A Coordinated Infrastructure for NMR in the Physical and Life Sciences: A 1 GHz Spectrometer at Birmingham

Lead Research Organisation: University of Birmingham
Department Name: Institute of Cancer and Genomic Sciences

Abstract

Birmingham houses and supports the Henry Wellcome Building for Biomolecular NMR (HWB-NMR), which since 2004 has provided a durable, state-of-the-art NMR service at 600, 800 and 900MHz for UK users. With support of the Wellcome Trust, the facility offers 70% of its available high-field NMR time free of charge to external users with high-quality projects and has expert support staff in place. HWB-NMR has hosted >50 research groups from laboratories across the UK, thus assuring UK leadership in ultra-high-field NMR and has regularly been part of EU access networks.
The popularity and importance of this facility for the UK NMR community is well evidenced by recent reviews, which qualified its services as "the vital scientific resource in UK" and "an excellent national facility which is clearly heavily used"; the Wellcome Trust renewed funding of the HWB-NMR operations for the period 2018-2023.
HWB-NMR proposes the addition of a 1GHz spectrometer, that will provide UK users with a unique line-up of NMR instruments covering 600, 800, 900MHz and 1GHz spectrometers, primarily for biomedical applications. By providing these services at one location, and with the combined support of research councils and the Wellcome Trust, a unique resource will be created that will put the UK NMR community at the forefront of NMR research, both nationally and internationally.
Specific services in Birmingham will include tracer-based and real-time metabolism, for which we will offer access to micro-cryoprobes at 600, 800MHz and 1GHz for ultimate mass sensitivity and will develop NMR methods that facilitate this line of research.
By forming a strategic alliance with the structural biology research at the University of Leicester (Prof Geerten Vuister, to be appointed as liaising visiting professor) we will also be able to offer specific expertise in NMR methodology, both in NMR pulse sequences and computational aspects (BBSRC funded), drug discovery and NMR software development via the CCPN project (MRC funded). With CCPNs 28 national and international partners and its extensive outreach programme, the 1GHz spectrometer will be firmly embedded in the NMR community. University-provided research support will particularly focus on methodology developments that benefit from the unique range of NMR instrumentation at HWB-NMR.
The direct interactions between Birmingham and Leicester in highly advanced NMR technology also aim to further strengthen their existing efforts in equipment and expertise sharing, as exemplified by the recent successful establishment of a shared cryo-EM facility across the Midlands universities. Jointly, the NMR and EM techniques contribute to the goal of integrated structural biology approaches for studying the molecular mechanisms that underpin both normal and aberrant cellular functioning.

Planned Impact

Funding of the coordinated UK NMR infrastructure will provide for UK-wide access to new state-of-the-art NMR capabilities and technology. It will generate very significant impact for the UK physical and life sciences, as well as for UK industry, and greatly stimulate the education and training of the next generation of our scientists.

The impact extends to a number of areas:

1. To increase effectiveness, sharing and outputs through coordinated networking activities
The NMR community recognises the need to coordinate single-point access for NMR infrastructures in the UK. For this a portal will be developed, providing relevant information about capacity, instrumentation, availability and scheduling, accounting, KPIs, as well as costs or other requirements for access. Such a single point access portal will greatly facilitate the process by which advanced NMR experiments at very-high and ultra-high field could be incorporated in the research programmes of non-expert users. This would also facilitate access to new and existing NMR services by industry, thus increasing the likelihood and ease for industry to engage in novel approaches.

2. To stimulate the development of methodology and expertise
A highly technologically advanced experimental technique, such as NMR, requires continuing attention to, and implementation of, the latest progress in experimentation together with the development of bespoke solutions for individual scientific problems. By applying the latest developments and sharing this expertise and the newly developed methodologies across the different sites of the coordinated NMR infrastructure, the speed of development and quality of the science are greatly enhanced.

3. To improve training and sharing of best practices
Members of HWB-NMR have trained >20 PhDs since the start of the facility. A strong training programme is in place, offered by various staff members. HWB-NMR has also organised biennial Bootcamps and in the future will offer such training courses annually, jointly organised with PIs from Leicester. The new resource will provide an even more stimulating environment to attract PhDs, which will underpin key research activities in many of the UK's economically important sectors, such as pharma, biotech and nanotechnology.

4. To increase the quality of research of the scientific and industrial communities via suitable engagement and outreach
The new capabilities in Birmingham will provide a line-up of NMR instruments from 600-800-900-1000MHz, for the full range of state-of-the-art solution-state NMR projects. This will facilitate new research in protein biochemistry, related to drug discovery and emerging fields in metabolism. By sharing access to the technologically advanced methodologies, the impact for the UK society is maximised, both in the realm of research as well as industry, thus contributing to the UK economic viability and overall well-being.

5. To inform the general public via suitable outreach activities
Outreach activities will include scientific outreach via publications and presentations at conferences, annual meetings for the NMR community facilitated by CCPN and HWB-NMR funding, web-sites by CCPN and by HWB-NMR. The HWB-NMR web page includes a newsletter that gets regularly updated, and lists publications by facility users. We will host regular school visits showing the new instrument, offering pupils a first-hand research experience. HWB-NMR runs annual training courses and larger 'bootcamp' courses at least every second year. Outstanding research results will be disseminated via the respective press offices.

Publications

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