Force microscopy with arbitrary optically-trapped probes and application to internal mechanics of cells. The ability to perform micromanipulation on particles, macromolecules, subcellular organelles, or whole cells is fundamental in elucidating processes such as chromosome movement during cell division, and movement of cell components in and out of the cell. The recent advances in optical tweezers have allowed this type of micromanipulation to approach reality. However, determination of the true ....Force microscopy with arbitrary optically-trapped probes and application to internal mechanics of cells. The ability to perform micromanipulation on particles, macromolecules, subcellular organelles, or whole cells is fundamental in elucidating processes such as chromosome movement during cell division, and movement of cell components in and out of the cell. The recent advances in optical tweezers have allowed this type of micromanipulation to approach reality. However, determination of the true optical force is critical for this technique to reach its full potential. This project will develop novel techniques to quantitatively determine the absolute optical force applied to the cell component using the process of ingestion (phagocytosis) as a proof-of-principle test, and measure forces in chromosome movement and vesicle transport within cells.Read moreRead less
Keeping forces local for epithelial homeostasis. This project probes how epithelial cells use mechanical forces to communicate with one another in biological life. It tests the novel concept that negative feedback is a critical, hitherto unappreciated dimension in mechanical communication, which acts to ensure proportionate responses for homeostasis. It will generate fundamental new knowledge in biology using an innovative combination of cellular and biophysical experiments and physical theory. ....Keeping forces local for epithelial homeostasis. This project probes how epithelial cells use mechanical forces to communicate with one another in biological life. It tests the novel concept that negative feedback is a critical, hitherto unappreciated dimension in mechanical communication, which acts to ensure proportionate responses for homeostasis. It will generate fundamental new knowledge in biology using an innovative combination of cellular and biophysical experiments and physical theory. The expected outcomes are fundamental new knowledge, interdisciplinary training for young scientists, new national research capacity and growing international collaborations. It will benefit Australia by enhancing its scientific world linkage, status in scientific leadership and research capacity.Read moreRead less
Shear stimulated Brillouin microscopy for cell mechanobiology. This project aims to develop novel technology for non-contact imaging of micro-mechanical properties in cells and tissues to answer fundamental questions of cell mechnanobiology. Based on principles of Brillouin light scattering, the project takes advantage of a radio-frequency lock-in detection scheme. The project will result in a real-time, high-sensitivity, non-contact 3D imaging solution for spatial characterisation of cell's loc ....Shear stimulated Brillouin microscopy for cell mechanobiology. This project aims to develop novel technology for non-contact imaging of micro-mechanical properties in cells and tissues to answer fundamental questions of cell mechnanobiology. Based on principles of Brillouin light scattering, the project takes advantage of a radio-frequency lock-in detection scheme. The project will result in a real-time, high-sensitivity, non-contact 3D imaging solution for spatial characterisation of cell's local stiffness and compressibility. This will underpin the advancement of knowledge in the area of cell mechanobiology and the investigation of diseases, where microscale changes in cell mechanical properties lead to cell dysfunction and apoptosis.Read moreRead less
NMR of enzymic reactions and membrane transport in cells: dynamic nuclear polarization, quadrupolar relaxation, and computer modelling. This project will investigate the kinetics of urea transport and the glyoxalase pathway in human red blood cells using 13C rapid-dissolution dynamic nuclear polarisation NMR spectroscopy, which enhances 13C-detection 10,000 fold. Thus cellular processes will be studied on the one-second-to-four minute timescale. Also, relaxation analysis of the 133Cs+ quadrupola ....NMR of enzymic reactions and membrane transport in cells: dynamic nuclear polarization, quadrupolar relaxation, and computer modelling. This project will investigate the kinetics of urea transport and the glyoxalase pathway in human red blood cells using 13C rapid-dissolution dynamic nuclear polarisation NMR spectroscopy, which enhances 13C-detection 10,000 fold. Thus cellular processes will be studied on the one-second-to-four minute timescale. Also, relaxation analysis of the 133Cs+ quadrupolar nucleus will probe the energy cost of shape and membrane fluctuations in the cells. Outcomes will include how changes in these fast processes can distinguish normal from diseased cells, and new NMR methods for studying cells, multi-parameter NMR-data analysis, and mathematically modeling cellular events to predict responses to physical changes and drug interactions will emerge.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100132
Funder
Australian Research Council
Funding Amount
$860,000.00
Summary
3D Cryo-FIBSEM Imaging Facility for Biological and Material Sciences. 3D Cryo-FIBSEM imaging facility for biological and material sciences: The Cryo-Focused Ion Beam Scanning Electron Microscope (Cryo-FIBSEM) will reveal isometric 3D information on the structure and composition of specimens at the nanometre scale. The cryo-FIBSEM will be the first instrument of this type in Australia able to operate in a low temperature cryogenic mode. This will enable the imaging of vitrified biological materia ....3D Cryo-FIBSEM Imaging Facility for Biological and Material Sciences. 3D Cryo-FIBSEM imaging facility for biological and material sciences: The Cryo-Focused Ion Beam Scanning Electron Microscope (Cryo-FIBSEM) will reveal isometric 3D information on the structure and composition of specimens at the nanometre scale. The cryo-FIBSEM will be the first instrument of this type in Australia able to operate in a low temperature cryogenic mode. This will enable the imaging of vitrified biological materials in a near native state and of non-biological material to allow imaging of, for example, fluids, emulsions, gels and interfaces between biological and non-biological materials. Synergistic workflows incorporating unique high-end microscopes will enable the study of complex biological structures in their native context and atomic scale imaging of beam sensitive materials.Read moreRead less
Single-molecule view of actin-tropomyosin filament dynamics. This project aims to develop a microscopy platform to resolve how filaments of the cytoskeleton, the cell's internal scaffolding, are assembled. This technology will then be used to understand how drugs can target specific components and functions of the cytoskeleton that are hijacked in cancer cells.
Imaging the action of antimicrobial peptides in living cells. The purpose of this project to use a special magnifying glass to watch molecules invading and killing cells. The outcome will be to identify the mechanism of cell killing to help in the future design of better antibiotics.
Predicting the evolution of the influenza virus on mass. Understanding viral reassortment is essential for the development of efficacious vaccines and to prepare for a future influenza pandemic. The research will improve our ability to monitor the evolution of reassorted influenza virus strains using new computer algorithms in concert with the application of bioinformatics and analytical technologies.
Discovery Early Career Researcher Award - Grant ID: DE130100251
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Biophysical mechanisms regulating early T cell signalling events. T cell activation in response to foreign pathogens or cancer cells requires a complex set of protein interactions which must be controlled in space and time. This project will use new microscopy methods with single-molecule sensitivity to determine how the cell membrane and protein clustering regulate these interactions.
Synthetic leukocytes: bio-inspired DNA nanorobots powered by flow. Inspired by the way white blood cells roll along blood vessel walls, our goal is to build DNA nanorobots that roll along surfaces in flow. We take a synthetic biology approach to using biomolecules, such as DNA and proteins, to build functional particles and surfaces. To achieve this, we will combine our teams’ technological advances in DNA nanotechnology, plasma-activation for biomolecule immobilisation, and microfluidic devices ....Synthetic leukocytes: bio-inspired DNA nanorobots powered by flow. Inspired by the way white blood cells roll along blood vessel walls, our goal is to build DNA nanorobots that roll along surfaces in flow. We take a synthetic biology approach to using biomolecules, such as DNA and proteins, to build functional particles and surfaces. To achieve this, we will combine our teams’ technological advances in DNA nanotechnology, plasma-activation for biomolecule immobilisation, and microfluidic devices. This project will contribute new methods for synthetic particle motion in flow and provide new insights into biomolecule interactions and motion. Ultimately, this will allow us to harness rolling for the delivery of synthetic nanorobots for detection and remediation in flow systems, such as the body.Read moreRead less