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
Complexity in a mesoscopic model of brain dynamics. Research into how the brain work remains at the frontier of human knowledge. We possess only the vaguest idea how the brain is able to generate memories, perceptions and behaviour. This research proposal concerns new approaches aimed at bridging this gap in our understanding by developing and studying detailed theories of the brain's electrical activity. The outcomes of this work will not only suggest improved diagnostic methods and treatments ....Complexity in a mesoscopic model of brain dynamics. Research into how the brain work remains at the frontier of human knowledge. We possess only the vaguest idea how the brain is able to generate memories, perceptions and behaviour. This research proposal concerns new approaches aimed at bridging this gap in our understanding by developing and studying detailed theories of the brain's electrical activity. The outcomes of this work will not only suggest improved diagnostic methods and treatments but contribute vital knowledge about how to control and predict the behaviour of complex systems.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883032
Funder
Australian Research Council
Funding Amount
$1,300,000.00
Summary
800 MHz NMR spectrometer for biomolecular structure-function analysis. An understanding of how organisms function at the molecular level is central to developing the ability to fight many diseases in a rational way. This equipment will provide the capability for many different laboratories around NSW and the ACT to advance our knowledge at this fundamental level, primarily by examining the structures and functions of biomolecules such as proteins.
Verification of a theoretical model of the dynamical genesis of brain electrical activity. The physiological basis for the rhythmic scalp electrical activity known as the alpha rhythm has remained elusive despite being first recorded over eighty years ago. However, one of the applicants (DTJL) has developed a novel theory of the electroencephalogram (EEG) that theoretically articulates the necessary physiological conditions required for the genesis of this activity that is subject to rigorous e ....Verification of a theoretical model of the dynamical genesis of brain electrical activity. The physiological basis for the rhythmic scalp electrical activity known as the alpha rhythm has remained elusive despite being first recorded over eighty years ago. However, one of the applicants (DTJL) has developed a novel theory of the electroencephalogram (EEG) that theoretically articulates the necessary physiological conditions required for the genesis of this activity that is subject to rigorous experimental test. Empirical verification of this theory will pave the way to elucidating the functional importance of large scale brain electrical activity in neural information processing as well as enabling the rational use of the EEG for drug design and diagnosis.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
Studying cell mechanics with a biophotonics-based tool. This study will help to promote and maintain good health. There is a connection between diseases such as arthritis and osteoporosis and cell mechanics. Our study will provide insight into cell mechanics, thereby helping to understand the pathophysiology of these diseases. The study is relevant to tissue engineering. There is ongoing research on mechanical conditioning of tissue substitutes. Understanding cell mechanics will help to optimise ....Studying cell mechanics with a biophotonics-based tool. This study will help to promote and maintain good health. There is a connection between diseases such as arthritis and osteoporosis and cell mechanics. Our study will provide insight into cell mechanics, thereby helping to understand the pathophysiology of these diseases. The study is relevant to tissue engineering. There is ongoing research on mechanical conditioning of tissue substitutes. Understanding cell mechanics will help to optimise conditioning protocols, thereby improving the properties of engineered tissue.
During this study we will develop optical tools that have applications in the life sciences, in the development of advanced materials and in nanotechnology. Our project will promote Australian research in these fields.Read moreRead less
Theoretical Studies on the KcsA Potassium Channel and the L-type Calcium Channel. All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms is a fundamental problem in biology. The project is aimed at developing a theoretical model of two important types of ion channels. Using a supercomputer, we will first deduce the shape of the microstructure formed by a protein wall. Then, using a computer simulation technique, we will c ....Theoretical Studies on the KcsA Potassium Channel and the L-type Calcium Channel. All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms is a fundamental problem in biology. The project is aimed at developing a theoretical model of two important types of ion channels. Using a supercomputer, we will first deduce the shape of the microstructure formed by a protein wall. Then, using a computer simulation technique, we will construct a set of physical models of biological ion channels, which will correctly replicate experimental observations. Such a theory will link the structure and function of an ion channel through the fundamental principles of physics.Read moreRead less