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
Novel approaches for structural and functional analysis of the protein complex COG, a tether that controls intra-Golgi trafficking. Production and engineering of proteins are key methodologies of the life sciences in general and biotechnology in particular. Our ability to produce and analyse protein-based components of the cell determines the expense and speed of discovery, as well as the creation of new vaccines, drugs, and diagnostic methods. The current project aims to develop new approaches ....Novel approaches for structural and functional analysis of the protein complex COG, a tether that controls intra-Golgi trafficking. Production and engineering of proteins are key methodologies of the life sciences in general and biotechnology in particular. Our ability to produce and analyse protein-based components of the cell determines the expense and speed of discovery, as well as the creation of new vaccines, drugs, and diagnostic methods. The current project aims to develop new approaches for protein production and to apply them to the analysis of the basic mechanisms of cell self-maintenance.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100125
Funder
Australian Research Council
Funding Amount
$330,000.00
Summary
Oxidative stress bioanalytical facility. The primary national benefit of this application is that it will provide a currently unavailable, state-of-the-art facility for Australian scientists to define precisely how changes in cellular redox state contribute to biological processes relevant to health and diseases. The facility will uniquely complement, and in many cases integrate with existing facilities in this area of research in Australia. It will act as a platform for major national and inter ....Oxidative stress bioanalytical facility. The primary national benefit of this application is that it will provide a currently unavailable, state-of-the-art facility for Australian scientists to define precisely how changes in cellular redox state contribute to biological processes relevant to health and diseases. The facility will uniquely complement, and in many cases integrate with existing facilities in this area of research in Australia. It will act as a platform for major national and international research collaborations, develop cutting-edge technology and unique local skills, and contribute to Australia maintaining a leading position in redox-related research in biology and medicine. In doing so, the facility will increase the likelihood of gaining future, value-adding funding.Read moreRead less
The molecular mechanism of retromer and sorting nexin function in endosomal membrane trafficking. The proposed research represents breakthrough science that will lead to a fundamental understanding at the molecular level of the structure and assembly of the retromer complex and how it regulates sorting of receptors in the endosomal system. It will provide excellent research training for top graduate students and post-doctoral scientists in multidisciplinary methods that constitute state-of the- ....The molecular mechanism of retromer and sorting nexin function in endosomal membrane trafficking. The proposed research represents breakthrough science that will lead to a fundamental understanding at the molecular level of the structure and assembly of the retromer complex and how it regulates sorting of receptors in the endosomal system. It will provide excellent research training for top graduate students and post-doctoral scientists in multidisciplinary methods that constitute state-of the-art structural and molecular cell biology research. By addressing an area of great interest internationally the project will have the capacity to increase Australia's knowledge base and strengthen it's reputation for research excellence.Read moreRead less
Neurons isolated from embryonic stem cells as functional models for drug discovery. By using gene expression-based selection criteria embryonic stem cells can be driven to differentiate into specific neuronal lineages which show many of the morphological characteristics and immunocytochemical features of neurons in culture. There is, however, comparatively little evidence indicating that these stem cell-derived neurons actually behave as neurons. Our aim is to characterise and contrast four ne ....Neurons isolated from embryonic stem cells as functional models for drug discovery. By using gene expression-based selection criteria embryonic stem cells can be driven to differentiate into specific neuronal lineages which show many of the morphological characteristics and immunocytochemical features of neurons in culture. There is, however, comparatively little evidence indicating that these stem cell-derived neurons actually behave as neurons. Our aim is to characterise and contrast four neuronal cell cultures established with gene-based selection criteria. These cultures will be characterised by gene expression, immunocytochemistry, radiolabelled neurotransmitter release, electrophysiology and Ca2+ imaging studies. This study will highlight the functional effects of gene selection procedures upon stem cell-derived neurons.Read moreRead less
Endosomal Protein Transport: From Molecular Structures to Biological Function. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling, homoeostasis and development. Defects in this fundamental process and subversion of it by bacterial and viral pathogens also lead to many different human diseases. This project will build on Australia's strong programme of structural and cellular biology research to develop key insights ....Endosomal Protein Transport: From Molecular Structures to Biological Function. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling, homoeostasis and development. Defects in this fundamental process and subversion of it by bacterial and viral pathogens also lead to many different human diseases. This project will build on Australia's strong programme of structural and cellular biology research to develop key insights into endosomal trafficking at the molecular level. Outcomes from this work will place Australia at the forefront of international efforts to understand this essential biological process and will have important implications for future design of pharmaceuticals.Read moreRead less
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0237427
Funder
Australian Research Council
Funding Amount
$269,000.00
Summary
Equipment for Fluorescence-Based Cellular Analysis. The requested equipment is needed by a large grouping of highly productive researchers to carry out work across a very broad range of fields that is otherwise difficult or impossible to perform. The new equipment will facilitate obtaining many exciting and important outcomes, including identification of: (i) mechanisms controlling cell death, (ii) natural biological products that may have commercial applications (eg anti-fouling agents), (iii) ....Equipment for Fluorescence-Based Cellular Analysis. The requested equipment is needed by a large grouping of highly productive researchers to carry out work across a very broad range of fields that is otherwise difficult or impossible to perform. The new equipment will facilitate obtaining many exciting and important outcomes, including identification of: (i) mechanisms controlling cell death, (ii) natural biological products that may have commercial applications (eg anti-fouling agents), (iii) "probiotic" bacteria and vaccines that may be used to protect animals from disease, and (iv) mechanisms by which changes in human lens proteins contribute to the development of cataract.Read moreRead less