Advanced high resolution atomic force microscopy of biomolecules in physiological environments. The proposed research is intended to explain high resolution bioimaging problems addressed only phenomenologically before. A correct physical model would help the scientific community to optimise imaging of dynamic biological systems, extending our knowledge about the way living organisms function. With dynamic bioimaging, the mechanism of certain diseases such as Alzheimer's - where biomolecule fiber ....Advanced high resolution atomic force microscopy of biomolecules in physiological environments. The proposed research is intended to explain high resolution bioimaging problems addressed only phenomenologically before. A correct physical model would help the scientific community to optimise imaging of dynamic biological systems, extending our knowledge about the way living organisms function. With dynamic bioimaging, the mechanism of certain diseases such as Alzheimer's - where biomolecule fiber formation plays a key role - can also be addressed, thus the project has even therapeutical relevance. Furthermore, adequate description of liquid phase imaging can help engineers in the design of better hardware and software solutions, for the benefit of the bio-nanotechnological industry.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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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
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
Design and Construction of Novel Thermal Interferometers. This project aims to invent thermal interferometers, which take advantage of the interference effect of thermal waves to display standing temperature interference fringes on a surface of prism. Two coherent thermal waves are input from two other surfaces of the prism in a similar way as an optical interferometer does. By inventing such a device, the project will demonstrate a new instrumentation mechanism which may lead to its applicati ....Design and Construction of Novel Thermal Interferometers. This project aims to invent thermal interferometers, which take advantage of the interference effect of thermal waves to display standing temperature interference fringes on a surface of prism. Two coherent thermal waves are input from two other surfaces of the prism in a similar way as an optical interferometer does. By inventing such a device, the project will demonstrate a new instrumentation mechanism which may lead to its application in medical technology. Furthermore, the principle of temperature localisation due to thermal interference may provide new insights to account for the cause of conformational changes of proteins that result in diseases.Read moreRead less
Optical manipulation of single molecules in nanocontainers and nanotubes. Modern medicine has benefited greatly from technological advances in instrumentation. The ability to probe and manipulate new aspects of biological function often provides unique information that can be used as the basis of new medical treatments. Recent advances in optical instrumentation and biochemical labelling has enabled the study of biological function at the single molecule level. This project proposes to develop n ....Optical manipulation of single molecules in nanocontainers and nanotubes. Modern medicine has benefited greatly from technological advances in instrumentation. The ability to probe and manipulate new aspects of biological function often provides unique information that can be used as the basis of new medical treatments. Recent advances in optical instrumentation and biochemical labelling has enabled the study of biological function at the single molecule level. This project proposes to develop new techniques in single molecule manipulation, to perform studies not easily addressable using current techniques. The proposed research will form the basis of an enabling technology for Australian researchers to make breakthroughs in biomedical research, potentially leading to improvements in healthcare.Read moreRead less