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
Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematic ....Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematical model of the regulation of cell-shape and volume. The project will provide an understanding of mechanisms operating when cells and tissues are succumbing to trauma and invasion, and how to control these processes on a molecular level.Read moreRead less
Laws of attraction and repulsion: a novel family of bacterial chemo-sensors. This project aims to reveal the structural basis for the abilities of a newly characterised, widespread family of chemotaxis receptors to sense and distinguish between attractants and repellents. Many bacteria are motile. Controlling the movement of bacterial populations requires understanding of their chemosensory mechanisms. It is anticipated that this work will generate significant new knowledge in the field of signa ....Laws of attraction and repulsion: a novel family of bacterial chemo-sensors. This project aims to reveal the structural basis for the abilities of a newly characterised, widespread family of chemotaxis receptors to sense and distinguish between attractants and repellents. Many bacteria are motile. Controlling the movement of bacterial populations requires understanding of their chemosensory mechanisms. It is anticipated that this work will generate significant new knowledge in the field of signalling biology that will drive the discovery of novel chemo-effectors and the redesign of receptor specificity. Innovative use of this knowledge could be the development of new classes of repellents that are not toxic. These could be used as a means to prevent infections caused by bacterial build-up on implanted medical devices.Read moreRead less
Structural and functional studies of Helicobacter pylori flagellar motor. This project investigates the bacterial flagellar motor specialised for locomotion in viscous fluids. Its striking feature, revealed by cryo-tomography, is a complex cage-like protein scaffold that is hypothesised to stabilise the wider force-generating ring of the motor to sustain a larger turning force. The aim is to unravel the make-up of this scaffold and the structural basis for its ability to recruit more force-gener ....Structural and functional studies of Helicobacter pylori flagellar motor. This project investigates the bacterial flagellar motor specialised for locomotion in viscous fluids. Its striking feature, revealed by cryo-tomography, is a complex cage-like protein scaffold that is hypothesised to stabilise the wider force-generating ring of the motor to sustain a larger turning force. The aim is to unravel the make-up of this scaffold and the structural basis for its ability to recruit more force-generating units, in order to advance our fundamental knowledge about the mechanism of the bacterial flagellar motor, and about strategies used by nature to increase its performance under high viscosity conditions. This research is expected to add a new paradigm for how polar flagellar motors assemble and function in bacteria.
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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
Discovery Early Career Researcher Award - Grant ID: DE220100964
Funder
Australian Research Council
Funding Amount
$443,869.00
Summary
Statistical approaches for spatial genomics at single cell resolution. Cells cooperate to form complex, dynamic and varied tissue structures. This project aims to develop statistical and computational approaches to analyse spatial genomics data, a novel technology that retains vital spatial information at single cell resolution while detecting RNA molecules for hundreds of genes. Observing the molecular activity of cells in their spatial context is critical for tackling key biological questions, ....Statistical approaches for spatial genomics at single cell resolution. Cells cooperate to form complex, dynamic and varied tissue structures. This project aims to develop statistical and computational approaches to analyse spatial genomics data, a novel technology that retains vital spatial information at single cell resolution while detecting RNA molecules for hundreds of genes. Observing the molecular activity of cells in their spatial context is critical for tackling key biological questions, such as how tumour cells behave during malignancy or how stem cells determine their fate. Expected outcomes also include techniques to fully harmonise spatial and non-spatial genomics datasets, and methods toward understanding the complex relationships among cells in their environment, revealing novel cell biology.Read moreRead less
Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods ....Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods. The expected outcome is to deliver new methodology for a comprehensive understanding of the correlation between quality control machinery, stress responses and cell functions. This should provide significant benefits, including contributing to fundamental knowledge on the molecular causes of neurodegenerative diseases.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100206
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Intelligently linking nanoscience to neuroscience with glycan biology. This project aims to provide a comprehensive description of the unique cell-surface glycan expression on inflamed neurons, astrocytes, microglia and oligodendrocytes. This project will use glycan profiling data to engineer luminescent nanoparticles with superior neuroimaging qualities for cell type-specific in vivo targeting and drug delivery in the central nervous system. The project outcomes are expected to improve our fund ....Intelligently linking nanoscience to neuroscience with glycan biology. This project aims to provide a comprehensive description of the unique cell-surface glycan expression on inflamed neurons, astrocytes, microglia and oligodendrocytes. This project will use glycan profiling data to engineer luminescent nanoparticles with superior neuroimaging qualities for cell type-specific in vivo targeting and drug delivery in the central nervous system. The project outcomes are expected to improve our fundamental understanding of neurobiological cell-surfaces.Read moreRead less
A scalable, synthetic retina: signal processing in droplet systems with DNA. This project aims to design DNA-based nanotechnology for processing optical signals in synthetic biological systems. The intended outcome of this project is to develop a system for signal transduction in artificial bilayers using new DNA nanostructures. The anticipated goal of the project is to deliver: 1) light-based control of membrane protein insertion into artificial bilayers; 2) novel DNA-based pores that can trans ....A scalable, synthetic retina: signal processing in droplet systems with DNA. This project aims to design DNA-based nanotechnology for processing optical signals in synthetic biological systems. The intended outcome of this project is to develop a system for signal transduction in artificial bilayers using new DNA nanostructures. The anticipated goal of the project is to deliver: 1) light-based control of membrane protein insertion into artificial bilayers; 2) novel DNA-based pores that can transduce signals across membranes; 3) signal processing using multi-compartment biological components composed. Together, this technology allows us to use light and external signals to control biochemical pathways in synthetic systems.Read moreRead less