A Coordinated Infrastructure for NMR in the Physical and Life Sciences: Upgrade of the Leicester 800MHz NMR for Structural Biology and Drug Discovery
Lead Research Organisation:
University of Leicester
Department Name: Molecular and Cell Biology
Abstract
Nuclear Magnetic Resonance (NMR) spectroscopists from across the UK and working in a wide-range of research fields have agreed on a coordinated strategy for investment in very-high and ultra-high field NMR equipment. The results of this coordinated effort will provide for UK-wide access to new state-of-the-art capabilities, training and expertise in NMR technology for the physical and life sciences.
In Leicester, NMR underpins fundamental and applied science in a wide range of topics, including the understanding of the molecular mechanisms that establish the workings of biological macromolecular complexes in both normal and disease states and crucial research in structure-based drug discovery.
We request a contribution of Euro 967,894 (£887,946) from the research council, which combined with Euro 244,758 (£224,541; 20% overall matching) by the University of Leicester, will be used to upgrade our aged and technically obsolete 800 MHz NMR console and probe and expand its capability to include a flow system, direct 13C-detect, 15N-detect and solid-state capabilities. Together, these upgrades greatly enhance the ability to investigate challenging systems using integrated solution- and solid-state NMR approaches at the Leicester site, yielding significant advantages to structural biology for its local and external users.
Leicester will allow access via its strategic partner, the national NMR facility in Birmingham, and share technologically advanced methodologies, maximising the impact for the UK research, industry and society, thereby contributing to the UK economic viability and overall well-being.
Across the institutions of the UK-wide NMR infrastructure, we will work towards common mechanisms for access and reporting. An annual discussion forum will be established as part of this effort, to give all UK NMR spectroscopists, from academia and industry, and RCUK representatives, an opportunity to meet, to share best practice and confer on all relevant issues.
In Leicester, NMR underpins fundamental and applied science in a wide range of topics, including the understanding of the molecular mechanisms that establish the workings of biological macromolecular complexes in both normal and disease states and crucial research in structure-based drug discovery.
We request a contribution of Euro 967,894 (£887,946) from the research council, which combined with Euro 244,758 (£224,541; 20% overall matching) by the University of Leicester, will be used to upgrade our aged and technically obsolete 800 MHz NMR console and probe and expand its capability to include a flow system, direct 13C-detect, 15N-detect and solid-state capabilities. Together, these upgrades greatly enhance the ability to investigate challenging systems using integrated solution- and solid-state NMR approaches at the Leicester site, yielding significant advantages to structural biology for its local and external users.
Leicester will allow access via its strategic partner, the national NMR facility in Birmingham, and share technologically advanced methodologies, maximising the impact for the UK research, industry and society, thereby contributing to the UK economic viability and overall well-being.
Across the institutions of the UK-wide NMR infrastructure, we will work towards common mechanisms for access and reporting. An annual discussion forum will be established as part of this effort, to give all UK NMR spectroscopists, from academia and industry, and RCUK representatives, an opportunity to meet, to share best practice and confer on all relevant issues.
Planned Impact
Funding of this proposal, as part 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 UK industry, and greatly stimulate the education and training of the next generation of scientists.
The impact targets a number of areas:
1. To increase effectiveness, sharing and outputs through coordinated networking activities
The NMR community recognises the need and advantages of a single-point access portal, to provide relevant information about capacity, instrumentation, availability and scheduling, accounting, KPIs, as well as costs or other requirements for access. 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. A single-access portal would also be very advantageous for 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 NMR 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 UK science will be greatly enhanced.
3. To improve training and sharing of best practices
Suitable training of PhD and postgraduate researchers will create a source of expertise that underpins 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 access, engagement and outreach
The new capabilities in Leicester allow for the full range of state-of-the-art solution and/or solid-state resource intensive NMR projects. 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
Informing the general public is a key aspect in conveying the 'why and how' of scientific research, engaging the public with the need for the often costly scientific research, and arousing their curiosity in particular that of children of all ages, race and gender, as they are the scientists of the future.
The impact targets a number of areas:
1. To increase effectiveness, sharing and outputs through coordinated networking activities
The NMR community recognises the need and advantages of a single-point access portal, to provide relevant information about capacity, instrumentation, availability and scheduling, accounting, KPIs, as well as costs or other requirements for access. 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. A single-access portal would also be very advantageous for 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 NMR 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 UK science will be greatly enhanced.
3. To improve training and sharing of best practices
Suitable training of PhD and postgraduate researchers will create a source of expertise that underpins 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 access, engagement and outreach
The new capabilities in Leicester allow for the full range of state-of-the-art solution and/or solid-state resource intensive NMR projects. 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
Informing the general public is a key aspect in conveying the 'why and how' of scientific research, engaging the public with the need for the often costly scientific research, and arousing their curiosity in particular that of children of all ages, race and gender, as they are the scientists of the future.
Publications
Malki I
(2022)
Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity and cellular functions.
in Nucleic acids research
Mureddu LG
(2022)
Fragment-Based Drug Discovery by NMR. Where Are the Successes and Where can It Be Improved?
in Frontiers in molecular biosciences
Walker V
(2023)
Biochemistry and pathophysiology of the Transient Potential Receptor Vanilloid 6 (TRPV6) calcium channel.
in Advances in clinical chemistry
Description | The upgraded spectrometer is essential in providing state-of-the-art NMR experimental capabilities in Leicester. It supports both research and industrial R&D at the national and international level. |
Exploitation Route | Accessible resource for academia and industry. |
Sectors | Pharmaceuticals and Medical Biotechnology |
Description | Support and access to state-of-the-art experimental equipment for pharmaceutical industry. |
Sector | Pharmaceuticals and Medical Biotechnology |
Description | Novartis (partnership collaboration) |
Organisation | Novartis |
Department | Novartis Institutes for BioMedical Research Switzerland |
Country | Switzerland |
Sector | Private |
PI Contribution | We are currently engaging in a joint project to apply our tools and software expertise in NMR-based drug discovery to projects of direct interest to Novartis. We have regular project meetings to exchange knowledge and ideas and train their staff in the usage of the CcpNmr Analysis software platform for advanced NMR data analysis. |
Collaborator Contribution | License fees, in-kind contributions, data, expertise |
Impact | Proper translational research and the access to state-of-the-art technologies by pharmaceutical industry is key to maintaining and reinforcing an advanced technological industrial base and reinforces the UK desire to be at the forefront of biomedical research. |
Start Year | 2021 |
Description | connectNMR 2019 |
Organisation | University of Liverpool |
Department | School of Life Sciences Liverpool |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | A newly emerged effort to coordinate NMR activities across the UK, to promote sharing, knowledge exchange, and access to NMR research infrastructure equipment. |
Collaborator Contribution | We constitute one of the funded sides and as CCPN function as a key partner in the effort. |
Impact | NA |
Start Year | 2018 |
Title | CcpNmr AnalysisAssign version 3.0.4 |
Description | Premier software package with unique capabilities for liquid-state and solid-state NMR data analysis.New releases for Mac OSX, Linux and Windows. |
Type Of Technology | Software |
Year Produced | 2021 |
Open Source License? | Yes |
Impact | All CcpNmr packages jointly cited >2200 times. |
URL | https://ccpn.ac.uk |
Title | CcpNmr AnalysisAssign, release 3.1.0 |
Description | Premier NMR software package with unique capabilities for liquid-state and solid-state NMR data analysis. New releases for Mac OSX, Linux and Windows. |
Type Of Technology | Software |
Year Produced | 2022 |
Open Source License? | Yes |
Impact | All CcpNmr packages jointly cited >2300 times. CcpNmr programme suite now used by 23 bioPharma companies. |
Title | CcpNmr AnalysisAssign, releases 3.0.3 |
Description | Premier software package with unique capabilities for liquid-state and solid-state NMR data analysis.New releases for Mac OSX, Linux and Windows. |
Type Of Technology | Software |
Year Produced | 2021 |
Open Source License? | Yes |
Impact | All CcpNmr packages jointly cited >2200 times. |
URL | https://ccpn.ac.uk |
Title | CcpNmr AnalysisMetabolomics version 3.0-alfa1 |
Description | CcpNmr AnalysisMetabolomics alfa1 for NMR metabolomics data analysis and visualisation. |
Type Of Technology | Software |
Year Produced | 2018 |
Impact | N/A |
Title | CcpNmr AnalysisMetabolomics, releases 3.0.3 and 3.0.4 |
Description | Premier software package with unique capabilities for liquid-state and solid-state NMR data analysis with a focus on NMR metabolomics. New releases for Mac OSX, Linux and Windows. |
Type Of Technology | Software |
Year Produced | 2021 |
Open Source License? | Yes |
Impact | All CcpNmr packages jointly cited >2200 times |
URL | https://ccpn.ac.uk |
Title | CcpNmr AnalysisScreen versions 3.0-beta1, beta2 (2018) |
Description | Beta1 and Beta2 releases of AnalysisScreen; a dedicated programme for the analysis of NMR screening data |
Type Of Technology | Software |
Year Produced | 2018 |
Impact | The programme was used for a thorough and systematic analysis of NMR-based screening protocols. Papers describing the programme and this analysis are currently ion preparation. |
Title | CcpNmr AnalysisScreen, release 3.1.0 |
Description | Premier NMR software package with unique capabilities for NMR-based fragment-based drug discovery. New releases for Mac OSX, Linux and Windows. |
Type Of Technology | Software |
Year Produced | 2022 |
Open Source License? | Yes |
Impact | All CcpNmr packages jointly cited >2300 times. CcpNmr programme suite now used by 23 bioPharma companies. |
Title | CcpNmr AnalysisScreen, releases 3.0.3 and 3.0.4 |
Description | Premier software package with unique capabilities for liquid-state and solid-state NMR data analysis with a focus on NMR-base small molecule screening. New releases for Mac OSX, Linux and Windows. |
Type Of Technology | Software |
Year Produced | 2021 |
Open Source License? | Yes |
Impact | All CcpNmr packages jointly cited >2200 times. |
URL | https://ccpn.ac.uk |
Title | CcpNmr AnalysisStructure, release 3.0.4 |
Description | remier software package with unique capabilities for liquid-state and solid-state NMR data analysis with a focus on NMR structure generation and validation. New releases for Mac OSX, Linux and Windows. |
Type Of Technology | Software |
Year Produced | 2021 |
Open Source License? | Yes |
Impact | All CcpNmr packages jointly cited >2200 times. |
URL | https://ccpn.ac.uk |
Description | Connect-NMR Dynamics Workshop, Leicester, June 2023 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | The CCPN workshops, roadshow and training events provide for hand-on instruction and trainings, as well as dedicated Q&A sessions. Thus, they serve important roles in direct interaction with our user base, providing training and expertise sharing. This workshop was specifically designed to integrate the activities of CONNECT-NMR with CCPN. Knowledge sharing, training and collaborative efforts constitute one of the core deliverables of the CCPN project. |
Year(s) Of Engagement Activity | 2023 |
URL | https://ccpn.ac.uk/outreach/workshops/ |