Ultrahigh resolution crystallography and ultrafast laser spectroscopy to uncover the evolution and mechanisms of a unique algal light harvesting system. The results of our research will provide the first comprehensive understanding of a biological light harvesting system at high temporal, energetic and spatial resolution. This will allow us to understand how nature has evolved highly efficient strategies for trapping light. The benefits of this work include spawning ideas as to how to improve ....Ultrahigh resolution crystallography and ultrafast laser spectroscopy to uncover the evolution and mechanisms of a unique algal light harvesting system. The results of our research will provide the first comprehensive understanding of a biological light harvesting system at high temporal, energetic and spatial resolution. This will allow us to understand how nature has evolved highly efficient strategies for trapping light. The benefits of this work include spawning ideas as to how to improve current technologies for enhancing optoelectronic devices and solar collectors. Protein systems are by nature nanotechnology. The understanding gained through probing a natural nanosystem will enhance our understanding of how human designed nanophotonic systems will behave. Read moreRead less
Functional Dissection of the Bacterial Replisome. We now have the complete sequences of genes in humans and many other organisms, but we know much less about how the protein products of the genes communicate with each other to create and grow cells. Australia has recently invested heavily in state-of-the-art instruments that can be used to tackle these problems. This project will involve close interaction of four laboratories to use new instruments to determine how a large assembly of proteins i ....Functional Dissection of the Bacterial Replisome. We now have the complete sequences of genes in humans and many other organisms, but we know much less about how the protein products of the genes communicate with each other to create and grow cells. Australia has recently invested heavily in state-of-the-art instruments that can be used to tackle these problems. This project will involve close interaction of four laboratories to use new instruments to determine how a large assembly of proteins interact in a biological machine that makes DNA. This process occurs in similar ways in all organisms, and is essential for life. Understanding how DNA is made will help scientists to develop new antibacterial drugs, and learn how to make practical use of molecular machines that imitate biology.Read moreRead less
THE BIOLOGY OF COLD ADAPTED EXTREMOPHILES: AN INTEGRATED GENOMIC-PROTEIN ANALYSIS APPROACH. Extremophiles are microorganisms that can thrive in otherwise inhospitable environments. Most extremophiles are Archaea; an order of life separate from Bacteria and Eucaryotes. The project will generate the first genome sequence that was initiated in Australia, and the first genome sequence of any cold adapted organism. Associated functional studies include global analyses of protein expression (proteo ....THE BIOLOGY OF COLD ADAPTED EXTREMOPHILES: AN INTEGRATED GENOMIC-PROTEIN ANALYSIS APPROACH. Extremophiles are microorganisms that can thrive in otherwise inhospitable environments. Most extremophiles are Archaea; an order of life separate from Bacteria and Eucaryotes. The project will generate the first genome sequence that was initiated in Australia, and the first genome sequence of any cold adapted organism. Associated functional studies include global analyses of protein expression (proteomics) and mRNA expression using micro-arrays, and work targeted at RNA binding proteins and protein folding systems involved in the thermally sensitive process of protein synthesis. The nature and scope of the work will impact on fundamental cellular processes and provide enormous innovative biotechnological potential.Read moreRead less
Nuclear magnetic resonance (NMR) studies of complex cellular responses: isotopomer sub-spaces, 'lost' ATP and 'tunable' anisotropy. Red blood cells (RBCs) transport oxygen around the body but they have other roles that are mediated by complex interconnecting metabolic pathways that generate myriad metabolites including ATP. A longstanding conundrum is the inability to account for ~60% of ATP turnover in human RBCs. Processes that may consume this 'lost' ATP, include autonomous motion of the cel ....Nuclear magnetic resonance (NMR) studies of complex cellular responses: isotopomer sub-spaces, 'lost' ATP and 'tunable' anisotropy. Red blood cells (RBCs) transport oxygen around the body but they have other roles that are mediated by complex interconnecting metabolic pathways that generate myriad metabolites including ATP. A longstanding conundrum is the inability to account for ~60% of ATP turnover in human RBCs. Processes that may consume this 'lost' ATP, include autonomous motion of the cell membrane called 'flickering', and maintenance of the biconcave-disc shape. NMR spectroscopy of quadrupolar nuclei in chiral aligned media, and isotopomer analysis will be used to define the kinetics of metabolism and membrane processes and thus help define the molecular basis of major blood disorders. Read moreRead less
NMR Spectroscopy of Complex Cellular Processes. The Theme is the cell viewed as a complex regulated molecular assembly. The Aim is to establish an integrated mathematical model of red cell metabolism, membrane transport, shape, and mechanical properties, principally by using NMR spectroscopy. The Significance will be discovery of new aspects of cellular structure and function, and new NMR theory for molecular bioscience. Outcomes will include new NMR measurements of kinetics of metabolic reactio ....NMR Spectroscopy of Complex Cellular Processes. The Theme is the cell viewed as a complex regulated molecular assembly. The Aim is to establish an integrated mathematical model of red cell metabolism, membrane transport, shape, and mechanical properties, principally by using NMR spectroscopy. The Significance will be discovery of new aspects of cellular structure and function, and new NMR theory for molecular bioscience. Outcomes will include new NMR measurements of kinetics of metabolic reactions, rates of membrane transport, solute diffusion, and functions of key membrane- and cytoskeletal proteins. Practical applications will include strategies for modelling complex biochemical systems, and circumventing metabolic defects arising from inheritance, the environment, and therapies.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
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882855
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
High-resolution imaging of live cells and tissue. Understanding the machinery of life and developing technologies that support life's processes requires biological and physical scientists and engineers to monitor molecular events in living systems. The aim is to take advantage of very recent developments in light microscopy to enable the non-invasive imaging of live cells and tissue at a previously unreachable level of detail. The instruments will form the nucleus of a new imaging facility. Sign ....High-resolution imaging of live cells and tissue. Understanding the machinery of life and developing technologies that support life's processes requires biological and physical scientists and engineers to monitor molecular events in living systems. The aim is to take advantage of very recent developments in light microscopy to enable the non-invasive imaging of live cells and tissue at a previously unreachable level of detail. The instruments will form the nucleus of a new imaging facility. Significant advances in research areas including vascular research, cancer, immunology, cell and molecular biology, functional genomics, biotechnology, nanotechnology and material engineering will be of major benefit both nationally and globally.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
Studies of the Dynamic Language of Bio-Molecular Communication and Signalling. For normal biological function, a multitude of external signals must be interpreted and responded to by cells. The responses must be carefully regulated and coordinated, or else pathological conditions will develop and, if not corrected, lead to uncontrolled proliferation or cell death. This project studies the mechanisms by which cells transmit signals. Proteins accomplish this communication by modifying the inter ....Studies of the Dynamic Language of Bio-Molecular Communication and Signalling. For normal biological function, a multitude of external signals must be interpreted and responded to by cells. The responses must be carefully regulated and coordinated, or else pathological conditions will develop and, if not corrected, lead to uncontrolled proliferation or cell death. This project studies the mechanisms by which cells transmit signals. Proteins accomplish this communication by modifying the interactions among their functional domains, effectively creating a conformational language. Knowledge of this language will impact biomedicine through its contributions to understanding the molecular pathology of diseased states, and biotechnology by enhancing our ability to use biological processes for applications.Read moreRead less