Reading the sequence of a single molecule of DNA . This project seeks to develop technology capable of accurately reading the sequence of a single DNA molecule for the first time. This is possible by combining state-of-the-art methods in DNA self-assembly, single-molecule fluorescence microscopy and bioelectronics, to overcome fundamental limits in current technologies.
The outcome of accurate DNA sequencing at single molecule resolution, promises ground-breaking biological insight from a more ....Reading the sequence of a single molecule of DNA . This project seeks to develop technology capable of accurately reading the sequence of a single DNA molecule for the first time. This is possible by combining state-of-the-art methods in DNA self-assembly, single-molecule fluorescence microscopy and bioelectronics, to overcome fundamental limits in current technologies.
The outcome of accurate DNA sequencing at single molecule resolution, promises ground-breaking biological insight from a more fine-grained view of the genetic world, game-changing technologies such as point-of-care genomics and in turn a substantial impact on the rapidly growing multi-billion-dollar DNA sequencing market. Read moreRead less
The geometry of genome access: lessons from HIV. Access to the cell’s nucleus, and hence its genome, is of deep scientific and commercial significance. It is controlled by a phase-separated diffusion barrier within the nuclear pore complex. Recent evidence, however, has shown that HIV can cross this barrier with its protective capsid intact, despite it being over one thousand times larger than the limit for passive transport. Combining concepts from soft-matter physics with recombinant assays, t ....The geometry of genome access: lessons from HIV. Access to the cell’s nucleus, and hence its genome, is of deep scientific and commercial significance. It is controlled by a phase-separated diffusion barrier within the nuclear pore complex. Recent evidence, however, has shown that HIV can cross this barrier with its protective capsid intact, despite it being over one thousand times larger than the limit for passive transport. Combining concepts from soft-matter physics with recombinant assays, this project aims to uncover the link between the unique geometry of HIV capsids and their ability to subvert the nucleus’ defenses. The expected outcome is a step-change in the understanding of nuclear access control, with downstream benefits to virology, bio-engineering and bio-technology.Read moreRead less
Biophysics of the brain’s waste disposal system: Understanding why we sleep. This project aims to develop a new biophysical model of the brain, founded on the recently discovered glymphatic system responsible for waste disposal during sleep. It sets out to formulate, analyse, and validate rigorous new multiscale quantitative modelling – to advance the study of sleep and brain clearance dynamics, at timescales from hours to decades. Among expected outcomes are powerful models ready for applicatio ....Biophysics of the brain’s waste disposal system: Understanding why we sleep. This project aims to develop a new biophysical model of the brain, founded on the recently discovered glymphatic system responsible for waste disposal during sleep. It sets out to formulate, analyse, and validate rigorous new multiscale quantitative modelling – to advance the study of sleep and brain clearance dynamics, at timescales from hours to decades. Among expected outcomes are powerful models ready for application at both population and individual level, and testable predictions concerning the sleep patterns that lead to aggregation of waste in the brain and eventual cognitive decline. Project outcomes should also benefit society and the economy though translation into interventions for sleep disturbance – in future applied research.Read moreRead less
Seeing is believing: Microscopy-capable single-molecule bioelectronics. This project aims to create new biophysical tools for single-molecule sensing by advancing the state-of-the-art in nanoscale bioelectronic devices. The goal is to generate novel bioelectronic devices optimised for fabrication on microscope coverslip (170 micron glass) for compatibility with new low-cost platforms for advanced biological microscopy. Expected outcomes include the first organic electrochemical transistors inter ....Seeing is believing: Microscopy-capable single-molecule bioelectronics. This project aims to create new biophysical tools for single-molecule sensing by advancing the state-of-the-art in nanoscale bioelectronic devices. The goal is to generate novel bioelectronic devices optimised for fabrication on microscope coverslip (170 micron glass) for compatibility with new low-cost platforms for advanced biological microscopy. Expected outcomes include the first organic electrochemical transistors interfaced to constrained area lipid bilayers for studying membrane proteins at single-molecule level and nanoscale transistors for electrostatically detecting motile microtubules in in-vitro molecular motor assays for biocomputation. The intended benefit is innovation in capabilities and manufacturing of bioelectronics.Read moreRead less
Creation of a super-resolution map of the bacterial cytokinesis machinery . Cell division is a fundamental process essential for life. Yet our understanding of this process on a molecular level is limited, mostly hampered by the inability to visualize the different components of the division machinery inside these tiny cells with adequate resolution. To overcome this barrier, capitalizing on recent advancements in imaging and molecular technologies combined with innovative engineering, this proj ....Creation of a super-resolution map of the bacterial cytokinesis machinery . Cell division is a fundamental process essential for life. Yet our understanding of this process on a molecular level is limited, mostly hampered by the inability to visualize the different components of the division machinery inside these tiny cells with adequate resolution. To overcome this barrier, capitalizing on recent advancements in imaging and molecular technologies combined with innovative engineering, this project aims to create a spatial and temporal map of the division machinery inside bacterial cells at unprecedented resolution. The expected outcomes are new knowledge on the mechanism of bacterial division and technological advances in biological imaging, informing applications in a wide variety of sectors.Read moreRead less
5D Imaging Flow Cytometry for in vivo Quantification of Biological Fluids. Rapid and accurate quantification of live biological fluid properties at sub-cellular and molecular levels forms the bedrock of biofluidic sciences. Majority of the biofluidic devices rely on quantifying biological fluids after its removal from the body in an in vitro Flow Cytometer (FC). FC faces many caveats i.e. biological degradation and small volume etc. In this project, we shall engineer the first in vivo 5D imaging ....5D Imaging Flow Cytometry for in vivo Quantification of Biological Fluids. Rapid and accurate quantification of live biological fluid properties at sub-cellular and molecular levels forms the bedrock of biofluidic sciences. Majority of the biofluidic devices rely on quantifying biological fluids after its removal from the body in an in vitro Flow Cytometer (FC). FC faces many caveats i.e. biological degradation and small volume etc. In this project, we shall engineer the first in vivo 5D imaging flow cytometer (5D IFC) capable of continuous assessment of potentially entire blood volume in a living mice without removing fluid out of the body. The project represents a major advancement beyond any existing flow cytometer and overcome the engineering limits of state-of-art laser scanning imaging devices.Read moreRead less
The colour of cellular aging: a deep probe of cellular processes. Understanding why we age and whether aging is preventable are profound research challenges, which must be first tackled at a cellular level. Building on our advances in non-invasive colour monitoring of cell function, this project aims to uncover intimate links between cellular processes and aging in cells that must survive for many decades such as oocytes and neurons. We will explore the tantalising possibility to rejuvenate such ....The colour of cellular aging: a deep probe of cellular processes. Understanding why we age and whether aging is preventable are profound research challenges, which must be first tackled at a cellular level. Building on our advances in non-invasive colour monitoring of cell function, this project aims to uncover intimate links between cellular processes and aging in cells that must survive for many decades such as oocytes and neurons. We will explore the tantalising possibility to rejuvenate such aged cells by interfering with molecular master switches of aging. A unique machine learning approach will be applied for finding the most effective interventions. The results will have broad impact beyond the science of aging, in the areas of female fertility, neurodegeneration and immunity.
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Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiolo ....Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiological stimuli to control electrical signalling the body. Our results will provide benefits in the form of basic understanding relevant to ion transport phenomena in biological systems, and atomic-level views of nervous system function to guide future directions in pharmacology.Read moreRead less
Comparing properties of innate immune proteins of bats and humans. Supra-molecular protein complexes known as signalosomes drive our innate immune response by forming large signaling hubs capable of recruiting downstream effectors. This project aims to compare the properties and structure of human and bat signalosomes and discover the molecular origins of the “supra-immunity” of bats. In this context, the project expects to generate new knowledge concerning the fundamental molecular mechanisms t ....Comparing properties of innate immune proteins of bats and humans. Supra-molecular protein complexes known as signalosomes drive our innate immune response by forming large signaling hubs capable of recruiting downstream effectors. This project aims to compare the properties and structure of human and bat signalosomes and discover the molecular origins of the “supra-immunity” of bats. In this context, the project expects to generate new knowledge concerning the fundamental molecular mechanisms that regulate the signalosomes. The intended outcome is to answer the long-standing question of control of speed and amplitude of innate immune response at the molecular level. Both locally and internationally, this new approach should provide benefits across structural biology, molecular evolution and biotechnology.Read moreRead less
Violation of fundamental symmetries in atoms, molecules and nuclei. This theoretical project aims to predict enhanced effects of parity (P), time reversal (T), CP and Lorentz invariance violation, which may be measured using atomic spectroscopy and nuclear physics methods. This project expects to contribute to search for physics beyond standard model, including standard model extensions predicting axion, dark matter and T,P-violating electric dipole moments. Expected outcomes include predictions ....Violation of fundamental symmetries in atoms, molecules and nuclei. This theoretical project aims to predict enhanced effects of parity (P), time reversal (T), CP and Lorentz invariance violation, which may be measured using atomic spectroscopy and nuclear physics methods. This project expects to contribute to search for physics beyond standard model, including standard model extensions predicting axion, dark matter and T,P-violating electric dipole moments. Expected outcomes include predictions of new enhanced effects in nuclei, atoms and molecules. By-products and benefits include development of high precision computer codes for atomic calculations, which are expected to have numerous applications including photon and electron processes, properties of superheavy elements and atomic clocks.Read moreRead less