mechanism and onset. We seek to understand when instability arises in flow over very deformable structures. This will help us to design highly flexible structures specifically either to avoid the danger of flow-induced oscillations, which may be damaging (cardiac surgery, sails, parachutes), or in other circumstances to take advantage of them as an innovative way involving no sliding-parts mechanisms to create vibration, or flow pulsation, or sound, or motion (as in swimming-pool cleaners). Confidence in designing with highly flexible tubes will allow minimal resource consumption in manufacture of products to transport fluids, and will allow design use of the flow limitation property, whereby such a tube can control flow-rate.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0228799
Funder
Australian Research Council
Funding Amount
$1,602,000.00
Summary
Australian Membership of the International Gemini Partnership. The International Gemini Partnership is an intergovernmental consortium formed to construct and operate two 8-metre optical/infrared telescopes, one in Chile, and the other in Hawaii. Australia joined the IGP in May 1998, taking approximately 5% of the partnership. The Gemini telescopes have been carefully engineered to exploit the superb atmospheric conditions at both sites, allowing users to address key astronomical problems in way ....Australian Membership of the International Gemini Partnership. The International Gemini Partnership is an intergovernmental consortium formed to construct and operate two 8-metre optical/infrared telescopes, one in Chile, and the other in Hawaii. Australia joined the IGP in May 1998, taking approximately 5% of the partnership. The Gemini telescopes have been carefully engineered to exploit the superb atmospheric conditions at both sites, allowing users to address key astronomical problems in ways not previously possible. Through membership of Gemini, Australian astronomers have access to the world-class facilities necessary to maintain their high international profile and great public visibility in Galactic and extragalactic astronomy, and also to enhance the national capacity to construct advanced scientific instrumentation. Australia has already won a contract to build one of the instruments.Read moreRead less