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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Description The award provided funds for the purchase of a 1.0 GHz NMR spectrometer for biomolecular NMR spectroscopy at the National Biomolecular NMR spectroscopy facility in Birmingham (HWB-NMR). A smaller proportion of the funds was given to procure hardware upgrades and peripheral kits (probeheads) for existing spectrometers at HWB-NMR. The 1.0 GHz NMR spectrometer (the most powerful of its kind available in the UK to date) has been offered for use to the UK community since January 2022. The instrument has been used primarily for structural biology. Its superior performance has been instrumental for structural and dynamic studies of low-concentrated biological solutions and large, dynamic multicomponent complexes. Notable users include University College London with studies on entire ribosomes and native proteins isolated from patients blood, and the University of Birmingham with mechanistic studies on machinery responsible for the synthesis of natural products in microorganisms.
Further, the implementation of the 1.0 GHz NMR spectrometer has established Birmingham as the best-equipped biomolecular NMR facility in the country and has laid the foundation for a Birmingham-led application for a 1.2 GHz NMR spectrometer (value of the application: 17m GBP). EPSRC has awarded a proportion of the funds necessary to procure this instrument corresponding to a value of 6m GBP. With the installation of this instrument in 2025, HWB-NMR will be hosting the two unique and best-performing NMR spectrometers for biological NMR in the UK, thus boosting the quality of its service to the UK scientific community.
In this last financial year we have completed the procurement and instalment of the last peripheral kits:
1. 0.7 mm triple-resonance MAS probe for solid-state NMR of biomolecules
2. 3.2mm triple-resonance MAS probe for solid-state NMR of biomolecules
3. Rotor test station equipped for 0.7mm MAS rotors
4. QXI-F RT probe 5mm 1H/19F/13C/15N (1H optimised 5mm quadruple resonance QXI probe designed for 1H observation with 19F, 13C and/or 15N decoupling)
With kits 1-3, we have expanded our offer to include solid-state NMR of biological samples, a powerful and fast developing technique. With kit 4, we have improved our offer for pharmaceutical screenings.
Exploitation Route HWB-NMR is a national biomolecular NMR facility providing access to top instrumentation and expertise for biological NMR to both academia and industry.
Sectors Healthcare

Manufacturing

including Industrial Biotechology

Pharmaceuticals and Medical Biotechnology

URL https://www.birmingham.ac.uk/facilities/nmr
 
Description An Integrative National Infrastructure for Ultra-High-Field NMR in the Physical and Life Sciences
Amount £6,000,000 (GBP)
Funding ID EP/X01987X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 01/2023 
End 12/2027
 
Description R-NMR 
Organisation Goethe University Frankfurt
Country Germany 
Sector Academic/University 
PI Contribution Partecipated to a consortium of 26 European and UK sites on the project described below. We contribute to Communication, dissemination and engagement as well as Education and training
Collaborator Contribution REMOTE NMR (R-NMR): MOVING NMR INFRASTRUCTURES TO REMOTE ACCESS CAPABILITIES Nuclear magnetic resonance spectroscopy (NMR) is one of the major analytical methods applied in all chemical, physical, biological, and medical sciences. NMR's leading role stems from its analytical power in terms of molecular resolution, quantification, reproducibility, and broad application envelope. It requires sophisticated and expensive equipment, operated by scientists with diverse background ranging from service-oriented researchers to highly trained experts. The aggregated capital investment in European NMR facilities, operating at local, national, and European level, exceeds 500 Million Euro. The NMR community maintains excellent networking between sites and serves a broad community within the focal points of European research interests. With the application Remote-NMR (R-NMR), we wish to establish remote access for all NMR users throughout Europe. While routine NMR applications are routine in every university and in industry, more specialized applications are performed in dedicated research infrastructures offering access and help to local and outside users. During the pandemic, NMR infrastructures slowed down their operations to variable degrees, and particularly access by remote users dropped significantly, raising the need to establish standardized procedures for remote access to improve their resilience to adverse external factors. In this proposal an inclusive network of NMR-infrastructures throughout Europe will be established, surveying if and how remote access can be made possible according to the needs of the community, and implementing GDPR at facilities and sample shipment procedures. Routines for remote NMR-usage will be established, including dissemination of research and teaching protocols, archiving of data, and sample shipment. The overall CO2 footprint of the operation of the consortium will be evaluated, as well as its reduction due to the reduction of travels.
Impact Establishment of best practise for remote access Survey of remote access feasibility and challenge Survey of CO2 footprint of NMR facilities
Start Year 2022