New fragment-based drug design technology by NMR spectroscopy. A new nuclear magnetic resonance (NMR) spectroscopic strategy will be developed for rapid determination of the structure and binding mode of low-molecular weight compounds bound to target proteins. Structural information obtained in this way will greatly accelerate drug development by fragment-based drug design, and NMR spectroscopy is the only method that can deliver this information in solution at atomic resolution. The impact of t ....New fragment-based drug design technology by NMR spectroscopy. A new nuclear magnetic resonance (NMR) spectroscopic strategy will be developed for rapid determination of the structure and binding mode of low-molecular weight compounds bound to target proteins. Structural information obtained in this way will greatly accelerate drug development by fragment-based drug design, and NMR spectroscopy is the only method that can deliver this information in solution at atomic resolution. The impact of the project for pharmaceutical research is further enhanced by extending the range of proteins amenable to NMR analysis by the development of new labelling strategies using stable isotopes, lanthanides and an unnatural amino acid in a state-of-the-art protein production system.Read moreRead less
3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, ....3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, and how they malfunction in disease. This project will provide a computational framework to increase the impact of this investment by integrating measurements from a range of novel technologies and developing understanding of changes in structure of large protein complexes in different functional states.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0237664
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
High Resolution Mass Spectrometer for (MS)n Chemical Characterisation. A Fourier transform ion cyclotron resonance ("FT-ICR") mass spectrometer equipped with electrospray ionisation (ESI) plus a "benchtop" matrix assisted laser desorption ionisation time of flight (MALDI-TOF) mass spectrometer are required to support the research of ca 28 research groups, including 44 postdoctoral fellows, and 138 honours and postgraduate students. By means of its high resolution and (MS)n capabilities, the FT- ....High Resolution Mass Spectrometer for (MS)n Chemical Characterisation. A Fourier transform ion cyclotron resonance ("FT-ICR") mass spectrometer equipped with electrospray ionisation (ESI) plus a "benchtop" matrix assisted laser desorption ionisation time of flight (MALDI-TOF) mass spectrometer are required to support the research of ca 28 research groups, including 44 postdoctoral fellows, and 138 honours and postgraduate students. By means of its high resolution and (MS)n capabilities, the FT-ICR-MS will provide key structural information on a wide range of synthetic and natural chemical substances, including sequence (e.g. peptides) and fragmentation patterns, while the MALDI-TOF instrument will be used primarily for high through-put proteomic analyses.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100096
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
A unique soft matter high-performance scanning probe microscopy (HP-SPM) facility. Soft matter research touches every aspect of our lives as it covers materials from the range of plastics found in cars, television sets and other mass-manufactured products, to new medical materials for tissue engineering and sensors. The proposed facility will enable Australia's leading scientists in this area to understand better how soft matter, including both biological and new advanced soft materials, behave ....A unique soft matter high-performance scanning probe microscopy (HP-SPM) facility. Soft matter research touches every aspect of our lives as it covers materials from the range of plastics found in cars, television sets and other mass-manufactured products, to new medical materials for tissue engineering and sensors. The proposed facility will enable Australia's leading scientists in this area to understand better how soft matter, including both biological and new advanced soft materials, behaves on the nano-scale level. This will put Australian researchers and engineers in a leading position for developing new treatments against cancer and other diseases, as well as harnessing the power of biology for application in areas such as waste treatment and energy production.Read moreRead less
What limits CO2 diffusion inside leaves? Dissecting the diffusion path with Arabidopsis mutants. Human induced increase in atmospheric carbon dioxide is now generally accepted as contributing to global warming. Forecasting our future impact relies on models of terrestrial photosynthesis which use a signature in the atmosphere created by plants when they discriminate against the heavy stable isotope of carbon during photosynthesis. Discrimination between isotopes is affected by carbon dioxide dif ....What limits CO2 diffusion inside leaves? Dissecting the diffusion path with Arabidopsis mutants. Human induced increase in atmospheric carbon dioxide is now generally accepted as contributing to global warming. Forecasting our future impact relies on models of terrestrial photosynthesis which use a signature in the atmosphere created by plants when they discriminate against the heavy stable isotope of carbon during photosynthesis. Discrimination between isotopes is affected by carbon dioxide diffusion within leaves and key steps in this process will be identified through the use of Arabidopsis mutants. Better representation of this process in models will improve estimates of terrestrial photosynthesis and climate change forecastsRead moreRead less
Molecular and Cellular Characterisations of the Cortical Actin Cytoskeleton in the Plant Arabidopsis thaliana. Plant cells contain extensive arrays of the cytoskeletal protein actin that attach to the plasma membrane and may play important roles in cell elongation through interactions with cortical microtubules. However, the organisation, dynamics and functions of cortical actin remain poorly understood. I will combine cell and molecular approaches to understanding cortical actin in living tissu ....Molecular and Cellular Characterisations of the Cortical Actin Cytoskeleton in the Plant Arabidopsis thaliana. Plant cells contain extensive arrays of the cytoskeletal protein actin that attach to the plasma membrane and may play important roles in cell elongation through interactions with cortical microtubules. However, the organisation, dynamics and functions of cortical actin remain poorly understood. I will combine cell and molecular approaches to understanding cortical actin in living tissue of Arabidopsis, using both wild-type and previously uncharacterised mutants, and will develop a novel mutational screening strategy to isolate mutants disrupted in plasma membrane or microtubule binding. This research will contribute significantly to a greater understanding of how the plant grows and develops.Read moreRead less
Disorder as a novel determinant of photosynthetic structure and function: an experimental study. Australia enjoys a world reputation in photosynthesis research, typified by hosting the 2001 International Photosynthesis Congress. It also has a claim to fame for theoretical work in non-equilibrium thermodynamics concerning production of disorder or entropy, yielding new insights into planetary climates. This experimental project investigates the novel relation between entropy/entropy production ....Disorder as a novel determinant of photosynthetic structure and function: an experimental study. Australia enjoys a world reputation in photosynthesis research, typified by hosting the 2001 International Photosynthesis Congress. It also has a claim to fame for theoretical work in non-equilibrium thermodynamics concerning production of disorder or entropy, yielding new insights into planetary climates. This experimental project investigates the novel relation between entropy/entropy production and the structure/function of the solar powerhouse of plants (chloroplasts), and addresses fundamental questions at the interface of biology and physics. The research explores chloroplasts as a manifestation of the all-pervading Second Law of Thermodynamics, advancing Australia's contribution to basic science and helping to train researchers.Read moreRead less
Molecular analysis of photosynthetically-linked, active CO2 uptake and CO2 signal transduction by cyanobacteria (blue-green algae). Cyanobacteria (blue-green algae) have evolved a very efficient means of capturing and concentrating CO2 for photosynthetic fixation into sugars, the basic building blocks for cell growth. This process is dependent on the operation of several unique, active uptake systems for CO2 and HCO3-, with their genetic expression regulated by CO2 supply. This proposal will cap ....Molecular analysis of photosynthetically-linked, active CO2 uptake and CO2 signal transduction by cyanobacteria (blue-green algae). Cyanobacteria (blue-green algae) have evolved a very efficient means of capturing and concentrating CO2 for photosynthetic fixation into sugars, the basic building blocks for cell growth. This process is dependent on the operation of several unique, active uptake systems for CO2 and HCO3-, with their genetic expression regulated by CO2 supply. This proposal will capitalize on our progress in describing the functional genetics of this process and aims to elucidate the mechanism of active CO2 uptake and the way that cells sense the ambient CO2 concentration. The information gained is likely to be useful for designing improved crops.Read moreRead less
Photosynthetically active bicarbonate transporters from cyanobacteria & their rational redesign for application in engineered crops that use less water. Marine blue-green algae are critical components of global primary productivity and fisheries productivity but CO2 acquisition processes in these organisms are poorly understood. Our aim is to determine the protein structure and regulatory controls present in two classes of cyanobacterial bicarbonate transporters that are required for efficient p ....Photosynthetically active bicarbonate transporters from cyanobacteria & their rational redesign for application in engineered crops that use less water. Marine blue-green algae are critical components of global primary productivity and fisheries productivity but CO2 acquisition processes in these organisms are poorly understood. Our aim is to determine the protein structure and regulatory controls present in two classes of cyanobacterial bicarbonate transporters that are required for efficient photosynthesis. This information is now critical to the our goal of redesigning these bicarbonate transporters so they will be functional in plants, thereby contributing to the applied objective of engineering crop plants that could produce good grain yields with reduced water requirements.Read moreRead less
Structure and function of heterodimeric amino acid transporters. Recently a new family of amino acid transporters has been identified, the members of which are involved in the delivery of amino acids between cells and tissues. All members display a rather unusual structure in that they require two subunits to be functional. The main aim of this study is to investigate the interaction between large and small subunits. The study will give insight how membrane proteins form complexes in the membran ....Structure and function of heterodimeric amino acid transporters. Recently a new family of amino acid transporters has been identified, the members of which are involved in the delivery of amino acids between cells and tissues. All members display a rather unusual structure in that they require two subunits to be functional. The main aim of this study is to investigate the interaction between large and small subunits. The study will give insight how membrane proteins form complexes in the membrane and how these interactions affect the function of a complex membrane protein.Read moreRead less