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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Probing Anaesthetic Effects with New Functional Imaging Paradigms. This project seeks new insights into the effects of anaesthetics on brain function and repair. Anaesthesia is used in small-animal imaging to immobilise the animal, but in many cases the anaesthesia itself affects the neurophysiological parameters under study. It has also been shown that many anaesthetics enhance recovery after brain injury in small animals. This project plans to exploit a novel functional brain-imaging technique ....Probing Anaesthetic Effects with New Functional Imaging Paradigms. This project seeks new insights into the effects of anaesthetics on brain function and repair. Anaesthesia is used in small-animal imaging to immobilise the animal, but in many cases the anaesthesia itself affects the neurophysiological parameters under study. It has also been shown that many anaesthetics enhance recovery after brain injury in small animals. This project plans to exploit a novel functional brain-imaging technique for conscious animals to gain new insights into the effects of anaesthetics on brain function and recovery from injury. The knowledge gained is expected to improve knowledge of anaesthetic action, guide future anaesthetic use in small animal imaging to improve the accuracy of image-derived research data, and help to clarify how anaesthetics confer neuroprotective effects in brain injury.Read moreRead less
Functional magnetic resonance imaging: Decoding the palimpsest. This project aims to model the dynamics of functional magnetic resonance imaging (fMRI) to image new physiology and attain higher resolution. This will enable new aspects of brain dynamics to be imaged, achieving higher resolution and improving interpretation. This project is expected to improve the use and power of fMRI, unlock new avenues for probing brain function and save experimental costs. This will have many uses in neuroscie ....Functional magnetic resonance imaging: Decoding the palimpsest. This project aims to model the dynamics of functional magnetic resonance imaging (fMRI) to image new physiology and attain higher resolution. This will enable new aspects of brain dynamics to be imaged, achieving higher resolution and improving interpretation. This project is expected to improve the use and power of fMRI, unlock new avenues for probing brain function and save experimental costs. This will have many uses in neuroscience, brain imaging technology and fMRI analysis software.Read moreRead less
The acoustics of a wide-range autonomous oscillator: how do brass players do it? While brass instruments are well understood, the complexities of the interaction with the player are not. This study will analyse how the player's lips and vocal tract interact with the instrument, leading to an understanding not only of the interesting physics involved, but to insight that will benefit players, teachers and students.
Background-free imaging of single membrane-receptors with nanophosphors. This project aims to develop nanophosphor beacons and real-time, ultrahigh-sensitivity functional imaging to provide a picture of the brain. Time-gated detection microscopy will give these nanophosphors a superior optical contrast. The nanophosphors’ antibody-targeting will image single AMPA membrane receptors in their full biological context, crucial to understanding neuronal signalling. Simultaneous imaging of receptor tr ....Background-free imaging of single membrane-receptors with nanophosphors. This project aims to develop nanophosphor beacons and real-time, ultrahigh-sensitivity functional imaging to provide a picture of the brain. Time-gated detection microscopy will give these nanophosphors a superior optical contrast. The nanophosphors’ antibody-targeting will image single AMPA membrane receptors in their full biological context, crucial to understanding neuronal signalling. Simultaneous imaging of receptor trafficking and activity in neurons will help to uncover details of the dynamic activity in the brain. This technology is expected to help understand the inner workings of the brain and provide insights into its functioning.Read moreRead less
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
Rational design of new synthetic antifreeze molecules for cryopreservation. This project aims to synthesise new carbohydrate-based surfactants optimised for use as cryoprotectants, and to accurately measure, model and optimise their performance. The project will use state-of-the-art experimental methods and advanced phase-field modelling techniques to optimise the cryoprotectants so that they reduce osmotic stress in cells and inhibit ice crystal growth during freezing and thawing. The expected ....Rational design of new synthetic antifreeze molecules for cryopreservation. This project aims to synthesise new carbohydrate-based surfactants optimised for use as cryoprotectants, and to accurately measure, model and optimise their performance. The project will use state-of-the-art experimental methods and advanced phase-field modelling techniques to optimise the cryoprotectants so that they reduce osmotic stress in cells and inhibit ice crystal growth during freezing and thawing. The expected outcomes will be novel cryoprotectants that are easy to synthesise, non-toxic and effective, opening up new possibilities for the cryopreservation of cells, organs and possibly even whole organisms. This will have broad impact in critical applications such as long-term blood storage, reproductive technology and stem cell therapy, as well as preservation of endangered species.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
PET imaging of learning-related plasticity in awake behaving rats. The objective of the project is to combine an investigation of basic learning paradigms with functional Positron emission tomography (PET) imaging in rats in order to answer critical questions about the neurobiological basis of learning and decision-making in the brain. MicroPET technology provides PET images without the confounds induced by anaesthesia. Using this technology, the project intends to observe whole-brain changes in ....PET imaging of learning-related plasticity in awake behaving rats. The objective of the project is to combine an investigation of basic learning paradigms with functional Positron emission tomography (PET) imaging in rats in order to answer critical questions about the neurobiological basis of learning and decision-making in the brain. MicroPET technology provides PET images without the confounds induced by anaesthesia. Using this technology, the project intends to observe whole-brain changes in dopamine neurotransmission in awake, behaving rats while they learn to predict motivationally relevant outcomes based on environmental cues and on their own actions (ie during Pavlovian and instrumental conditioning, respectively). The outcomes of this research may improve our understanding of the neural changes responsible for debilitating disorders of the brain and mind.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