NMR-BASE: Nuclear Magnetic Resonance for Biomolecule Analysis in Supported Environments

The biggest challenge in the invention of new biomedicines and biomaterials is understanding how they function at a molecular level in the context for which they are designed to work. While it is possible and necessary to examine such materials in isolation, their true purpose is revealed in their real living contexts or mimics of these. To bridge the gap that exists at the level of how designed medicines work, the NMR-BASE facility will be established to help users "see" the behaviour of their molecules in complex matrices, those that are significant in the context of therapeutic purpose. NMR-BASE will be established for the UK scientific community by providing researchers with access to state-of-the-art equipment to examine the fine details of molecular structure and behaviour in ways which will help the molecule design process to progress. The equipment will be suitable for the widest range of sample types and will be capable of supporting live cells as well as providing access to the study of tissues, gels and other "soft" materials that form the basis of many biological materials and systems. The equipment will enable a variety of scientific approaches to be used for studying molecules in their true contexts and will benefit the design process for new medicines and biomaterials. It will provide new training opportunities for a wide UK user base including PhD students both locally and nationally, providing access to unique equipment for their research along with the staff to support them. The equipment will be housed within the NMR Facility at the University of Strathclyde, a world-leading technological university which has the skills and expertise required to host and run NMR-BASE optimally.

NMR-BASE is a Nuclear Magnetic Resonance (NMR) spectroscopy platform utilizing Bruker QCI-F cryoprobe with InsightCell, high resolution HX mas-probe (HX HR-MAS) and solution phase capabilities supported by AVANCE NEO radio-frequency electronics and cooled SampleCase for automated data acquisition under flow control, in soft-matter or in standard solutions and offering up to four-fold in proton and ten-fold in fluorine NMR signal sensitivity enhancement over standard NMR technology of a similar configuration. NMR-BASE will supply multi-channel transceiver capability for parallel NMR data acquisition across multiple NMR frequency ranges with time-resolved data sampling. The QCI-F probe coupled with InsightCell or the use of HX HR-MAS will provide flow or stand-alone capability for NMR spectroscopy with enhanced sensitivity in solution, cell, extra-cellular matrix or tissue environments. The proposal will allow connected studies of biomaterials and biomolecular systems to be carried out within a single laboratory both in vitro and in cell or cell-like contexts thereby translating knowledge from one context to other, more native environments for which the molecules are designed. Scientific themes include the study of spin-isotope (NMR visible) enriched nucleic acid therapeutics, including anti-infective therapeutics (for example using fluorine as a background free NMR tag in nucleic acids and molecules designed to recognise nucleic acids), examining biomaterials, such as silk engineered for scaffold construction to support stem-cell growth, examining the behaviour of nanomedicine bioconjugates and exploring the landscape of new pharmaceuticals designed to recognise hard-to-target biomolecules including intrinsically disordered proteins, IDPs. The platform will provide wide opportunities for both local researchers and those from across the UK to use NMR spectroscopy as a means of investigating a wide range of biologics in more challenging, heterogenous environment