A World-Leading National Network for NMR in the Physical and Life Science: Very-High Field Infrastructure at Sheffield

Lead Research Organisation: University of Sheffield
Department Name: Molecular Biology and Biotechnology

Abstract

We will deliver access to state-of-the-art very high field NMR capabilities to the UK NMR and wider research community across the physical and life sciences through the upgrading of the NMR Facility at the University of Sheffield. This will comprise an existing 800 MHz system that will be upgraded with a modern cryoprobe and console and focus on solution NMR applications, especially those requiring elevated pressure. The Sheffield NMR Facility will be run by existing staff to provide expertise in solution NMR to non-NMR specialist users, and will be one component of a UK hub and spoke network of NMR instrumentation to be run for the benefit of the whole UK research community. NMR spectroscopy is the most versatile of all the analytical tools; it provides insights into molecular structure, dynamics, and interactions. The higher sensitivity and resolution delivered with ultra- and very-high field NMR are transformative, providing information not accessible at lower field strength.

The new capabilities of the Sheffield NMR Facility will support, extend and enhance research activities, both in the north and in the UK as a whole (see Academic Beneficiaries); enable and expand research in advanced chemical- and bio-materials, therapeutics, biotechnology and renewable energy; and catalyse new academic-industrial collaborations, focusing on and exploiting areas where there is excellence in the N8 and UK-wide. Examples include:

(1) Structure determination of biological and chemical molecules and supra-molecular aggregates in solution;

(2) Folding of linear polypeptides into complex biologically-active 3D structures, and the ways in which these processes can be altered or subverted in neurodegenerative diseases and cancer;

(3) Catalytic processes, and the detailed analysis of the structure and dynamics of complex materials;

(4) Metabolism within intact cells and organisms.

UK research support targets that strengthen the UK's competitive position in key priority areas. By providing ready access to state-of-the-art instrumentation and expertise, the proposed Sheffield NMR Facility will enable UK research communities to continue to make major contributions across the range of research challenges aligned with national agendas and strategic priorities, and to respond rapidly and flexibly to initiatives such as the Industrial Strategy Challenge and the Global Challenges Research Funds.
We will deliver on this major investment in NMR by:

(1) Progressing a challenging scientific agenda based on national priorities such as advanced materials, renewable energy, industrial biotechnology and synthetic biology, and core health challenges;

(2) Ensuring that the UK is at the forefront of NMR technique development in the solution state, by capitalising on our collective knowledge and experience, and providing training to the community through courses and summer schools;

(3) Attracting industrial support, partnerships and engagement, founded upon a strong collective track record of using our scientific capabilities and assets to support economic growth;

(4) Maximising the effective use of capital assets to ensure efficient provision of NMR access, building on our pioneering experience in equipment sharing, and operating and managing national facilities, within a long-term sustainability plan;

(5) Aligning with the core individual and collective institutional strategies in the N8;

(6) Developing annual reporting systems and symposia to disseminate findings and open new research strategies, and monitoring performance using defined Key Performance Indicators.

Planned Impact

The proposed Sheffield NMR Facility will, through its interaction with the internationally-leading and interdisciplinary Centres of Excellence in the N8 region and UK-wide, impact on a broad spectrum of UK industries, including:

(1) Supporting and growing the UK chemical industry. The sector has a turnover exceeding £50bn and over 180,000 employees working in 3000 organizations, and represents around 10% of value added in UK manufacturing, equivalent to 2.2% of GDP;

(2) Strengthening the UK's competitiveness in the global market for advanced functional materials, which is expected to generate revenue of £85bn by 2018 and is one of the UK government's 8 Great Technologies, representing 15% of the country's GDP. New and accelerated approaches to designing functionality into molecules, components and processes are required, which will be based on understanding structure-property-process relationships;

(3) Enhancing the UK's role in the development of renewable energy generation and storage and in the mitigation of anthropomorphic climate effects. Over the last six years, the UK's solar photovoltaic capacity has increased from virtually nothing to more than 11,000 MW, with significant economic impact (turnover > £6bn, providing > 30,000 jobs in 2013). The development of more efficient solar photovoltaic devices, and of photocatalytic processes, relies on the characterization of ultrafast charge carrier dynamics and loss processes;

(4) Providing state-of-the-art infrastructure for the UK biomedical-life science sector, which has a turnover in the region of £50bn. The life sciences cluster in the North of England alone accounts for between 21% and 23% of the UK sector, with 925 companies employing 38,000 people and generating £10.9bn in turnover. This spans Pharmaceuticals, Biotechnology, Analytics, Diagnostics, Contract research, Contract manufacturing, Medical devices, and Healthcare;

(5) Guiding advances in industrial biotechnology (IB), which is a burgeoning and a cornerstone of the European IB economy that will transform industries as varied as chemicals, waste, energy and plastics with a combined value of £81bn and 800,000 UK jobs. The N8 region is very well placed to capitalise on and contribute to this economic explosion, with its unique interdisciplinary profile in biotechnology and its strong connections with industrial stakeholders in Europe and internationally. For example the Centre of Excellence in Biopharmaceuticals alone has engaged with 52 companies, both SMEs and larger organisations, in the region, the UK and internationally;

(6) Advancing the UK's global standing in the emerging area of nanomedicines and nanomaterial-based therapies. Global clinical use of nanomedicines benefits patients daily and has considerable market value, predicted to be > £120bn this year. The development and validation of new nanomedicines and delivery technologies require optimization of product performance, and demonstration of pharmaceutically-relevant manufacturing and in-man pharmacokinetic studies. Apart from their economic impact, development and optimization of nanomedicine and nanomaterial-based therapies will have a significant impact on life expectancy and quality of life.

Publications

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Description The grant was to develop very high field NMR infrastructure at Sheffield, by upgrading our existing 800 MHz NMR spectrometer to improve its capability. This work started in Autumn 2018 and is due to finish in April 2019, so as of the time of writing (March 2019) the work is not yet complete. However it is clear that the upgraded instrument will have greatly improved throughput, and the ability to run multiple samples remotely. It has already been useful for a range of research projects ongoing in Sheffield, for example work on studying proteins that target the bacterial cell wall, and a project to understand the mechanism of the enzyme beta-phosphoglucomutase.
Exploitation Route When the work is completed, the instrument will be opened up to external users, and we hope to work with numerous external partners in making tis technology available.
Sectors Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology