Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775708
Funder
Australian Research Council
Funding Amount
$289,680.00
Summary
X-ray Diffraction Microscope. The results of the research will substantially expand Australia's knowledge base in the area of diffraction, imaging and structural biology. It will build up our expertise in x-ray optics and synchrotron technology, and will open up a new approach to x-ray imaging and structure determination.
This will revolutionize our understanding of cellular and sub-cellular organisation with implications for the treatment of disease while the ability to determine structures ....X-ray Diffraction Microscope. The results of the research will substantially expand Australia's knowledge base in the area of diffraction, imaging and structural biology. It will build up our expertise in x-ray optics and synchrotron technology, and will open up a new approach to x-ray imaging and structure determination.
This will revolutionize our understanding of cellular and sub-cellular organisation with implications for the treatment of disease while the ability to determine structures of membrane proteins will open the door to fresh opportunities in rational drug design and biotechnology that will promote innovation in this industry, and the likely foundation of new start-up companies.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
Mapping Protein Contacts and Conformational Changes in Macromolecular Assemblies. We now have a great deal of information about the structures of proteins that interact to do much of the chemistry that governs the lives of cells and organisms, but are just beginning to understand how proteins communicate with each other in the large, dynamic molecular machines that carry out many cellular functions. Australia has invested in expensive instrumentation that can be used in conjunction with new labo ....Mapping Protein Contacts and Conformational Changes in Macromolecular Assemblies. We now have a great deal of information about the structures of proteins that interact to do much of the chemistry that governs the lives of cells and organisms, but are just beginning to understand how proteins communicate with each other in the large, dynamic molecular machines that carry out many cellular functions. Australia has invested in expensive instrumentation that can be used in conjunction with new laboratory methods to develop better understanding of how these machines work, and how they malfunction in disease. This project will bring together four scientists with a unique combination of expertise and novel technologies to develop understanding of changes in structure of a large protein complex in different functional states.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
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
Membrane interactions and neurotoxicity of Amyloid Abeta peptides from Alzheimer's disease. A consequence of the increase in human life span is that age-related neurodegenerative diseases such as Alzheimer's disease (AD) are more prevalent. Currently there are limited therapeutic treatments and no cure for AD. The key protein causing AD is Abeta and characterization of the toxic species of this peptide is critical towards identifying potential therapeutic targets. This proposal aims to study mut ....Membrane interactions and neurotoxicity of Amyloid Abeta peptides from Alzheimer's disease. A consequence of the increase in human life span is that age-related neurodegenerative diseases such as Alzheimer's disease (AD) are more prevalent. Currently there are limited therapeutic treatments and no cure for AD. The key protein causing AD is Abeta and characterization of the toxic species of this peptide is critical towards identifying potential therapeutic targets. This proposal aims to study mutant peptides made synthetically and to identify a membrane-binding site. By establishing which lipid is critically involved in membrane binding of Abeta and mediating subsequent cell death, drugs may be developed to prevent the binding of Abeta to membranes resulting in neuronal survival and prevention of memory loss in AD patients.Read moreRead less