Biomimetic Insights from Enamel: A Nano-mechanical and Nano-structural Investigation of a Natural Ceramic-like Biocomposite. Enamel is a naturally developed example of an optimised material structure that constitutes the hardest tissue in the human body. In addition it is exposed to severe mechanical and environmental challenges and must last the lifetime of the individual and unlike other tissue is unable to heal or repair itself. Understanding the factors controlling the amazing mechanical pr ....Biomimetic Insights from Enamel: A Nano-mechanical and Nano-structural Investigation of a Natural Ceramic-like Biocomposite. Enamel is a naturally developed example of an optimised material structure that constitutes the hardest tissue in the human body. In addition it is exposed to severe mechanical and environmental challenges and must last the lifetime of the individual and unlike other tissue is unable to heal or repair itself. Understanding the factors controlling the amazing mechanical properties of this tissue will be of great benefit for the design of bio-inspired materials and be important for the development of advanced materials for which Australia already has an enviable reputation.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
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
Rare isotopes as tracers of prosthesis debris. The incidence of knee replacement surgery in Australia is 30,000 per year. Limited by wear debris, the lifespan of knee implants is only 10-15 years and can be much shorter. Due to increasing life expectancy, many patients need several surgical procedures. As a multi-disciplinary team of materials-, isotope-tracing- and medical-experts, we aim to understand and monitor wear debris in prostheses. Knee replacement surgery alone imposes a high burden o ....Rare isotopes as tracers of prosthesis debris. The incidence of knee replacement surgery in Australia is 30,000 per year. Limited by wear debris, the lifespan of knee implants is only 10-15 years and can be much shorter. Due to increasing life expectancy, many patients need several surgical procedures. As a multi-disciplinary team of materials-, isotope-tracing- and medical-experts, we aim to understand and monitor wear debris in prostheses. Knee replacement surgery alone imposes a high burden of annually half a billion dollars on the Australian health budget. Controlling and reducing wear debris in prosthesis joints would reduce these costs and improve patients' quality of life.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
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
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