Protein chips for the high-throughput study of immune complexes by mass spectrometry. Mass spectrometry is a core enabling technology for proteomics with proteins identified by molecular weight, mass maps and sequencing within the confines of a mass spectrometer. We have found conditions under which it is possible to preserve and detect protein complexes by matrix-assisted laser desorption ionization (MALDI) mass spectrometry that has promising implications for the high-throughput screening of p ....Protein chips for the high-throughput study of immune complexes by mass spectrometry. Mass spectrometry is a core enabling technology for proteomics with proteins identified by molecular weight, mass maps and sequencing within the confines of a mass spectrometer. We have found conditions under which it is possible to preserve and detect protein complexes by matrix-assisted laser desorption ionization (MALDI) mass spectrometry that has promising implications for the high-throughput screening of protein-protein interactions. Technologies pioneered by the applicant will be advanced to achieve the high-throughput analysis of antibody complexes with native gel recovered protein antigens across emerging strains of the influenza virus by means of miniature protein chips.Read moreRead less
Enabling Technologies for Motion Corrected Positron Emission Tomography (PET) of Unanaesthetized Laboratory Animals. Small animal molecular imaging is a powerful tool in biological research and drug discovery. Anaesthesia is routinely used to avoid motion distortion, but can profoundly alter the biological process studied. This research will enable quantitative imaging of neurobiological phenomena in awake laboratory animals. It will create new opportunities for Australian basic researchers to ....Enabling Technologies for Motion Corrected Positron Emission Tomography (PET) of Unanaesthetized Laboratory Animals. Small animal molecular imaging is a powerful tool in biological research and drug discovery. Anaesthesia is routinely used to avoid motion distortion, but can profoundly alter the biological process studied. This research will enable quantitative imaging of neurobiological phenomena in awake laboratory animals. It will create new opportunities for Australian basic researchers to use innovative technology with expected high economic potential, and benefit small biotech companies by facilitating pre-clinical and clinical development of new pharmaceuticals. The new motion tracking and image reconstruction technologies developed will strengthen Australia's leading position in engineering and biomedical systems development.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883030
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
High-Resolution Field Emission Scanning Electron Microscopy (FESEM) Platform for Characterisation at the Nanometre-Level. The Field Emission Scanning Electron Microscope (FESEM) is designed to provide fundamental insights into physical and biological systems though characterisation and analysis of structures on nanometre length scales. This versatile instrument will support a wide range of research projects covering all four national research priorities. These range from the characterisation of ....High-Resolution Field Emission Scanning Electron Microscopy (FESEM) Platform for Characterisation at the Nanometre-Level. The Field Emission Scanning Electron Microscope (FESEM) is designed to provide fundamental insights into physical and biological systems though characterisation and analysis of structures on nanometre length scales. This versatile instrument will support a wide range of research projects covering all four national research priorities. These range from the characterisation of light alloys to boost and intensify Australia's aluminium, magnesium and titanium alloy industries, to tissue engineering for the repair of human elastic tissues in skin, artery, bladder and lung, to the study of microtubules in plant cells for genetic manipulation of plants to withstand environmental stresses such as drought or salinity.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0236167
Funder
Australian Research Council
Funding Amount
$580,000.00
Summary
The Sydney Combinatorial Research Facility. The proposal is to establish a multidisciplinary inter-institutional research facility for solution-phase combinatorial chemistry synthesis and analysis, and medium to high throughput biological evaluation of lead compounds through fluorescence detection methods. This will be the first and only multi-user facility of its type in Sydney. It will provide through its synthetic node at NSW and Macquarie Universities and biological screening node at Univers ....The Sydney Combinatorial Research Facility. The proposal is to establish a multidisciplinary inter-institutional research facility for solution-phase combinatorial chemistry synthesis and analysis, and medium to high throughput biological evaluation of lead compounds through fluorescence detection methods. This will be the first and only multi-user facility of its type in Sydney. It will provide through its synthetic node at NSW and Macquarie Universities and biological screening node at University of Sydney an essential resource that will enable modern combinatorial techniques to be applied to chemical and drug-lead development studies in the region.Read moreRead less
Characterising post-translational modifications in bacterial proteins. This project represents the first global attempt to characterize post-translational modifications in bacterial proteins using the tools of proteomics. Modifications to proteins are key elements in altering their function. In bacteria, modifications are important in cell-cell adhesion, signalling and triggering of the immune response. Characterisation of modified proteins and their sites of modification represents an opportuni ....Characterising post-translational modifications in bacterial proteins. This project represents the first global attempt to characterize post-translational modifications in bacterial proteins using the tools of proteomics. Modifications to proteins are key elements in altering their function. In bacteria, modifications are important in cell-cell adhesion, signalling and triggering of the immune response. Characterisation of modified proteins and their sites of modification represents an opportunity to understand how bacterial cell populations communicate in the environment, as well as aid in understanding pathogenesis in medical, veterinary and food-borne pathogens. Therefore, improved vaccine targets and therapeutics, as well as method-based products, may be generated by this project.Read moreRead less
Electro-active and migratory peptides in lipid bilayers: NMR and biophysical studies. All living things are characterized by the separation of inner space from the surrounding medium by a self-assembling membrane. Selective entry and exit of water, ions and solutes is a defining feature of each type of cell. Some proteins sense the voltage difference across the cell membrane and open or close in response to voltage changes. Others, like bacterial toxins assemble in the membrane as pores, while o ....Electro-active and migratory peptides in lipid bilayers: NMR and biophysical studies. All living things are characterized by the separation of inner space from the surrounding medium by a self-assembling membrane. Selective entry and exit of water, ions and solutes is a defining feature of each type of cell. Some proteins sense the voltage difference across the cell membrane and open or close in response to voltage changes. Others, like bacterial toxins assemble in the membrane as pores, while other peptides migrate across the membrane piggy-backing their peptide cargo. The aim is to understand the molecular mechanisms in examples of these membrane-active peptides and proteins with a view to enabling rational intervention into their operation in situ in normal and disease states.Read moreRead less
NMR studies of membrane proteins and peptides in novel amphiphilic mesophases. Membrane proteins are the next frontier in structural biology. Our goal is the structural and mechanistic characterization of the proteins and peptides from platypus venom and a cardiac potassium ion channel, HERG, that has a particular role in the suppression of cardiac arrhythmias. To do this we will refine and develop methods using amphiphilic mesophases and micelles and state-of-the-art NMR spectroscopy. Electrop ....NMR studies of membrane proteins and peptides in novel amphiphilic mesophases. Membrane proteins are the next frontier in structural biology. Our goal is the structural and mechanistic characterization of the proteins and peptides from platypus venom and a cardiac potassium ion channel, HERG, that has a particular role in the suppression of cardiac arrhythmias. To do this we will refine and develop methods using amphiphilic mesophases and micelles and state-of-the-art NMR spectroscopy. Electrophysiological analysis of ion channels and interactions with toxins will relate NMR structures to function. The NMR methodologies we develop will have broad applicability to membrane proteins in general.
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Nuclear magnetic resonance (NMR) studies of complex cellular responses: isotopomer sub-spaces, 'lost' ATP and 'tunable' anisotropy. Red blood cells (RBCs) transport oxygen around the body but they have other roles that are mediated by complex interconnecting metabolic pathways that generate myriad metabolites including ATP. A longstanding conundrum is the inability to account for ~60% of ATP turnover in human RBCs. Processes that may consume this 'lost' ATP, include autonomous motion of the cel ....Nuclear magnetic resonance (NMR) studies of complex cellular responses: isotopomer sub-spaces, 'lost' ATP and 'tunable' anisotropy. Red blood cells (RBCs) transport oxygen around the body but they have other roles that are mediated by complex interconnecting metabolic pathways that generate myriad metabolites including ATP. A longstanding conundrum is the inability to account for ~60% of ATP turnover in human RBCs. Processes that may consume this 'lost' ATP, include autonomous motion of the cell membrane called 'flickering', and maintenance of the biconcave-disc shape. NMR spectroscopy of quadrupolar nuclei in chiral aligned media, and isotopomer analysis will be used to define the kinetics of metabolism and membrane processes and thus help define the molecular basis of major blood disorders. Read moreRead less
NMR Spectroscopy of Complex Cellular Processes. The Theme is the cell viewed as a complex regulated molecular assembly. The Aim is to establish an integrated mathematical model of red cell metabolism, membrane transport, shape, and mechanical properties, principally by using NMR spectroscopy. The Significance will be discovery of new aspects of cellular structure and function, and new NMR theory for molecular bioscience. Outcomes will include new NMR measurements of kinetics of metabolic reactio ....NMR Spectroscopy of Complex Cellular Processes. The Theme is the cell viewed as a complex regulated molecular assembly. The Aim is to establish an integrated mathematical model of red cell metabolism, membrane transport, shape, and mechanical properties, principally by using NMR spectroscopy. The Significance will be discovery of new aspects of cellular structure and function, and new NMR theory for molecular bioscience. Outcomes will include new NMR measurements of kinetics of metabolic reactions, rates of membrane transport, solute diffusion, and functions of key membrane- and cytoskeletal proteins. Practical applications will include strategies for modelling complex biochemical systems, and circumventing metabolic defects arising from inheritance, the environment, and therapies.Read moreRead less
Discovery and characterization of new classes of small regulatory RNAs in mammals. The project will reaffirm and enhance Australian leadership in the most rapidly developing area of molecular biological and genetic research, by the application of ultra high-throughput sequencing technologies to discovery of regulatory RNAs, thereby to identify the characteristics of important regulatory pathways that underpin mammalian development, brain function and species diversity. The results of this resear ....Discovery and characterization of new classes of small regulatory RNAs in mammals. The project will reaffirm and enhance Australian leadership in the most rapidly developing area of molecular biological and genetic research, by the application of ultra high-throughput sequencing technologies to discovery of regulatory RNAs, thereby to identify the characteristics of important regulatory pathways that underpin mammalian development, brain function and species diversity. The results of this research will have wide implications and applications in biotechnology, genetic engineering, animal breeding, medical science and advanced informatics.Read moreRead less