A Coordinated Infrastructure for NMR for the Physical and Life Sciences: Upgrade to the Ultra-high Field 950 MHz Spectrometer at Oxford

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Uncovering the dynamics and three-dimensional arrangements of the millions of biological macromolecules in a cell remains a formidable task. Yet we need to know how these molecules assemble and interact if we are to understand the emergent property called life. Although large-scale efforts, such as the human genome project, have provided us with the sets of components that make up living organisms, we are still some way from comprehending how these components come together to form the molecular machines that carry out all the basic biological functions. Similar to engineers, we need to "see" the shape of components to understand their role and place in functional assemblies. Nuclear Magnetic Resonance (NMR) spectroscopy is currently the only method that can provide us with detailed views of biological components under conditions similar to those that occur in living organisms, or even in the living cell itself. As such, NMR studies complement other structural methods which rely on creating immobilised assemblies, such as crystallography and electron microscopy. As well as structural information NMR gives unique information about the dynamic behavior of these components over time, which can be related to events such as chemical catalysis, and insight about associations occurring between components that complements information from other biophysical methods.NMR instrumentation consists of large, powerful, and very expensive magnets, and electronics that transmit and record experimental signals. In this proposal, the University of Oxford requests support from the UK Research Councils to upgrade our existing ultra-high field 950 MHz NMR system, which features the most powerful magnet in the UK, with the latest generation of high-sensitivity electronics for signal detection. This so-called "cryoprobe" upgrade will boost the measured signal by a factor of ~2-4 enhancing the quality of experimental data collected and enabling more challenging molecular systems to be studied. Coupled to an automation accessory that will allow round-the-clock use of the upgraded NMR system, our proposal represents the most cost-effective and efficient means of increasing cutting-edge NMR capacity and capability in the UK (~£535K for the proposed upgrade versus ~£5M for a similar new system).Once upgraded, 50% of the time on the 950 MHz NMR system will be made available to external users from other UK academic institutions and from industry. In particular, we aim to assist users from the south of England and Wales, for which Oxford is well placed to serve as an easily accessible regional NMR hub.