Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. ....Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. Knowledge about this new aspect of protein degradation could provide a powerful tool to test the effect of the stabilisation or removal of specific proteins in the cell and also to develop new technologies in protein production.Read moreRead less
Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum- ....Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum-chemical methods and then test predictions experimentally. We will capitalise on our previous successful studies of Rubisco by addressing emergent issues which are the keys to understanding catalytic efficiency and CO2/O2 selectivity: the roles of a carbamylated lysine; the way CO2 addition is rendered irreversible; and the spin inversion inherent in O2 addition.Read moreRead less
Enabling Technologies for Structural Genomics. New technologies will be developed to save time, money and effort in rapid preparation of protein samples for structural genomics. Systems will be devised for preparing sufficient isotope-labelled proteins for nuclear magnetic resonance spectroscopy without using living organisms, for efficiently identifying points at which proteins can be broken into smaller fragments with the right properties, and for joining the ends of proteins and peptides toge ....Enabling Technologies for Structural Genomics. New technologies will be developed to save time, money and effort in rapid preparation of protein samples for structural genomics. Systems will be devised for preparing sufficient isotope-labelled proteins for nuclear magnetic resonance spectroscopy without using living organisms, for efficiently identifying points at which proteins can be broken into smaller fragments with the right properties, and for joining the ends of proteins and peptides together to make them much more stable. This combination of technologies are widely applicable to current problems in protein chemistry, molecular biology, functional genomics and the medical sciences.Read moreRead less
Predicting cell wall mechanics from structure in a materials engineering approach to plant growth. The project fosters a novel, interdisciplinary approach to understanding how the structure of plant cell walls determines their mechanical properties. Such understanding requires combining biological and engineering approaches and will illuminate how plants grow and produce cells and organs with particular shapes. This is scientifically important but is also important for industries depending on sp ....Predicting cell wall mechanics from structure in a materials engineering approach to plant growth. The project fosters a novel, interdisciplinary approach to understanding how the structure of plant cell walls determines their mechanical properties. Such understanding requires combining biological and engineering approaches and will illuminate how plants grow and produce cells and organs with particular shapes. This is scientifically important but is also important for industries depending on specialised cell shapes such as those of cotton and wood fibres. Our work will improve our understanding of how wall structure determines fibre and other cell shapes and give us tools which can be used to understand how final wall structure determines the fibre mechanics on which industrial users depend. Read moreRead less
New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein i ....New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein interaction sites and characterization of protein motions. The limits of NMR spectroscopy will be pushed to analyse systems of significantly increased molecular weights. The project includes applications to drug targets such as the dengue virus NS2B/NS3 protease.Read moreRead less
New Methods for Structural Biology in Solution. New technologies will be developed that are sufficiently rapid and inexpensive to compete with and replace the mutagenesis experiments that biologists usually perform to identify and characterize the functionally important parts of a protein. Nuclear magnetic resonance (NMR) spectroscopy techniques in combination with various selective labelling schemes will be developed with the goal of identification and structural characterization of protein-lig ....New Methods for Structural Biology in Solution. New technologies will be developed that are sufficiently rapid and inexpensive to compete with and replace the mutagenesis experiments that biologists usually perform to identify and characterize the functionally important parts of a protein. Nuclear magnetic resonance (NMR) spectroscopy techniques in combination with various selective labelling schemes will be developed with the goal of identification and structural characterization of protein-ligand interactions at increased rates and enhanced accuracy. In addition, the three-dimensional structures of proteins and protein domains of biologically important functions and unknown fold will be determined by NMR. The project aims at techniques of direct impact in pharmaceutical industry.Read moreRead less
Fluorine-labelled proteins for NMR spectroscopy. The technique developed in this project has direct impact on pharmaceutical research: NMR spectroscopy is used routinely to identify chemical compounds that bind to protein targets. This project includes the development of novel assignment techniques of 19F-labelled proteins, so that 19F-NMR can be used to detect specific binding interactions. One of the methods proposed here is designed to reveal structural information about the binding mode in s ....Fluorine-labelled proteins for NMR spectroscopy. The technique developed in this project has direct impact on pharmaceutical research: NMR spectroscopy is used routinely to identify chemical compounds that bind to protein targets. This project includes the development of novel assignment techniques of 19F-labelled proteins, so that 19F-NMR can be used to detect specific binding interactions. One of the methods proposed here is designed to reveal structural information about the binding mode in solution with atomic detail. This knowledge can significantly accelerate drug development. It is otherwise only available from crystal structures that can not always be determined.Read moreRead less
The Language of Knowledge. Knowledge is central to our lives. The way we attribute knowledge to others governs whom we trust, how we reason, what we do, and whether we succeed. The significance of this project consists in a deeper understanding of our attributions of knowledge, situated within the context of questions. This project offers the benefits of quality foundational research in an interdisciplinary venue. It connects to a range of areas of National Research Priority including An Environ ....The Language of Knowledge. Knowledge is central to our lives. The way we attribute knowledge to others governs whom we trust, how we reason, what we do, and whether we succeed. The significance of this project consists in a deeper understanding of our attributions of knowledge, situated within the context of questions. This project offers the benefits of quality foundational research in an interdisciplinary venue. It connects to a range of areas of National Research Priority including An Environmentally Sustainable Australia, Promoting and Managing Good Health, and Frontier Technologies for Building and Transforming Australian Industries, insofar as all of these areas of National Research Priority are concerned with the acquisition and transfer of knowledge.Read moreRead less
Perception, interpretation, and the explanation of delusional beliefs. The occurrence of bizarrely false beliefs, called delusions, presents challenges, not only for clinical psychiatric practice, but also for psychology, neuroscience, and philosophy. The aim of this project is to make a distinctively philosophical contribution to our understanding of delusional beliefs by addressing three philosophical questions raised by the study of delusions, questions about perception, interpretation, and e ....Perception, interpretation, and the explanation of delusional beliefs. The occurrence of bizarrely false beliefs, called delusions, presents challenges, not only for clinical psychiatric practice, but also for psychology, neuroscience, and philosophy. The aim of this project is to make a distinctively philosophical contribution to our understanding of delusional beliefs by addressing three philosophical questions raised by the study of delusions, questions about perception, interpretation, and explanation. Answers to these questions will constitute substantial contributions to three central areas of philosophy, but their significance also extends beyond philosophy. They will impact on the scientific investigation of delusions and will contribute indirectly to the treatment and rehabilitation of sufferers.
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Epistemic Warrant: Transmission Failure, Basic Knowledge, and Entitlement. This Project will bring substantial intellectual, cultural, and economic benefits to the nation - not only by increasing research strength, contributing to research output and establishing an international research partnership, but also by deepening the relationship between the study of the mind and theory of knowledge as a traditional area within philosophy and thus helping to maintain the pivotal position of philosophy ....Epistemic Warrant: Transmission Failure, Basic Knowledge, and Entitlement. This Project will bring substantial intellectual, cultural, and economic benefits to the nation - not only by increasing research strength, contributing to research output and establishing an international research partnership, but also by deepening the relationship between the study of the mind and theory of knowledge as a traditional area within philosophy and thus helping to maintain the pivotal position of philosophy in our intellectual life. Students, early-career researchers and established philosophers will benefit from access to the intellectual and institutional resources of international partner universities and there will be substantial and quantifiable financial contributions by international universities and research agencies.Read moreRead less