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Elucidating the determinants of cation import across the kingdoms of life. The metal ion manganese is essential to all forms of life. This project aims to investigate how this poorly abundant cation is selectively acquired from the chemical complexity of the environment for import into cells by using state-of-the-art biochemical and microbiological techniques. This project expects to define the fundamental basis for how bacterial, archaeal and eukaryotic plastid cation-selective importers can di ....Elucidating the determinants of cation import across the kingdoms of life. The metal ion manganese is essential to all forms of life. This project aims to investigate how this poorly abundant cation is selectively acquired from the chemical complexity of the environment for import into cells by using state-of-the-art biochemical and microbiological techniques. This project expects to define the fundamental basis for how bacterial, archaeal and eukaryotic plastid cation-selective importers can discriminate manganese from chemical similar cations to achieve selective uptake. The expected outcomes of this work will be an understanding of the fundamental basis for selective metal import in biological systems. This should provide benefits for industry through synthetic biological applications of this knowledge. Read moreRead less
Molecular mechanisms for copper trafficking across membranes. Copper is a trace metal that is essential for all forms of life, however it is toxic in excess. Tightly controlled protein-based metalloregulatory systems are responsible for copper uptake and homeostasis in all cells. Components of these systems are integral membrane transport proteins, which include the Ctr proteins that are solely responsible for copper uptake into eukaryotic cells. This project aims to define the molecular mechani ....Molecular mechanisms for copper trafficking across membranes. Copper is a trace metal that is essential for all forms of life, however it is toxic in excess. Tightly controlled protein-based metalloregulatory systems are responsible for copper uptake and homeostasis in all cells. Components of these systems are integral membrane transport proteins, which include the Ctr proteins that are solely responsible for copper uptake into eukaryotic cells. This project aims to define the molecular mechanisms by which the Ctr proteins transport copper across eukaryotic cell membranes, by solving their three-dimensional structures by X-ray crystallography.Read moreRead less
Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected ....Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected to help guide the development of new agents for selectively delivering imaging and biologically active agents to cells.Read moreRead less
Characterising the transport and delivery of oligonucleotides . Short RNA and DNA molecules represent a class of macromolecules that have great potential, but to facilitate their trafficking across cellular and membrane barriers into specific sites of action is challenging. This project aims to develop and apply novel imaging approaches to track them in cells and tissues. Expected outcomes include better understanding of the trafficking across cellular and membrane barriers, and improved imaging ....Characterising the transport and delivery of oligonucleotides . Short RNA and DNA molecules represent a class of macromolecules that have great potential, but to facilitate their trafficking across cellular and membrane barriers into specific sites of action is challenging. This project aims to develop and apply novel imaging approaches to track them in cells and tissues. Expected outcomes include better understanding of the trafficking across cellular and membrane barriers, and improved imaging tools that could be used to further study the molecular mechanisms of accumulation, metabolism and trafficking of these molecules. This project should provide new strategies to target these molecules to specific cells and tissues, which have significant social and economic benefits to the Australian community.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC200100052
Funder
Australian Research Council
Funding Amount
$4,789,838.00
Summary
ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide signifi ....ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide significant benefits including advancing Australian biotechnological capacity and improved linkages with major pharmaceutical partners. It should also provide a substantive competitive advantage to nascent Australian biotechnology companies that also links into new National investment into drug discovery and development infrastructure.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150100784
Funder
Australian Research Council
Funding Amount
$373,254.00
Summary
Molecular probe development for the oxytocin and vasopressin receptors. The oxytocin and vasopressin receptors are part of a 600 million year old signalling system that is widely distributed in the kingdom of life. It is involved in many fundamental physiological functions, however we still lack a complete toolbox of selective probes to delineate the individual receptor subtypes. This project aims to introduce a novel and innovative strategy that uses state-of-the art discovery techniques to ide ....Molecular probe development for the oxytocin and vasopressin receptors. The oxytocin and vasopressin receptors are part of a 600 million year old signalling system that is widely distributed in the kingdom of life. It is involved in many fundamental physiological functions, however we still lack a complete toolbox of selective probes to delineate the individual receptor subtypes. This project aims to introduce a novel and innovative strategy that uses state-of-the art discovery techniques to identify selective ligands in nature. Leads will be developed into molecular probes to facilitate in-depth studies of this system. This strategy is applicable to other systems and the outcomes will contribute to a significant advancement of knowledge in chemical biology.Read moreRead less
Membrane proteins: understanding biological switches, motors and triggers. By extending the range of biomolecular systems that can be modelled computationally at the atomic level, this project will enable fundamental cellular processes such as how molecules are transported across cell membranes or how the binding of a hormone to an extracellular receptor sends a signal in a cell to be understood in unprecedented detail.
Understanding biological membranes in atomic detail. The aim of the project is to develop the capacity to represent specific mammalian, fungal and bacterial membranes in atomic detail and to use such models to understand the role of membrane composition in the structure and dynamics of membrane proteins at an atomic level. Membrane protein assemblies are the ultimate nanoscale machines. Understanding these sub-cellular components is both a fundamental theoretical challenge and of widespread prac ....Understanding biological membranes in atomic detail. The aim of the project is to develop the capacity to represent specific mammalian, fungal and bacterial membranes in atomic detail and to use such models to understand the role of membrane composition in the structure and dynamics of membrane proteins at an atomic level. Membrane protein assemblies are the ultimate nanoscale machines. Understanding these sub-cellular components is both a fundamental theoretical challenge and of widespread practical importance in biochemistry, structural biology and medicine. By representing in detail the complexity of biological membranes, the project aims to elucidate the role played by specific membrane components in determining the mechanism of action of proteins involved in transport and signal transduction in context.Read moreRead less
How cholesterol optimises ion pump function in animal membranes. This project aims to determine how cholesterol optimises ion pump function in animal membranes and to identify the major effects of cholesterol and its derivatives on membranes’ physical properties. All animal cells need high levels of cholesterol in the plasma membrane for survival. Insufficient cholesterol biosynthesis leads to severe birth defects. The need for cholesterol is likely linked to its acceleration of sodium pump acti ....How cholesterol optimises ion pump function in animal membranes. This project aims to determine how cholesterol optimises ion pump function in animal membranes and to identify the major effects of cholesterol and its derivatives on membranes’ physical properties. All animal cells need high levels of cholesterol in the plasma membrane for survival. Insufficient cholesterol biosynthesis leads to severe birth defects. The need for cholesterol is likely linked to its acceleration of sodium pump activity, essential to physiological processes including cell division, nerve, muscle and kidney activity. An expected benefit of the project is knowledge on the molecular origin of diseases associated with inhibition of cholesterol production, and a more complete understanding of the crucial role played by cholesterol via its effect on ion pumping towards the healthy functioning of vital organs, particularly in heart muscle and nerves.Read moreRead less
Lipid-protein interplay in the mechanism of the sodium pump. The sodium pump is the major energy-consuming enzyme of animal cells. Its ion pumping is essential to numerous physiological processes (e.g. nerve, muscle and kidney activity and the maintenance of cell volume). Because of its importance in so many cell functions, the enzyme must be able to respond to cellular conditions. Using measurements of the enzyme's activity in isolated membrane fragments and comparison with its behaviour in liv ....Lipid-protein interplay in the mechanism of the sodium pump. The sodium pump is the major energy-consuming enzyme of animal cells. Its ion pumping is essential to numerous physiological processes (e.g. nerve, muscle and kidney activity and the maintenance of cell volume). Because of its importance in so many cell functions, the enzyme must be able to respond to cellular conditions. Using measurements of the enzyme's activity in isolated membrane fragments and comparison with its behaviour in living cells, this project aims to determine how sodium pump activity is modulated by transmembrane electric potential and intramembrane electric field strength. Our project could provide fundamental new knowledge on how membrane protein function in general can be controlled by electrical properties of their lipid surroundings.Read moreRead less