A National Network for Applications of High-Field NMR in the Life and Physical Sciences
Lead Research Organisation:
University of Edinburgh
Department Name: Sch of Chemistry
Abstract
Nuclear Magnetic Resonance (NMR) spectroscopy is a very powerful technique used in many fields of physical and life sciences, including all branches of chemistry, material sciences and biology. It provides wealth of information about (bio)molecules in solution and materials and insoluble molecules in solid state.
Increasing the operating frequency of NMR spectrometers leads to higher sensitivity and resolution. Both are required when working with small (tens of micrograms) amounts of sample, or with large biomacromolecules (proteins, DNA, carbohydrates). Similarly, and especially for some nuclei, solid- state NMR accrues additional benefits at higher frequencies. There are therefore instances where only high-field spectrometers can solve a particular problem.
However, very-high field and ultra-high field spectrometers come at a cost, largely associated with the development and production of their superconducting magnets. It is therefore imperative that such instrumentation is used efficiently through sharing by many research groups. Modern NMR spectrometers are versatile pieces of equipment that can be customised to tackle a range of samples, so sharing across disciplines and applications (e.g. liquid- vs solid-state) is possible.
Spectroscopists from across the UK working in a wide-range of scientific disciplines have therefore agreed to work towards a coordinated strategy for sharing very-high and ultra-high field NMR equipment to underpin fundamental and applied sciences in a wide range of areas, ranging from battery and solar panel research, enzyme catalysis, drug discovery, food security, understanding disease or characterisation of environmental matrices. By sharing technologically advanced methodologies, the impact on the UK society will be maximised, both in the academia and industry, thus contributing to the UK economic viability and overall well-being.
As part of this strategy, Scottish NMR researchers representing all Scottish universities and the CRUK Beatson Institute, have decided to establish Scottish High Field (SHF) NMR Centre around the upgraded 800 MHz NMR spectrometer housed in the SoC at UoE.
This upgrade will equip the spectrometer with up-to-date NMR capabilities for liquid- and solid-state experiments. This involves installation of two CryoProbes, MAS controller, high power 1H amplifier and three solid-state probes in Year 1, followed by the upgrade of the console in Year 3 to guarantee continued operation of the Centre beyond the duration of the grant.
Equipping this spectrometer with the latest technology and utilising the existing magnet is the most economical option that will fulfil our aim: to provide cutting edge support in liquid- and solid-state NMR to physical and life sciences researchers to deliver significant academic and industrial impact.
The measurement time on this upgraded 800-MHz liquids/solid-state NMR spectrometer will be shared between researchers from all Scottish universities, CRUK Beatson Institute and UoE researchers. Sustained operation of the Centre will be guaranteed by the financial support of participating institutions and umbrella organisations of life and chemical sciences in Scotland, SULSA and ScotCHEM. Importantly, the Centre will be operated by staff from all participating institutions.
Using the Centre as the focal point, a hub and spoke model will be used to manage access to the mid- to high-magnetic field NMR spectrometers in Scotland. This will optimise access to NMR equipment and facilitate access to ultra-high field spectrometers in England, foster day-to-day cooperation, ensure exchange of information and dissemination of best practise.
The SHF NMR Centre will transform the way high-field NMR is applied to chemistry, biology, environmental and material sciences in academia and industry. It will form a platform for interactions with other regional and national very-high field and ultra-high field UK NMR centres.
Increasing the operating frequency of NMR spectrometers leads to higher sensitivity and resolution. Both are required when working with small (tens of micrograms) amounts of sample, or with large biomacromolecules (proteins, DNA, carbohydrates). Similarly, and especially for some nuclei, solid- state NMR accrues additional benefits at higher frequencies. There are therefore instances where only high-field spectrometers can solve a particular problem.
However, very-high field and ultra-high field spectrometers come at a cost, largely associated with the development and production of their superconducting magnets. It is therefore imperative that such instrumentation is used efficiently through sharing by many research groups. Modern NMR spectrometers are versatile pieces of equipment that can be customised to tackle a range of samples, so sharing across disciplines and applications (e.g. liquid- vs solid-state) is possible.
Spectroscopists from across the UK working in a wide-range of scientific disciplines have therefore agreed to work towards a coordinated strategy for sharing very-high and ultra-high field NMR equipment to underpin fundamental and applied sciences in a wide range of areas, ranging from battery and solar panel research, enzyme catalysis, drug discovery, food security, understanding disease or characterisation of environmental matrices. By sharing technologically advanced methodologies, the impact on the UK society will be maximised, both in the academia and industry, thus contributing to the UK economic viability and overall well-being.
As part of this strategy, Scottish NMR researchers representing all Scottish universities and the CRUK Beatson Institute, have decided to establish Scottish High Field (SHF) NMR Centre around the upgraded 800 MHz NMR spectrometer housed in the SoC at UoE.
This upgrade will equip the spectrometer with up-to-date NMR capabilities for liquid- and solid-state experiments. This involves installation of two CryoProbes, MAS controller, high power 1H amplifier and three solid-state probes in Year 1, followed by the upgrade of the console in Year 3 to guarantee continued operation of the Centre beyond the duration of the grant.
Equipping this spectrometer with the latest technology and utilising the existing magnet is the most economical option that will fulfil our aim: to provide cutting edge support in liquid- and solid-state NMR to physical and life sciences researchers to deliver significant academic and industrial impact.
The measurement time on this upgraded 800-MHz liquids/solid-state NMR spectrometer will be shared between researchers from all Scottish universities, CRUK Beatson Institute and UoE researchers. Sustained operation of the Centre will be guaranteed by the financial support of participating institutions and umbrella organisations of life and chemical sciences in Scotland, SULSA and ScotCHEM. Importantly, the Centre will be operated by staff from all participating institutions.
Using the Centre as the focal point, a hub and spoke model will be used to manage access to the mid- to high-magnetic field NMR spectrometers in Scotland. This will optimise access to NMR equipment and facilitate access to ultra-high field spectrometers in England, foster day-to-day cooperation, ensure exchange of information and dissemination of best practise.
The SHF NMR Centre will transform the way high-field NMR is applied to chemistry, biology, environmental and material sciences in academia and industry. It will form a platform for interactions with other regional and national very-high field and ultra-high field UK NMR centres.
Planned Impact
In this proposal we aim to establish the Scottish High Field NMR Centre around the upgraded 800 MHz NMR instrument to strengthen the existing collaborations between individual laboratories. The Centre will operate in a hub and spoke mode for high field NMR in Scotland.
The impact of these changes will be significant as the Scottish High Field NMR Centre will
- bring new capabilities to Scottish researchers - in particular with the addition of solid-state NMR - and allow the investigations of large biomolecular assemblies, enhancing productivity and impact of their research.
- secure the much needed long term access to cutting edge NMR equipment by sustaining the operation of the laboratory for the next 10-12 years.
- bring substantial benefits to the operation of Scottish NMR laboratories through closer interdisciplinary collaboration, expertise sharing.
- guarantee access to the most suitable NMR equipment thus avoiding to need to duplicate specialised equipment in every laboratory. It therefore will have tangible economic benefits.
Our support for the NOMAD software package could provide a tipping point for its wider use in the NMR community and help the developers to realise their commercial ambitions. We strongly believe in this product, as it benefits all who come in contact with modern-day NMR laboratories: NMR personnel, NMR users and PIs. Their increase efficiencies, although difficult to put monetary value on at the moment, could be substantial.
In addition to everyday impact on the operation of NMR laboratories and the scientific outputs produced by their members, establishing the Scottish High Field NMR Centre will benefit numerous researchers who use NMR in their research and thus the impact they produce will be strengthen by the enhanced capability of our support.
As outlined in the Pathway to Impact, the important part of our impact strategy is a direct engagement with industry, SMEs in particular; we will facilitate the access to our equipment and expertise. We will thus directly contribute towards their economic success, strengthening their position in the competitive market and ultimately benefiting the UK economy.
Through our high-profile materials research we have engaged with international and local companies such as British Petroleum, Sasol and Cemex, contributing to the development of their products.
As many of our research themes are rooted in biological research, their ultimate impact will be in improved health and well-being of society. Examples of what we achieved in this area so far, are document in the Case for Support and include our engagement with Edinburgh Medical Imaging, Gemini Therapeutics, Invizius, or Ingenza.
Our environmental chemistry research will have impact on the quality of our environment and represents important societal impact.
Our coordinated efforts to educate future generations of NMR scientists and NMR users, will highly benefit their future careers, and thus contribute to their individual impact on the wealth and well-being of society. Our engagements with high-school students will encourage more to take part in this exciting and rewarding endeavour.
The impact of these changes will be significant as the Scottish High Field NMR Centre will
- bring new capabilities to Scottish researchers - in particular with the addition of solid-state NMR - and allow the investigations of large biomolecular assemblies, enhancing productivity and impact of their research.
- secure the much needed long term access to cutting edge NMR equipment by sustaining the operation of the laboratory for the next 10-12 years.
- bring substantial benefits to the operation of Scottish NMR laboratories through closer interdisciplinary collaboration, expertise sharing.
- guarantee access to the most suitable NMR equipment thus avoiding to need to duplicate specialised equipment in every laboratory. It therefore will have tangible economic benefits.
Our support for the NOMAD software package could provide a tipping point for its wider use in the NMR community and help the developers to realise their commercial ambitions. We strongly believe in this product, as it benefits all who come in contact with modern-day NMR laboratories: NMR personnel, NMR users and PIs. Their increase efficiencies, although difficult to put monetary value on at the moment, could be substantial.
In addition to everyday impact on the operation of NMR laboratories and the scientific outputs produced by their members, establishing the Scottish High Field NMR Centre will benefit numerous researchers who use NMR in their research and thus the impact they produce will be strengthen by the enhanced capability of our support.
As outlined in the Pathway to Impact, the important part of our impact strategy is a direct engagement with industry, SMEs in particular; we will facilitate the access to our equipment and expertise. We will thus directly contribute towards their economic success, strengthening their position in the competitive market and ultimately benefiting the UK economy.
Through our high-profile materials research we have engaged with international and local companies such as British Petroleum, Sasol and Cemex, contributing to the development of their products.
As many of our research themes are rooted in biological research, their ultimate impact will be in improved health and well-being of society. Examples of what we achieved in this area so far, are document in the Case for Support and include our engagement with Edinburgh Medical Imaging, Gemini Therapeutics, Invizius, or Ingenza.
Our environmental chemistry research will have impact on the quality of our environment and represents important societal impact.
Our coordinated efforts to educate future generations of NMR scientists and NMR users, will highly benefit their future careers, and thus contribute to their individual impact on the wealth and well-being of society. Our engagements with high-school students will encourage more to take part in this exciting and rewarding endeavour.
Organisations
- University of Edinburgh (Lead Research Organisation)
- UNIVERSITY OF EDINBURGH (Collaboration)
- Scotch Whisky Research Institute (Collaboration)
- UNIVERSITY OF GLASGOW (Collaboration)
- Heriot-Watt University (Collaboration)
- University of St Andrews (Collaboration)
- UNIVERSITY OF YORK (Collaboration)
- University of Bristol (Collaboration)
- Beatson Institute for Cancer Research (Collaboration)
Publications
Bell NGA
(2020)
Molecular level study of hot water extracted green tea buried in soils - a proxy for labile soil organic matter.
in Scientific reports
Bica R
(2022)
Methane emissions and rumen metabolite concentrations in cattle fed two different silages
in Scientific Reports
Bica R
(2020)
Nuclear Magnetic Resonance to Detect Rumen Metabolites Associated with Enteric Methane Emissions from Beef Cattle.
in Scientific reports
Brodaczewska N
(2018)
(3, 2)D 1H, 13C BIRDr,X-HSQC-TOCSY for NMR structure elucidation of mixtures: application to complex carbohydrates.
in Journal of biomolecular NMR
Davy M
(2022)
Monitoring off-resonance signals with SHARPER NMR - the MR-SHARPER experiment.
in The Analyst
De Cesare S
(2021)
Direct monitoring of biocatalytic deacetylation of amino acid substrates by 1H NMR reveals fine details of substrate specificity.
in Organic & biomolecular chemistry
Dickson CL
(2022)
SHARPER-enhanced benchtop NMR: improving SNR by removing couplings and approaching natural linewidths.
in Chemical communications (Cambridge, England)
Fraser HWL
(2018)
Order in disorder: solution and solid-state studies of [MM] wheels (MIII = Cr, Al; MII = Ni, Zn).
in Dalton transactions (Cambridge, England : 2003)
Hind C
(2022)
Insights into the Spectrum of Activity and Mechanism of Action of MGB-BP-3.
in ACS infectious diseases
Description | Notable achievement so far was the development of an NMR technique that doubles the sensitivity of direct mapping of the carbon skeleton of organic molecules. Using this methodology, carbon-carbon connectivity of organic molecules can, using the 800 MHz cryoprobe instrument funded by this award, be determined in an overnight experiment using single digit milligram amounts of a studied compound. The second developed methodology is termed SHARPER; it simplifies NMR signal and sharpens it, increasing the sensitivity of some NMR experiments between 10-100 fold. This brings considerable savings in spectrometer time or the material needed to measure spectra. SHRAPER is particularly suitable for reaction monitoring or quantifying diffusion of pure molecules. |
Exploitation Route | The SHARPER methodology can substantially improve sensitivity of NMR experiments. It therefore is of interest to a large audience of NMR spectroscopists working in academia and in industry. Particularly promising is its application on benchtop NMR instruments, as these mobile instruments can be placed in fume hoods and laboratories. From this point of view. this methodology is expected to find applications in industry, not only in the R&D, but also in the production lines. SHARPER methodology is widely applicable and we envisage that in the forthcoming years its numerous applications will emerge. |
Sectors | Agriculture Food and Drink Chemicals Environment |
URL | https://www.oxinst.com/blogs/oxford-instruments-panic-2022?utm_source=GM&utm_medium=email&utm_campaign=Blog+email_Feb+2023&utm_term=New+NMR+Blog+Alert&utm_content=66948&gator_td=m%2F4XUzpemfzO4TLVgojT6G5FGp1%2F8JOgSBMviFmzq35sfR61IvuQB6UUVPwvYuxAMEnNTAWrwDbrVdS9wHqGHoUwt1q64Gn8l18TdQK6bvcdmJ2yx3UPisP9Amxd73Q6kKqIauxplQx5GNgOz0rsB%2BKvCpC9DBpT1poyShO1HcoyOsIvt7ioOr9CF3ihAdHxF18vZ5%2BB2KpA3VfhfRt9%2BQ%3D%3D |
Description | 1. Resonance assignment of a 120 amino acid protein and its complexes for ALMAC (https://www.almacgroup.com/). The nature of the work is confidential is present and I cannot provide more details. 2. We have performed analysis of oxidation of methionines in a protein sequence for Ingenza (https://www.ingenza.com/). The nature of the work is confidential is present and I cannot provide more details. 3. Ongoing work for Penrhos Bio Ltd, https://penrhosbio.com/, a small biochemical start-up. The company is commercializing a Unilever licence to apply antimicrobial compounds for chemical defense against microbial contamination. Their target is to develop a sustainable solution to prevent formation of harmful biofilms. The nature of the work is confidential is present and I cannot provide more details. |
First Year Of Impact | 2019 |
Sector | Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | SHARPER NMR: fast and accurate analysis of molecules, reactions and processes |
Amount | £364,795 (GBP) |
Funding ID | EP/S016139/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2019 |
End | 11/2022 |
Description | Supporting 19F-centered NMR investigations across a range of biological applications |
Amount | £222,641 (GBP) |
Funding ID | BB/X019756/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 07/2023 |
End | 07/2024 |
Description | A Structural Study of Azide-Modified Bacterial Exopolysaccharide Slime by High-Field NMR Spectroscopy |
Organisation | University of Edinburgh |
Department | School of Biological Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided funding for spectrometer time and protein production |
Collaborator Contribution | Research lead, preparing carbohydrate |
Impact | In progress |
Start Year | 2019 |
Description | Adapting SHARPER for multiple frequencies |
Organisation | University of Bristol |
Department | School of Biochemistry Bristol |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The initial implementation of SHARPER for one NMR signal comes from my laboratory |
Collaborator Contribution | My partners are further developing the methodology to be applied to multiple signals |
Impact | The following publication resulted from this collaboration: https://doi.org/10.1039/D2AN00134A |
Start Year | 2019 |
Description | Characterisation of a fluoride-dependent riboswitch - elucidating the molecular basis of fluoride resistance in bacteria |
Organisation | University of St Andrews |
Department | School of Chemistry St Andrews |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided funding for spectrometer time purchase of DNA construct |
Collaborator Contribution | Research lead |
Impact | In progress |
Start Year | 2019 |
Description | DNA polymerase d |
Organisation | University of St Andrews |
Department | School of Biology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided funding for spectrometer time and protein production |
Collaborator Contribution | Research lead, preparing protein |
Impact | In progress |
Start Year | 2019 |
Description | Exploring the mechanism of asymmetric dimethyl arginine action on the calcium sensing receptor CaSR |
Organisation | University of Glasgow |
Department | Institute of Cardiovascular and Medical Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided funding for spectrometer time and protein production |
Collaborator Contribution | Research lead, preparing protein |
Impact | In progress |
Start Year | 2019 |
Description | Future Proofing Scotch Whisky, NMR spectroscopy to identify potential substitutes for peat in whisky production |
Organisation | Scotch Whisky Research Institute |
Country | United Kingdom |
Sector | Private |
PI Contribution | Research team: David Ellis, Ruaraidh McIntosh, Kacper Krakowiak (HWU), Nicholle Bell (U of Edinburgh) |
Collaborator Contribution | SWRI will produce whisky samples and characterise them using their standard methods. |
Impact | No outputs or outcomes yet. |
Start Year | 2022 |
Description | How does a novel targeting peptide direct proteins to mitochondria in response to oxidative stress? |
Organisation | University of Glasgow |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided funding for spectrometer time and protein production |
Collaborator Contribution | Research lead, preparing protein |
Impact | In progress |
Start Year | 2019 |
Description | Identification of Allosteric Sites in the Anti-Inflammatory Enzyme, EPAC1 |
Organisation | Heriot-Watt University |
Department | School of Engineering & Physical Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided funding for spectrometer time and protein production |
Collaborator Contribution | Research lead, preparing protein |
Impact | In progress |
Start Year | 2019 |
Description | Implementing SHARPER on benchtop NMR spectrometers |
Organisation | University of York |
Department | Department of Chemistry |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am the PI on the grant and brought the initial intellectual input into this collaboration. |
Collaborator Contribution | Expertise, initial training of staff, unfortunately interrupted by the pandemics. Access to benchtop NMR spectrometer, helping to optimise our experiments. |
Impact | Two publications resulted from this collaboration https://doi.org/10.1039/D2CC01325H https://doi.org/10.1021/acsmeasuresciau.2c00055 This collaboration assisted in obtaining a Horizon Europe grant to Dr Halse: Hyperpolarised portable NMR for targeted analytical solutions beyond the laboratory (HYPERSOL) (https://gtr.ukri.org/projects?ref=EP%2FX03528X%2F1) |
Start Year | 2020 |
Description | Investigating allosteric communication between the Cyclophilin and TPR domains of Cyp40 |
Organisation | University of Edinburgh |
Department | School of Biological Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided funding for spectrometer time and protein production |
Collaborator Contribution | Research lead , preparing protein |
Impact | In progress |
Start Year | 2019 |
Description | Investigating the relationship between tire performance and molecular dynamics |
Organisation | University of St Andrews |
Department | School of Chemistry St Andrews |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The team: David Ellis, David Bucknall, Ben Murphy (HWU) Knowledge of the research area, sample preparation |
Collaborator Contribution | Assistance with the acquisition of solid-state NMR spectra |
Impact | No outputs or outcomes yet |
Start Year | 2021 |
Description | Orthogonal SpyTag:SpyCatcher pairs |
Organisation | University of Edinburgh |
Department | Institute of Cell Biology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided funding for spectrometer time and protein production |
Collaborator Contribution | Research lead, preparing protein |
Impact | In progress |
Start Year | 2019 |
Description | Probing allosteric inhibition and activation of Acinetobacter baumannii ATP phosphoribosyltransferase |
Organisation | University of St Andrews |
Department | School of Biology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided funding for spectrometer time and protein production |
Collaborator Contribution | Research lead, preparing protein |
Impact | In progress |
Start Year | 2019 |
Description | Reconstituting a DNA repair complex |
Organisation | University of Edinburgh |
Department | School of Biological Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided funding for spectrometer time and protein production |
Collaborator Contribution | Research lead, preparing protein |
Impact | In progress |
Start Year | 2019 |
Description | Structure and dynamics of complement C2b variants aimed for use in lymphoma treatment |
Organisation | University of Edinburgh |
Department | School of Molecular Medicine Edinburgh |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided funding for spectrometer time and protein production |
Collaborator Contribution | Research lead, preparing protein |
Impact | In progress |
Start Year | 2019 |
Description | The use of SHARPER technique in the detection of ligand-macromolecule interactions |
Organisation | Beatson Institute for Cancer Research |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Transfer of the SHARPER methodology to be developed for drug screening. |
Collaborator Contribution | Testing of the methodology on model ligand-protein complexes. |
Impact | Early stage, no outputs yet. Expected publication: 2024 |
Start Year | 2022 |
Description | Loan of a benchtop NMR spectrometer to the Forth Valley College in Falkirk and associated NMR training |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Our 60 MHz NMR spectrometer was lent for 1 month (April/May 2018) to the Forth Valley College in Falkirk to be used in their chemistry classes. My student has trained teachers how to use the spectrometer. We have received a positive feedback. Experience working with the spectrometer deepened the interest in NMR spectroscopy to be potentially used in monitoring the production in chemical industry. |
Year(s) Of Engagement Activity | 2018 |