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."

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.

People

ORCID iD

Publications

10 25 50
 
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 04/2021 
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 08/2017 
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 08/2017 
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 07/2022 
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 12/2022
 
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/
 
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