The Scottish Macromolecular Imaging Centre (SMIC)
Lead Research Organisation:
University of Glasgow
Department Name: UNLISTED
Abstract
To understand the processes of life and disease, it is important to understand the shapes of biological molecules. Watson and Crick's ground-breaking work to understand the structure of DNA revolutionised our knowledge of the mechanisms by which traits are passed from parent to child in the form of genes.
Scotland has a thriving community of structural biologists engaged in research to understand the shapes of protein and DNA molecules, their interactions and functions. A powerful new technique has emerged in the past few years; cryogenic electron microscopy (CryoEM). This allows scientists to record images of assemblies, such as viruses or enzymes - the molecular machines that perform vital tasks within the cell. These images can be processed in the computer to determine the structure
of the objects at the atomic level. These structures then inform our understanding of how biological processes occur.
The Scottish Macromolecular Imaging Centre is a world-class cryoEM research facility, founded by a partnership of Scottish Universities - Glasgow, Edinburgh, Dundee and St. Andrews. It acts as a hub for a network of expert scientists, fostering new collaborations and training programmes to ensure scientific excellence and a new generation of highly skilled young structural biologists."
Scotland has a thriving community of structural biologists engaged in research to understand the shapes of protein and DNA molecules, their interactions and functions. A powerful new technique has emerged in the past few years; cryogenic electron microscopy (CryoEM). This allows scientists to record images of assemblies, such as viruses or enzymes - the molecular machines that perform vital tasks within the cell. These images can be processed in the computer to determine the structure
of the objects at the atomic level. These structures then inform our understanding of how biological processes occur.
The Scottish Macromolecular Imaging Centre is a world-class cryoEM research facility, founded by a partnership of Scottish Universities - Glasgow, Edinburgh, Dundee and St. Andrews. It acts as a hub for a network of expert scientists, fostering new collaborations and training programmes to ensure scientific excellence and a new generation of highly skilled young structural biologists."
Technical Summary
Cryogenic transmission electron microscopy is revolutionising the field of structural biology, allowing researchers to determine rapidly the structures of macromolecular assemblies at close to atomic resolution. Furthermore, developments in cryogenic imaging of the cell are beginning to realise the exciting prospect of in-situ structure determination.
We propose to establish a world-class centre for CryoEM with the primary objective of supporting macromolecular structure determination for life-science researchers in Scotland and northern England. Based in the Medical Research Council - University of Glasgow Centre for Virus Research (CVR), the Scottish Macromolecular Imaging Centre (SMIC) will be equipped with a 300 keV automated cryo-transmission electron microscope that is fitted with a direct electron detection camera, an energy filter and phase plates for high-contrast imaging. The centre will be founded by a consortium of Scottish Universities and serve as the hub for a network of structural biology researchers, fostering collaborations, training programmes and mutual support. Existing cryoEM resources at Glasgow, Dundee and Edinburgh will act as feeder sites with expert technical support to facilitate project development before presentation at SMIC. Oversight of SMIC by a management group will ensure that highest quality outputs are achieved and that the facility is operated with maximum efficiency.
We propose to establish a world-class centre for CryoEM with the primary objective of supporting macromolecular structure determination for life-science researchers in Scotland and northern England. Based in the Medical Research Council - University of Glasgow Centre for Virus Research (CVR), the Scottish Macromolecular Imaging Centre (SMIC) will be equipped with a 300 keV automated cryo-transmission electron microscope that is fitted with a direct electron detection camera, an energy filter and phase plates for high-contrast imaging. The centre will be founded by a consortium of Scottish Universities and serve as the hub for a network of structural biology researchers, fostering collaborations, training programmes and mutual support. Existing cryoEM resources at Glasgow, Dundee and Edinburgh will act as feeder sites with expert technical support to facilitate project development before presentation at SMIC. Oversight of SMIC by a management group will ensure that highest quality outputs are achieved and that the facility is operated with maximum efficiency.
Organisations
- University of Glasgow (Lead Research Organisation)
- UNIVERSITY OF EDINBURGH (Collaboration)
- UNIVERSITY OF LEICESTER (Collaboration)
- University of St Andrews (Collaboration)
- Birkbeck, University of London (Collaboration)
- UNIVERSITY OF LEEDS (Collaboration)
- DIAMOND LIGHT SOURCE (Collaboration)
- UNIVERSITY OF DUNDEE (Collaboration)
People |
ORCID iD |
David Bhella (Principal Investigator) |
Publications
Bhella D
(2019)
Cryo-electron microscopy: an introduction to the technique, and considerations when working to establish a national facility.
in Biophysical reviews
Cannone G
(2023)
Structure of the Saccharolobus solfataricus type III-D CRISPR effector.
in Current research in structural biology
Dell M
(2024)
Trapping of a Polyketide Synthase Module after C-C Bond Formation Reveals Transient Acyl Carrier Domain Interactions.
in Angewandte Chemie (International ed. in English)
Haney J
(2022)
Coinfection by influenza A virus and respiratory syncytial virus produces hybrid virus particles.
in Nature microbiology
Hogrel G
(2022)
Cyclic nucleotide-induced helical structure activates a TIR immune effector.
in Nature
Lemonidis K
(2022)
Structural and biochemical basis of interdependent FANCI-FANCD2 ubiquitination
in The EMBO Journal
Maib H
(2022)
A mechanism for exocyst-mediated tethering via Arf6 and PIP5K1C-driven phosphoinositide conversion
in Current Biology
Description | A community based training programme for cryo-electron microscopy |
Amount | £500,000 (GBP) |
Funding ID | 218785/Z/19/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2021 |
End | 03/2026 |
Description | Accelerating throughput at Scotland's national Cryo-EM centre - a next generation direct electron detector for SCMI |
Amount | £239,700 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2022 |
End | 03/2023 |
Description | Cryo-Electron Microscopy Research Infrastructure - The Scottish Macromolecular Imaging Centre (SMIC). |
Amount | £60,000 (GBP) |
Organisation | Scottish Universities Life Sciences Alliance |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2017 |
End | 08/2022 |
Description | Cryo-Electron Microscopy Research Infrastructure - The Scottish Macromolecular Imaging Centre (SMIC). |
Amount | £100,000 (GBP) |
Organisation | Government of Scotland |
Department | Scottish Funding Council |
Sector | Public |
Country | United Kingdom |
Start | 07/2017 |
End | 08/2022 |
Description | MRC Equipment competitive opportunity: A 120 keV cryo-transmission electron microscope |
Amount | £200,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2022 |
End | 03/2023 |
Description | Molecular basis for Rift Valley fever phlebovirus NSs protein function |
Amount | £813,016 (GBP) |
Funding ID | MR/W018608/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2022 |
End | 07/2025 |
Description | Structural characterisation of the calicivirus entry pathway and its role in defining virulence |
Amount | £848,091 (GBP) |
Funding ID | BB/T002239/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2020 |
End | 12/2024 |
Description | World Class Laboratories - A disaster recovery system for the Scottish Centre for Macromolecular Imaging |
Amount | £404,391 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2023 |
End | 03/2023 |
Title | Cryo-EM structure of Lumazine Synthase |
Description | Cryo-EM dataset |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | None |
Title | Cryo-electron tomogram of a pseudotype virus particle generated during coinfection of Influenza A virus and Respiratory Syncytial virus in lung cells. |
Description | Tomogram produced by cryo-electron tomography of cells infected with respiratory syncytial virus and influenza A virus. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | Published in Nature communications https://doi.org/10.1038/s41564-022-01242-5 |
URL | https://www.ebi.ac.uk/emdb/EMD-13228 |
Title | Reconstituted USP1, UAF1, FANCI, and mono-ubiquitinated FANCD2 |
Description | Cryo-EM images of protein complex |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | Published in Nature Structural and Molecular Biology |
URL | https://www.ebi.ac.uk/empiar/EMPIAR-11305/ |
Title | The cryo-EM structure of vesivirus 2117 highlights functional variations in entry pathways for viruses in different clades of the vesivirus genus. |
Description | Cryo-EM image dataset |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | None |
Title | Tobacco mosaic virus, imaged on a JEOL CRYOARM 300 and Direct Electron Apollo |
Description | A very high resolution cryo-EM dataset of tobacco mosaic virus. The data were processed to 1.85 angstroms resolution |
Type Of Material | Database/Collection of data |
Year Produced | 2023 |
Provided To Others? | Yes |
Impact | highlighted by EMPIAR and EMDB as highest resolution helical reconstruction deposited to date. |
URL | https://www.ebi.ac.uk/empiar/EMPIAR-11404/ |
Title | Ubiquitinated FANCI in complex with FANCD2 and double-stranded DNA |
Description | Cryo-EM images of protein complex |
Type Of Material | Database/Collection of data |
Year Produced | 2023 |
Provided To Others? | Yes |
Impact | Published in EMBO J https://dx.doi.org/doi:10.15252/embj.2022111898 |
URL | https://www.ebi.ac.uk/empiar/EMPIAR-11372/ |
Title | cA3-bound TIR-SAVED |
Description | Cryo-electron micrographs of TIR_SAVED protein bound to cA3. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | The micrographs were processed into 3D structures, deposited as EMDB-14122 and PDB-7QQK. The paper containing this data and the resulting structures was published in Nature. |
Description | Scottish Centre for Macromolecular Imaging |
Organisation | University of Dundee |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Consortium partners contributed financially to the establishment of SCMI and agree to subscribe to the centre on an annual fee for access basis. |
Collaborator Contribution | The partners are users of the national cryo-EM facility SCMI |
Impact | We have established a national centre for structural biology research by cryo-EM |
Start Year | 2018 |
Description | Scottish Centre for Macromolecular Imaging |
Organisation | University of Edinburgh |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Consortium partners contributed financially to the establishment of SCMI and agree to subscribe to the centre on an annual fee for access basis. |
Collaborator Contribution | The partners are users of the national cryo-EM facility SCMI |
Impact | We have established a national centre for structural biology research by cryo-EM |
Start Year | 2018 |
Description | Scottish Centre for Macromolecular Imaging |
Organisation | University of St Andrews |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Consortium partners contributed financially to the establishment of SCMI and agree to subscribe to the centre on an annual fee for access basis. |
Collaborator Contribution | The partners are users of the national cryo-EM facility SCMI |
Impact | We have established a national centre for structural biology research by cryo-EM |
Start Year | 2018 |
Description | Wellcome/MRC training programme in cryo-EM |
Organisation | Birkbeck, University of London |
Department | Institute of Structural and Molecular Biology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Developed lecture materials and acted as course tutor on training course. In future, SCMI will host courses using our microscopes and equipment. Take part in management group meetings to steer the overall project and course portfolio. |
Collaborator Contribution | Leeds - overall management of project, host and delivered courses. eBIC - host and delivered courses Birkbeck - taught on courses Leicester - host and deliver courses |
Impact | Delivery of 6 training courses targetting researchers with different skill levels in cryo-EM. |
Start Year | 2021 |
Description | Wellcome/MRC training programme in cryo-EM |
Organisation | Diamond Light Source |
Country | United Kingdom |
Sector | Private |
PI Contribution | Developed lecture materials and acted as course tutor on training course. In future, SCMI will host courses using our microscopes and equipment. Take part in management group meetings to steer the overall project and course portfolio. |
Collaborator Contribution | Leeds - overall management of project, host and delivered courses. eBIC - host and delivered courses Birkbeck - taught on courses Leicester - host and deliver courses |
Impact | Delivery of 6 training courses targetting researchers with different skill levels in cryo-EM. |
Start Year | 2021 |
Description | Wellcome/MRC training programme in cryo-EM |
Organisation | University of Leeds |
Department | Astbury Biostructure Laboratory |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Developed lecture materials and acted as course tutor on training course. In future, SCMI will host courses using our microscopes and equipment. Take part in management group meetings to steer the overall project and course portfolio. |
Collaborator Contribution | Leeds - overall management of project, host and delivered courses. eBIC - host and delivered courses Birkbeck - taught on courses Leicester - host and deliver courses |
Impact | Delivery of 6 training courses targetting researchers with different skill levels in cryo-EM. |
Start Year | 2021 |
Description | Wellcome/MRC training programme in cryo-EM |
Organisation | University of Leicester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Developed lecture materials and acted as course tutor on training course. In future, SCMI will host courses using our microscopes and equipment. Take part in management group meetings to steer the overall project and course portfolio. |
Collaborator Contribution | Leeds - overall management of project, host and delivered courses. eBIC - host and delivered courses Birkbeck - taught on courses Leicester - host and deliver courses |
Impact | Delivery of 6 training courses targetting researchers with different skill levels in cryo-EM. |
Start Year | 2021 |