A Midlands Regional Cryo-EM facility
Lead Research Organisation:
University of Leicester
Department Name: UNLISTED
Abstract
Human cells are full of large protein assemblies that act as molecular machines to carry out the functions of the cell. These include machines that carry out metabolism; that regulate our genetic material; that manage the process of cell division; and finally the machines that make the machines themselves.
Structural biologists seek to determine the structure and function of these machines. Through this, we not only gain an understanding of the mechanisms that underpin life, but also learn how to develop novel approaches to cure disease. The traditional techniques of structural biology have proven insufficient when studying large molecular assemblies. Recently, a breakthrough in new cameras and powerful computation has made it possible to use electron microscopy to determine the
architectures of these machines. This circumvents the limitations of traditional methods and represents a revolution in structural biology.
We are applying for a high-end cryo-electron microscope to be operated as a regional facility. We have a very strong network of partners in the Midlands whose research will be transformed by the new instrument. This will enable a detailed mechanistic understanding of many of the important processes of life including gene expression, DNA replication and repair, cellular organisation and communication.
Structural biologists seek to determine the structure and function of these machines. Through this, we not only gain an understanding of the mechanisms that underpin life, but also learn how to develop novel approaches to cure disease. The traditional techniques of structural biology have proven insufficient when studying large molecular assemblies. Recently, a breakthrough in new cameras and powerful computation has made it possible to use electron microscopy to determine the
architectures of these machines. This circumvents the limitations of traditional methods and represents a revolution in structural biology.
We are applying for a high-end cryo-electron microscope to be operated as a regional facility. We have a very strong network of partners in the Midlands whose research will be transformed by the new instrument. This will enable a detailed mechanistic understanding of many of the important processes of life including gene expression, DNA replication and repair, cellular organisation and communication.
Technical Summary
We are seeking to establish a regional cryo-Electron Microscopy facility in the Midlands. This will serve the needs of a large community of structural and cell biologists, enabling them to take advantage of the revolution in this technology. The facility will comprise a high-end 300kV instrument in Leicester and a 200kV feeder instrument in Warwick. Together with existing feeder instruments, this will establish an ecosystem (with both shared equipment, expertise and training) that will transform structural biology in the Midlands.
The facility will support the research of more than 37 researchers studying complexes involved in gene regulation, DNA replication and repair, cellular organisation and communication. In addition, we will use the instrument to develop methods for time resolved cryo-EM and imaging membrane proteins using SMALP technology.
In recognition of the strategic value of this facility, the regional Institutions have together committed to making a substantial financial contribution (>40%). There is a strong track record of collaboration and expertise sharing between the Midlands structural biologists. This will ensure effective use of the facility, accelerating our world-class research into the structure and mechanism of the molecular machinery that drives cellular function.
The facility will support the research of more than 37 researchers studying complexes involved in gene regulation, DNA replication and repair, cellular organisation and communication. In addition, we will use the instrument to develop methods for time resolved cryo-EM and imaging membrane proteins using SMALP technology.
In recognition of the strategic value of this facility, the regional Institutions have together committed to making a substantial financial contribution (>40%). There is a strong track record of collaboration and expertise sharing between the Midlands structural biologists. This will ensure effective use of the facility, accelerating our world-class research into the structure and mechanism of the molecular machinery that drives cellular function.
People |
ORCID iD |
John Schwabe (Principal Investigator) |
Publications
![publication icon](/resources/img/placeholder-60x60.png)
Ball LE
(2021)
Influence of DIBMA Polymer Length on Lipid Nanodisc Formation and Membrane Protein Extraction.
in Biomacromolecules
![publication icon](/resources/img/placeholder-60x60.png)
Bate N
(2022)
In vitro evolution predicts emerging SARS-CoV-2 mutations with high affinity for ACE2 and cross-species binding.
in PLoS pathogens
![publication icon](/resources/img/placeholder-60x60.png)
Blair K
(2022)
Mechanism of human Lig1 regulation by PCNA in Okazaki fragment sealing.
in Nature communications
![publication icon](/resources/img/placeholder-60x60.png)
Brotherton DH
(2022)
Conformational changes and CO2-induced channel gating in connexin26.
in Structure (London, England : 1993)
![publication icon](/resources/img/placeholder-60x60.png)
Carter J
(2021)
Linear Dichroism Activity of Chiral Poly( p -Aryltriazole) Foldamers
in ACS Omega
![publication icon](/resources/img/placeholder-60x60.png)
Chi G
(2022)
Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain.
in Nature communications
![publication icon](/resources/img/placeholder-60x60.png)
Chi G
(2021)
Phospho-regulation, nucleotide binding and ion access control in potassium-chloride cotransporters.
in The EMBO journal
![publication icon](/resources/img/placeholder-60x60.png)
Concilio M
(2023)
Mechanism of Action of Oxazoline-Based Antimicrobial Polymers Against Staphylococcus aureus: In Vivo Antimicrobial Activity Evaluation.
in Advanced healthcare materials
![publication icon](/resources/img/placeholder-60x60.png)
Falcon B
(2019)
Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules.
in Nature
![publication icon](/resources/img/placeholder-60x60.png)
Figley MD
(2021)
SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration
in Neuron
Description | A community based training programme for cryo-electron microscopy |
Amount | £1,000,000 (GBP) |
Funding ID | 218785/Z/19/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2021 |
End | 02/2026 |
Title | Assembly of the asymmetric human ?-tubulin ring complex by RUVBL1-RUVBL2 AAA ATPase |
Description | Cryo-EM map of RUVBL1-RUVBL2 |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | This study solves the structure of the RUVBL1 and RUVBL2 by Cryo-EM and finds that RUVBL as an assembly factor that regulates ?TuRC in cells and allows production of recombinant ?TuRC for future in-depth mechanistic studies. |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-11888 |
Title | Cohesin complex with loader gripping DNA |
Description | Cryo-EM map of the cohesin complex with loader gripping DNA |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | Fundamental understanding of Cohesin mediated DNA attachement. |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-10930 |
Title | Cryo EM map of BS3 crosslinked CoREST complex (LSD1:RCOR1:HDAC1) - open form |
Description | 21.5 Å Cryo EM map of BS3 crosslinked CoREST complex (LSD1:RCOR1:HDAC1) - open form |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the interaction of LSD1, RCOR1 and HDAC1 in the CoREST deacetylase complex |
URL | https://www.emdataresource.org/EMD-10629 |
Title | Cryo EM map of BS3 crosslinked CoREST complex (LSD1:RCOR1:HDAC1)- closed form |
Description | 20 Å Cryo EM map of BS3 crosslinked CoREST complex (LSD1:RCOR1:HDAC1)- closed form |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the interaction of LSD1, RCOR1 and HDAC1 in the CoREST deacetylase complex. |
URL | https://www.emdataresource.org/EMD-10628 |
Title | Cryo-EM map of glutaraldehye cross-linked CoREST complex (LSD1:RCOR1:HDAC1) |
Description | 17.5 Å cryo-EM map of glutaraldehye cross-linked CoREST complex (LSD1:RCOR1:HDAC1) |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the interaction of LSD1, RCOR1 and HDAC1 in the CoREST deacetylase complex. |
URL | https://www.emdataresource.org/EMD-10627 |
Title | Cryo-EM structure of human Pol ? bound to DNA and mono-ubiquitylated PCNA |
Description | Cryo-EM structure of human Pol ? bound to DNA and mono-ubiquitylated PCNA |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | The data provide a structural basis for the recruitment of a Y-family TLS polymerase to sites of DNA damage. |
URL | https://www.ebi.ac.uk/empiar/EMPIAR-10933/ |
Title | CryoEM analysis of ternary complex of full-length Caspase-8 with FADD and FLIPs |
Description | Cryo-EM map of full-length Caspase-8 |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Cryo-EM structural analysis of FADD:Caspase-8 complexes defines the catalytic dimer architecture for co-ordinated control of cell fate. |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-11941 |
Title | EM map CoREST complex with a nucleosome with 185 bp 601 sequence DNA and a propargylamine mimic of dimethy Lys4 histone H3 |
Description | 26.1 Å map of the CoREST complex with a nucleosome with 185 bp 601 sequence DNA and a propargylamine mimic of dimethy Lys4 histone H3 |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the interaction of the CoREST complex with a nucleosome with 185 bp 601 sequence DNA and a propargylamine mimic of dimethy Lys4 histone H3 |
URL | https://www.emdataresource.org/EMD-10630 |
Title | EM map of of the core MTA1/HDAC1/MBD2 NURD deacetylase complex |
Description | 6.1 Å structure of the core MTA1/HDAC1/MBD2 NURD deacetylase complex |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the topology of chromatin-binding domains in the NuRD deacetylase complex. |
URL | https://www.emdataresource.org/EMD-11838 |
Title | EM map of the MTA1/HDAC1/MBD2 NURD deacetylase complex |
Description | 4.5 Å structure of the MTA1/HDAC1/MBD2 NURD deacetylase complex solved by cryo-electron microscopy |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the topology of chromatin-binding domains in the NuRD deacetylase complex. |
URL | https://www.emdataresource.org/EMD-11837 |
Title | EM map of the dimeric HDAC1/MIDEAS/DNTTIP1 MiDAC deacetylase complex |
Description | 4.0 Å EM map of the dimeric HDAC1/MIDEAS/DNTTIP1 MiDAC deacetylase complex |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the interaction of HDAC1, MIDEA and DNTTIP1 in the dimeric MiDAC deacetylase complex |
URL | https://www.emdataresource.org/EMD-11041 |
Title | EM map of the extended MTA1/HDAC1/MBD2/RBBP4 NURD deacetylase complex |
Description | 19.4 Å EM map of the extended MTA1/HDAC1/MBD2/RBBP4 NURD deacetylase complex |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the topology of chromatin-binding domains in the NuRD histone deacetylase complex |
URL | https://www.emdataresource.org/EMD-11839 |
Title | EM map of the tetrameric HDAC1/MIDEAS/DNTTIP1 MiDAC deacetylase complex |
Description | 4.5 Å map of the tetrameric HDAC1/MIDEAS/DNTTIP1 MiDAC deacetylase complex solved by electron microscopy |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the interaction of HDAC1, MIDEAS and DNTTIP1 in the tetrameric MiDAC deacetylase complex |
URL | https://www.emdataresource.org/EMD-11042 |
Title | EMD-13416 |
Description | Human voltage-gated potassium channel Kv3.1 (apo condition) |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | Model from paper "Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain" |
URL | https://www.ebi.ac.uk/emdb/EMD-13416 |
Title | EMD-14971 |
Description | Cryo-EM structure of the indirubin-bound Hsp90-XAP2-AHR complex |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | EM structure from "Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex." |
URL | https://www.ebi.ac.uk/emdb/EMD-14971 |
Title | EMD-24273 |
Description | Cryo-EM structure of activated human SARM1 in complex with NMN and 1AD (ARM and SAM domains) |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | EM map from "Structural basis of SARM1 activation, substrate recognition, and inhibition by small molecules." |
URL | https://www.ebi.ac.uk/emdb/EMD-24273 |
Title | Human Phenylalanine Hydroxylase (hPAH) apo structure |
Description | Cryo-EM map of Human Phenylalanine Hydroxylase |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | Phenylalanine hydroxylase (PAH) is a key enzyme in the catabolism of phenylalanine, and mutations in this enzyme cause phenylketonuria (PKU), a genetic disorder that leads to brain damage and mental retardation if untreated. Its structure allows the understanding of the molecular mechanisms of action. |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-4605 |
Title | Multi-modal adaptor-clathrin contacts drive coated vesicle assembly |
Description | Multi-modal adaptor-clathrin contacts drive coated vesicle assembly |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Analysis the cryo-EM structure of clathrin cages assembled in the presence of ß2 hinge-appendage (ß2HA). |
URL | https://www.ebi.ac.uk/empiar/EMPIAR-10783/ |
Title | Negative stain map of CoREST complex (LSD1:RCOR1:HDAC1) |
Description | 17.5 Å negative stain map of CoREST complex (LSD1:RCOR1:HDAC1) solved by electron microscopy |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the interaction of LSD1, RCOR1 and HDAC1 in the CoREST deacetylase complex. |
URL | https://www.emdataresource.org/EMD-10626 |
Title | Phospho-regulation, nucleotide binding and ion access control in potassium-chloride cotransporters |
Description | Structure of Wild-Type Human Potassium Chloride Transporter KCC3 in NaCl |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | These study provides fundamentally new insights into the complex regulation of KCCs and may unlock innovative strategies for drug development. |
URL | https://www.ebi.ac.uk/emdb/EMD-12311 |
Title | SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration |
Description | Cryo-EM structure of ligand-free Human SARM1 |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Using structural, biochemical, biophysical, and cellular assays, this study demonstrated that SARM1 is activated by an increase in the ratio of NMN to NAD+ and show that both metabolites compete for binding to the auto-inhibitory N-terminal armadillo repeat (ARM) domain of SARM1 and showed that NMN influences the structure of SARM1. |
URL | https://www.ebi.ac.uk/emdb/EMD-23278 |
Title | Structure of beta-Galactosidase from Thermotoga maritima |
Description | Cryo-EM map of beta-galactosidase from Thermotoga maritima |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | The study provides a basis for the rational design of hybrid enzymes that can be efficiently attached to different solid supports. |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-10109 |
Title | Structure of the MTA1/HDAC1/MBD2 NURD deacetylase complex |
Description | 4.5 Å structure of the MTA1/HDAC1/MBD2 NURD deacetylase complex solved by cryo-electron microscopy. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the topology of chromatin-binding domains in the NuRD deacetylase complex. |
URL | https://www.rcsb.org/structure/7AO8 |
Title | Structure of the core MTA1/HDAC1/MBD2 NURD deacetylase complex |
Description | 6.1 Å structure of the core MTA1/HDAC1/MBD2 NURD deacetylase complex solved by cry-electron microscopy |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the topology of chromatin-binding domains in the NuRD deacetylase complex. |
URL | https://www.rcsb.org/structure/7AO9 |
Title | Structure of the extended MTA1/HDAC1/MBD2/RBBP4 NURD deacetylase complex |
Description | 19.4 Å structure of the extended MTA1/HDAC1/MBD2/RBBP4 NURD deacetylase complex solved by cry-electron microscopy |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the the topology of chromatin-binding domains in the NuRD deacetylase complex. |
URL | https://www.rcsb.org/structure/7AOA |
Title | Structure of the processive human Pol d holoenzyme |
Description | Cryo-EM map of the processive human polymerase delta holoenzyme |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | understanding on the function and assembly of the human Okazaki fragment polymerase |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-10539 |
Title | The pore structure of Clostridium perfringens epsilon toxin |
Description | Cryo-EM map of Epsilon Toxin |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | Understanding the molecular mechanism of Epsilon toxin structure and membrane insertion |
URL | https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-4789 |
Title | The structure of the dimeric HDAC1/MIDEAS/DNTTIP1 MiDAC deacetylase complex |
Description | 4.0 Å structure of the dimeric HDAC1/MIDEAS/DNTTIP1 MiDAC deacetylase complex |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the interaction of HDAC1, MIDEAS and DNTTIP1 in the MiDAC deacetylase complex |
URL | https://www.rcsb.org/structure/6Z2J |
Title | The structure of the tetrameric HDAC1/MIDEAS/DNTTIP1 MiDAC deacetylase complex |
Description | 4.5 Å structure of the tetrameric HDAC1/MIDEAS/DNTTIP1 MiDAC deacetylase complex solved by cryo-electron microscopy |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | An understanding of the interactions between HDAC1, DNTTIP1 and MIDEAS in the mIDAC histone deacetylase complex |
URL | https://www.rcsb.org/structure/6Z2K |
Description | Midlands Regional Partners using the Cryo-EM Facility-Update |
Organisation | University of Birmingham |
Department | Birmingham 1000 Elders Group |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The Midlands Regional Cryo-EM Facility was setup to serve the expanding Cryo-EM needs of the Midlands. The university of Leicester has provided the facilities to accommodate the Titan Krios microscope and employs a facility manager to run this facility. In addition, a high performance computer cluster was setup with a dedicated manager that allows data collected from the microscope to be processed on-site leading to high resolution 3D structures. The regional partners have access in the form of 20 days per year for data collection for a period of 5 years commencing in 2018. In addition all partners can process their data on the high performance cluster. The university of Leicester facility managers are also responsible for training of new users from the Midlands in specimen preparation, data collection and data processing. In addition Leicester offers an annual Midlands Cryo-EM workshop where 4 participants from each partner university can attend and learn the basics of Cryo-EM. In 2021 the workshop was conducted entirely online and included lectures from experts in the field and a hand-on image processing tutorial. In addition to the workshop, online tutorials for data collection have also taken place benefitting not only our Midlands partners but also external users from the UK and Europe that make use of the Midlands facilities. Lecture videos and slides have been made available to the Midlands community via our website (https://le.ac.uk/liscb/facilities-and-technologies/cryo-electron-microscopy/guides-and-learning-resources). Finally a weekly Data Processing Club is held online to discuss data processing, microscopy or developments in the field. |
Collaborator Contribution | Each regional partner has contributed £200,000 to the cost of setting up the facility. In addition the university of Warwick serves as the screening hub for projects to build up before collecting data at Leicester. The regional partners are using the facility on high impact projects that will lead to high-quality publications. |
Impact | To date over 70 high-resolution structures of biological macromolecules have been determined using the Midlands Titan Krios (Including industry user structures which will not be published). To this date there have been 16 publications in total of which 9 are from Midlands universities. Several more have been submitted for review and/or submitted to pre-print servers. A total of 25 groups from the four Midlands Universities are now involved in Cryo-EM projects of which only 6 were involved in Cryo-EM projects prior to the establishment of the Midlands Facility. |
Start Year | 2018 |
Description | Midlands Regional Partners using the Cryo-EM Facility-Update |
Organisation | University of Nottingham |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The Midlands Regional Cryo-EM Facility was setup to serve the expanding Cryo-EM needs of the Midlands. The university of Leicester has provided the facilities to accommodate the Titan Krios microscope and employs a facility manager to run this facility. In addition, a high performance computer cluster was setup with a dedicated manager that allows data collected from the microscope to be processed on-site leading to high resolution 3D structures. The regional partners have access in the form of 20 days per year for data collection for a period of 5 years commencing in 2018. In addition all partners can process their data on the high performance cluster. The university of Leicester facility managers are also responsible for training of new users from the Midlands in specimen preparation, data collection and data processing. In addition Leicester offers an annual Midlands Cryo-EM workshop where 4 participants from each partner university can attend and learn the basics of Cryo-EM. In 2021 the workshop was conducted entirely online and included lectures from experts in the field and a hand-on image processing tutorial. In addition to the workshop, online tutorials for data collection have also taken place benefitting not only our Midlands partners but also external users from the UK and Europe that make use of the Midlands facilities. Lecture videos and slides have been made available to the Midlands community via our website (https://le.ac.uk/liscb/facilities-and-technologies/cryo-electron-microscopy/guides-and-learning-resources). Finally a weekly Data Processing Club is held online to discuss data processing, microscopy or developments in the field. |
Collaborator Contribution | Each regional partner has contributed £200,000 to the cost of setting up the facility. In addition the university of Warwick serves as the screening hub for projects to build up before collecting data at Leicester. The regional partners are using the facility on high impact projects that will lead to high-quality publications. |
Impact | To date over 70 high-resolution structures of biological macromolecules have been determined using the Midlands Titan Krios (Including industry user structures which will not be published). To this date there have been 16 publications in total of which 9 are from Midlands universities. Several more have been submitted for review and/or submitted to pre-print servers. A total of 25 groups from the four Midlands Universities are now involved in Cryo-EM projects of which only 6 were involved in Cryo-EM projects prior to the establishment of the Midlands Facility. |
Start Year | 2018 |
Description | Midlands Regional Partners using the Cryo-EM Facility-Update |
Organisation | University of Warwick |
Department | Warwick Evidence |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The Midlands Regional Cryo-EM Facility was setup to serve the expanding Cryo-EM needs of the Midlands. The university of Leicester has provided the facilities to accommodate the Titan Krios microscope and employs a facility manager to run this facility. In addition, a high performance computer cluster was setup with a dedicated manager that allows data collected from the microscope to be processed on-site leading to high resolution 3D structures. The regional partners have access in the form of 20 days per year for data collection for a period of 5 years commencing in 2018. In addition all partners can process their data on the high performance cluster. The university of Leicester facility managers are also responsible for training of new users from the Midlands in specimen preparation, data collection and data processing. In addition Leicester offers an annual Midlands Cryo-EM workshop where 4 participants from each partner university can attend and learn the basics of Cryo-EM. In 2021 the workshop was conducted entirely online and included lectures from experts in the field and a hand-on image processing tutorial. In addition to the workshop, online tutorials for data collection have also taken place benefitting not only our Midlands partners but also external users from the UK and Europe that make use of the Midlands facilities. Lecture videos and slides have been made available to the Midlands community via our website (https://le.ac.uk/liscb/facilities-and-technologies/cryo-electron-microscopy/guides-and-learning-resources). Finally a weekly Data Processing Club is held online to discuss data processing, microscopy or developments in the field. |
Collaborator Contribution | Each regional partner has contributed £200,000 to the cost of setting up the facility. In addition the university of Warwick serves as the screening hub for projects to build up before collecting data at Leicester. The regional partners are using the facility on high impact projects that will lead to high-quality publications. |
Impact | To date over 70 high-resolution structures of biological macromolecules have been determined using the Midlands Titan Krios (Including industry user structures which will not be published). To this date there have been 16 publications in total of which 9 are from Midlands universities. Several more have been submitted for review and/or submitted to pre-print servers. A total of 25 groups from the four Midlands Universities are now involved in Cryo-EM projects of which only 6 were involved in Cryo-EM projects prior to the establishment of the Midlands Facility. |
Start Year | 2018 |
Title | Relion External Tool Integration |
Description | A lot of new software tools are being developed for Cryo-EM. Most users aren't comfortable swapping over-and-over between different packages and as a result recent advances get under-utilised by the community. We developed a software package for integrating external programs into RELION more easily. Now a single individual, with basic Python programming skills, can integrate new features into Relion. Our users routinely use several external programs without the learning curve usually associated with new, diverse software. |
Type Of Technology | Software |
Year Produced | 2020 |
Impact | The users of the Midlands facility have been using this software in their projects to employ new picking algorithms and new refinement tools. We have also shared this tools with other labs who are making use of it. |
Description | Midlands annual Cryo-EM workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Other audiences |
Results and Impact | The annual Cryo-EM workshop hosted at the university of Leicester is set out to train new users from each partner university in getting started with Cryo-EM. Some of the students have returned to initiate Cryo-EM projects that will use the Titan Krios. Some of the students were group leaders who want to be educated more on Cryo-EM. Each workshop accommodates 16 participants. Due to the Covid pandemic the 2020 workshop was moved to March 2021 and is this year taking place in an entirely online format which enables many more participants to observe the lectures and tutorials. The next Cryo-EM workshop is scheduled for autumn 2022. |
Year(s) Of Engagement Activity | 2018,2019,2021 |
URL | https://le.ac.uk/liscb/facilities-and-technologies/cryo-electron-microscopy/guides-and-learning-reso... |
Description | Online Data Collection Tutorial |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The Midlands regional Cryo-EM Facility organised an online tutorial on data collection on a Titan Krios using the EPU software. The audience consisted of ~ 30 Midlands academic users , UK external academics and users from Industry. The scope of the tutorial was to teach the steps involved in data collection on the Krios so that users can begin to collect their data in a more independent manner and to introduce new users to the technique.The participants also followed the tutorial remotely and had access to a PDF with instructions on how to setup data collection. |
Year(s) Of Engagement Activity | 2021 |
Description | Wellcome Cryo-EM Training Single Particle Workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | This was the 1st workshop carried out between the Universities of Leicester and University of Leeds to train students, postdocs and PIs in microscope operation for Cryo-EM Single particle data acquisition under the successful UK community based Cryo-EM training grant funded by the Welcome Trust.. Leicester also provided an image processing demonstration as well as online lectures along with Birkbeck and eBIC. |
Year(s) Of Engagement Activity | 2021 |
URL | https://astbury.leeds.ac.uk/facilities/wellcome-mrc-training-in-cryoem/ |
Description | Wellcome Cryo-EM Training Tomography Workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | This was the 2nd workshop carried out between the Universities of Leicester and University of Leeds to train students, postdocs and PIs in microscope operation for Cryo-EM Tomography data acquisition under the successful UK community based Cryo-EM training grant funded by the Welcome Trust.. |
Year(s) Of Engagement Activity | 2022 |
URL | https://astbury.leeds.ac.uk/facilities/wellcome-mrc-training-in-cryoem/ |
Description | Wellcome Cryo-EM Training Tomography Workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | This was the 1st workshop carried out between the Universities of Leicester and University of Leeds to train students, postdocs and PIs in microscope operation for Cryo-EM Tomography data acquisition under the successful UK community based Cryo-EM training grant funded by the Welcome Trust.. |
Year(s) Of Engagement Activity | 2022 |
URL | https://astbury.leeds.ac.uk/facilities/wellcome-mrc-training-in-cryoem/ |