Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM): Supporting the software infrastructure for cryoEM techniques.

Lead Research Organisation: STFC - Laboratories
Department Name: Scientific Computing Department

Abstract

Understanding how biological molecules function inside cells is vital to combating disease. While experimental techniques such as macromolecular crystallography and nuclear magnetic resonance spectroscopy have for many years given detailed information on important molecules in the cell, attention is now moving to how these molecules interact with each other and how they are affected by their location in the cell. Electron cryo-Microscopy (cryo-EM) provides very useful information here, and bridges the gap between individual molecules and the whole cell. In the most favourable cases, detailed images of assemblies of molecules can be obtained, while at lower resolutions electron tomograms can show internal molecular details from within intact parts of cells or tissues. Advances in instrumentation and data processing have led to a significant increase in the application of cryo-EM in recent years, such that it is now one of the most important experimental techniques available in structural and cellular biology.

To exploit fully cryo-EM requires good software for processing the primary experimental data and for interpretating it in terms of molecular or cellular structure. However, software provision is patchy and fragmented, and individual labs face a steep learning curve when trying to create a suitable software environment for their projects. The macromolecular crystallography community faced such a challenge more than 30 years ago, and the Collaborative Computational Project No. 4 (CCP4) was created to address this challenge. In the years following, CCP4 has grown to be a major international project, and has underpinned many of the advances in our understanding of cells at the molecular level. In the last 10 years, similar collaborative projects for structural biology have been created: CCPN for nuclear magnetic resonance spectroscopy, CCPBioSim for biomolecular simulation, and CCP-SAS for small angle X-ray and neutron scattering. In response to the growing scientific role of cryoEM, we have recently created the Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM).

There are at least 25 groups in the UK active in the field of cryo-EM, with a rapidly increasing number of crystallography groups looking to obtain complementary information from cryoEM. CCP-EM is open to all these groups, and will coordinate efforts within the UK community. It will support users through dissemination of information on available software, helpdesk support, and directed training. It will support developers through technical help and by helping to distribute their software to the community. CCP-EM is also developing its own software suite for processing cryoEM data by integrating existing programmes into a robust and user-friendly framework. The creation of CCP-EM was facilitated by the award of a Partnership Grant, and we now seek a follow-on Partnership Grant to support the collaborative project as it matures and expands. While the first grant focussed on single particle techniques, wherein individual molecules or complexes are imaged, we now proposed to expand the scope to electron tomography which provides in situ imaging of complexes and larger structures in the cell.

A continuation of CCP-EM will lead to a better use of software within UK groups. The support of a dedicated group of scientists will greatly speed up the process of establishing new groups or helping established microscopists move into new areas (such as tomography). CCP-EM will directly support the new national EM facility on the Harwell Campus, helping users get the most from a new resource. However, the most important output is the development of a community spirit, that encourages individual scientists to pool their efforts. The creation of scientific communities in the UK leads to the best use of public money, and maximises the return on the UK's investment in microscopy facilities

Technical Summary

The aims of CCP-EM will be achieved through two computational scientists based at the Research Complex at Harwell, directed by 10 investigators active in cryoEM. The PDRAs will maintain the necessary infrastructure in terms of community events, software development environment, and collaboration tools. Together with the named investigators, they will consult the whole community on software requirements. Specifically, they will continue to develop the CCP-EM software framework, and integrate existing programs via close collaboration with scientists/developers in the wider community. The framework has been developed in Python/PyQt which is suitable for integration of disparate programmes. A database backend allows recording of compute jobs, and subsequent review or modified re-run. The CCP-EM PDRAs will also organise conferences and workshops, in order to train new students or scientists entering from another field. These events will include training in specific software, and also more general workshops on issues of common interest.

The outputs of the project will include an easy-to-install and easy-to-use software suite, additional tools and resources on the web site, a substantial number of training days delivered, and a range of community events and conferences. Usage of these various resources will be promoted by the investigators and the members of Working Group 1, and monitored via downloads and registrations. The PI and the co-investigators will be responsible for linking CCP-EM activities to other structural biology disciplines, and to the international community. In particular, the PI has a background in the CCP4 project for crystallography, one co-I has responsibility for the Electron Microscopy Data Bank at the EMBL-EBI, and one co-I has led the effort to establish a national EM facility.

Planned Impact

In the international research community, there is widespread interest in using cryo-EM to tackle big challenges, such as molecular machines in action and membrane complexes in situ. The field has strong links to atomic structure methods, especially crystallography, while electron tomography has strong connections to cell biology. The spatial dimension is needed to understand biological networks and machines, and complements traditional systems biology approaches. By supporting cryo-EM research groups in the UK and encouraging a collaborative effort, CCP-EM advances the usage of cryoEM, and has an impact on many structural biology projects.

CCP-EM will also have an impact on individual researchers through its training and knowledge exchange aspects. The expansion of cryo-EM as an important component in the toolkit for understanding cellular and sub-cellular biology relies on the availability of researchers competent in the computational techniques required to interpret the data. Existing researchers will of course benefit through improved software tools and environment. However, we specifically wish to lower the barriers to entry into the field of cryo-EM. This applies not only to students and young postdocs, but also to researchers moving from other fields or wishing to use cryo-EM as an additional technique.

The problems being addressed by cryo-EM are of major importance in biomedical science, e.g. dynamic systems involving protein folding/refolding/misfolding, important in neurodegeneration and other misfolding diseases, virus-host interactions, and chromatin structure and modification. Although our primary focus in the Partnership is on the fundamental science, advances here ultimately have an impact on translational and medical research. We are focussing on a technique rather than a particular scientific area, so the impact is likely to be very broad, leading eventually to improved medicine and health for the nation.

The insight that cryoEM provides to disease mechanisms is attracting the attention of a number of pharmaceutical companies. Representatives from at least half-a-dozen companies have either made enquiries or registered for a CCP-EM event. As well as helping to elucidate the underlying mechanisms of disease, cryoEM allows scientists to visualise the effect of drug molecules on proteins and complexes, in a near-native environment. As the technique matures, it is likely to become part of the drug development pipeline. Other industries (biotechnology, agribusiness) will also potentially benefit from the extra insight into biological processes provided by cryo-EM.

By uniting the UK cryo-EM community, the Partnership will have an impact on the strategy for future developments. By acting together, the UK cryo-EM community will have a stronger voice. This will be used to influence software developers, instrument manufacturers and standards development. They will also be able to provide input for national and international policy makers and funders. Finally, CCP-EM will take part in public engagement events to help strengthen the public understanding and appreciation of biomedical research.

Publications

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Beckers M (2020) Confidence maps: statistical inference of cryo-EM maps. in Acta crystallographica. Section D, Structural biology

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Bullock JMA (2018) Modeling Protein Complexes Using Restraints from Crosslinking Mass Spectrometry. in Structure (London, England : 1993)

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Burnley T (2017) Recent developments in the CCP-EM software suite. in Acta crystallographica. Section D, Structural biology

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Burnley T (2018) Proceedings of the third CCP-EM Spring Symposium. in Acta crystallographica. Section D, Structural biology

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Burnley T (2017) Introducing the Proceedings of the CCP-EM Spring Symposium. in Acta crystallographica. Section D, Structural biology

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Cragnolini T (2021) TEMPy2: a Python library with improved 3D electron microscopy density-fitting and validation workflows. in Acta crystallographica. Section D, Structural biology

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Cragnolini T (2021) Cryo-EM targets in CASP14. in Proteins

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Hoh SW (2020) Current approaches for automated model building into cryo-EM maps using Buccaneer with CCP-EM. in Acta crystallographica. Section D, Structural biology

 
Description Frontiers in Cryo-EM Validation Workshop
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a national consultation
Impact The workshop brought together leading international experts in cryoEM for life sciences, to consider metrics and tools for ensuring the quality of data analysis. The outputs of cryoEM analysis are deposited in the EMDB and PDB archives, from where they are accessed by scientists in other disciplines. The quality of the deposited data has a downstream effect on multiple sectors that use structural data, including pharmaceutical, biotechnology, agrochemical, etc. The workshop was funded by a Wellcome Trust grant, but had significant input from several CCP-EM partners (who are investigators on the Wellcome Trust grant). A white paper is in preparation which will set out recommendations for data quality, and the conditions for deposition in EMDB/PDB and for publication in journals where the structure is central to the article.
 
Description Member of STFC advisory panel on Life Sciences and Soft Materials
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Model Metrics Challenge
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a national consultation
Impact The Challenge was organised by the global EM Data Resource https://www.emdataresource.org to assess the state-of-the-art in quality assessment of structural models fitted into cryoEM data. These models are deposited into international databases, and used downstream for many applications (typically in healthcare). Our participation help to set the quality standards which will be applied to future depositions. Results and recommendations have been published in Nature Methods https://doi.org/10.1038/s41592-020-01051-w with a News and Views commentary at https://doi.org/10.1038/s41592-021-01062-1 We are now (2021) participating in another Challenge organised by the EM Data Resource.
URL https://challenges.emdataresource.org/?q=model-metrics-challenge-2019
 
Description Presentation on cryoEM to STFC Leadership Conference
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact Tom Burnley (CCP-EM) was invited to give a talk on the status of cryoEM in the UK, following the award of a Nobel Prize in this area. The conference included senior management of STFC. The expectation is that this input will help to improve the provision of cryoEM hardware and software in the UK, with downstream benefits to health and biotechnology.
 
Description Working groups for Volume EM national infrastructure
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description wwPDB single-particle EM data-management workshop 2020
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a national consultation
Impact The wwPDB convened international experts in cryoEM to determine the minimum data requirements for depositing biological structures in the international PDB/EMDB repositories. The aim is to ensure high quality of deposited data, and to allow validation and re-use of that data. Several members of CCP-EM contributed actively to the discussion, which is to be written up in a White Paper.
 
Description Automated de novo building of protein models into electron microscopy maps
Amount £342,000 (GBP)
Funding ID BB/P000975/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 02/2017 
End 02/2020
 
Description Benchmarking for AI for Science at Exascale (BASE)
Amount £284,104 (GBP)
Funding ID EP/V001310/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 05/2020 
End 08/2021
 
Description CCP-EM: development of an integrated software pipeline for cryo-EM
Amount £128,222 (GBP)
Funding ID PoCF1920-06 
Organisation Science and Technologies Facilities Council (STFC) 
Sector Public
Country United Kingdom
Start 05/2020 
End 12/2022
 
Description Intermediate-to-low resolution feature detection in cryoEM maps using cascaded neural networks
Amount £147,999 (GBP)
Funding ID BB/T012064/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 03/2020 
End 03/2021
 
Description Technology Development Grant 2017
Amount £1,187,077 (GBP)
Funding ID 208398/Z/17/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2018 
End 03/2021
 
Description Timestamping Integrative Approach to Understand Secondary Envelopment of Human Cytomegalovirus
Amount £673,700 (GBP)
Funding ID 209250/Z/17/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2018 
End 03/2023
 
Title Establishment of Scottish Centre for Macromolecular Imaging 
Description I led a successful consortium bid to secure funding for a Scottish national centre for CryoEM. Based in the University of Glasgow, this centre will provide access to world-class structural biology resources for Scotland and Northern England. 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? Yes  
Impact The centre is still in the installation phase. 
 
Title Flex-EM for high resolution EM 
Description We improved the Flex-EM method to make it applicable for refinement of high-resolution 3D electron microscopy maps 
Type Of Material Improvements to research infrastructure 
Year Produced 2016 
Provided To Others? Yes  
Impact We have used the method to refine a number of new structure, in particular GroEL and microtubule-bound complexes. 
URL http://topf-group.ismb.lon.ac.uk/flex-em/
 
Description AIMLAC CDT - Aberystwyth, Bangor, Cardiff, Swansea, Bristol 
Organisation Swansea University
Country United Kingdom 
Sector Academic/University 
PI Contribution We provide placements for students on this CDT programme. Specifically for the 2020/2021 cohort, we provided 2 placements. The students worked on projects concerning denoising of electron micrographs for cryoEM, and modelling of neutron reflectometry data. Each student has completed a 2 week initial placement, followed by the main 6 month placement. For the 2021/2022 cohort, we are providing a further 2 placements. One will continue to refine the cascade machine learning model for segmentation of molecular volumes from cryoEM. The other will work on the CoVal server for linking SARS-CoV-2 variant data with experimental structures.
Collaborator Contribution The CDT administers the programme, and matches us up with specific students. The students themselves contribute to our on-going research programme. Typically, they deliver a small piece of coding which can be included in our larger software packages.
Impact No outputs yet. The collaboration is multi-disciplinary in the sense that the students come from a background of AI in physical sciences, and contribute to projects in the biosciences when with us.
Start Year 2020
 
Description COG UK 
Organisation University of Cambridge
Department School of Clinical Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution We have developed the CoVal web service for matching sequence mutations of SARS-Cov-2 to available structural data. We have made this server available to members of the COVID-19 Genomics UK Consortium (COG-UK). We are attending weekly meetings with COG-UK and discussing how we can input structural data into the understanding of the emergence of SARS-Cov-2 variants.
Collaborator Contribution The members of COG UK are providing advice on variants of interest, which we can focus on for the CoVal server. We expect to get early access to sequence data in the UK.
Impact The collaboration brings together our structural biology expertise with the sequencing/bioinformatics expertise of COG-UK. It is still early days, but we hope to feed into the scientific/policy advice which COG UK gives to the UK government.
Start Year 2020
 
Description Collaboration with CCP-EM 
Organisation Daresbury Laboratory
Country United Kingdom 
Sector Private 
PI Contribution We collaborate on the CCP-EM (Collaborative Computational Project for Electron cryo-Microscopy) project. This project is supported by MRC. We implement some of the software developed in my group via the CCP-EM platform. The idea is to support the users of software for cryo-EM through dissemination of information on available software, and directed training.
Collaborator Contribution Our collaborators (under the supervision of Dr. Martyn Winn) are in the process of making our Flex-EM/RIBFIND software as well as TEMPy available via CCP-EM.
Impact We had a number of productive meetings and workshops. We are working on a number of software packages developed in my group to be implemented in CCP-EM (Flex-EM, RIBFIND, TEMPy). publications: Wood et al. (2015) PMID: 25615866 Joseph et al (2016) PMID: 26988127 Joseph et al (2017) PMID: 28552721 We received a joint MRC Partnership grant together with Martyn Winn (PI) and other 9 Co-Is across the UK. (MR/N009614/1)
Start Year 2012
 
Description Coronavirus Structural Task Force 
Organisation University of Hamburg
Country Germany 
Sector Academic/University 
PI Contribution The Coronavirus Structural Task Force aims to provide structural information on proteins from the SARS-Cov-2 virus. As well as structures from the internatinoal repositories PDB and EMDB, the Task Force provides quality assessment, and in some cases improved structural modelling. Joseph Agnel from the CCP-EM team has provided many of the validation tools used by the Task Force, and has improved some of the viral structures and deposited them on their web site.
Collaborator Contribution Our partners provide the dissemination site for our efforts to improve the structural modelling for SARS-Cov-2.
Impact The collaboration is between structural biologists from different international groups.
Start Year 2020
 
Description DATA INTENSIVE CDT - Cardiff, Bristol and Swansea 
Organisation Cardiff University
Department School of Physics and Astronomy
Country United Kingdom 
Sector Academic/University 
PI Contribution We are hosting a PhD student from the DATA INTENSIVE CDT (Cardiff, Bristol and Swansea), suggesting a placement project to work on, and providing the office space and environment at STFC Rutherford Appleton Laboratory. The student visited for 2 weeks in February 2019, and returned for 6 months in late 2019. His main PhD project is on neutrino detection, but he is working for us on a problem in cryoEM. The linking theme is the use of machine learning. We are also hosting a second PhD student from the following year's cohort, again in the area of machine learning for cryoEM. He completed his 2 week placement in February 2020. His 6 month placement was delayed due to Covid19 but has just started (early 2021).
Collaborator Contribution Organisation of the programme and supply of suitable students from the universities of the CDT. The student will contribute to our on-going research efforts on the application of machine learning to problems in cryoEM.
Impact The first student has helped develop code for classifying protein residues in high resolution cryoEM maps, and has performed several rounds of training with this code. He presented this work at an internal seminar in February 2020. Work to turn this into a tool for structural biologists is on-going (and will continue after the end of the placement).
Start Year 2019
 
Description Global Phasing Ltd collaboration 
Organisation Global Phasing
Country United Kingdom 
Sector Private 
PI Contribution We bring prior work on development of a software framework for single particle analysis by Relion, which the partnership is building on. We also bring our established relationship with the Relion development team, with the eBIC facility, and with the wider community.
Collaborator Contribution Global Phasing Ltd bring expertise on developing automated data processing pipelines in crystallography, as well as specific software such as Buster. Their contribution is in terms of background IP and current staff effort.
Impact The output will be improved software for processing single particle cryoEM datasets, which will be deployed at the eBIC facility and distributed as part of the CCP-EM software suite. The project is supported by internal funds of Global Phasing and CCP-EM, as well as a Proof of Concept award from STFC. Prototype software has been developed, and a first version will be released soon. The work combines structural biology, data management and software engineering.
Start Year 2019
 
Description Learning a prior for cryo-EM structure determination 
Organisation Royal Institute of Technology
Country Sweden 
Sector Academic/University 
PI Contribution We collaborate with Carola Schoenlieb at the dept of Applied Mathematics of the University of Cambridge and with Ozan Oktem at the KTH in Stockholm to develop the mathematics required for incorporating informative priors in cryo-EM structure determination through deep learning approaches. We implement such developments into our software package RELION.
Collaborator Contribution Carola and Ozan help with mathematical derivations and proofs.
Impact A first paper on this work has now been published (Kikmanius et al, IUCrJ 2021).
Start Year 2019
 
Description Learning a prior for cryo-EM structure determination 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution We collaborate with Carola Schoenlieb at the dept of Applied Mathematics of the University of Cambridge and with Ozan Oktem at the KTH in Stockholm to develop the mathematics required for incorporating informative priors in cryo-EM structure determination through deep learning approaches. We implement such developments into our software package RELION.
Collaborator Contribution Carola and Ozan help with mathematical derivations and proofs.
Impact A first paper on this work has now been published (Kikmanius et al, IUCrJ 2021).
Start Year 2019
 
Description Leeds EM facility 
Organisation University of Leeds
Department Astbury Biostructure Laboratory
Country United Kingdom 
Sector Academic/University 
PI Contribution Help to scope computational requirements of the new Electron Microscopy facility. Later, we will help with installation, and writing of custom software pipelines. We have contributed to training events held at Leeds in Sept 2016, July 2017 and Dec 2018.
Collaborator Contribution Advice on software required by Electron Microscopy facilities. This advice was included in a grant application submitted in February 2016, as well as informing on-going plans. Neil Ranson was included as a CoI in the 2020 proposal for the renewal of CCP-EM.
Impact Material for inclusion in the CCP-EM renewal grant application, concerning the software infrastructure needs of cryoEM facilities. Election of Neil Ranson (Leeds) as Deputy Chair of CCP-EM. Leeds hosted a Relion workshop in September 2016, an MD/EM workshop in July 2017 and a cryoEM workshop in Dec 2018.
Start Year 2015
 
Description Modelling microtubule with microtubule binding proteins 
Organisation Birkbeck, University of London
Department Department of Biological Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution We have been generating atomic models of microtubule complexes using 3D cryoEM density maps.
Collaborator Contribution Professor Carolyn Moores studies microtubule organisation and dynamics using cryo electron microscopy methods.
Impact Atherton et al 2014 (PMID: 25209998) Atherton et al 2017 (PMID: 28826477) Atherton et al 2017 (PMID: 28991265) Locke et al 2018 (PMID: 29078367)
Start Year 2014
 
Description eBIC collaboration 
Organisation Diamond Light Source
Country United Kingdom 
Sector Private 
PI Contribution eBIC (electron Bio-Imaging Centre) at Diamond Light Source provides scientists with state-of-the-art experimental equipment and expertise in the field of cryo-electron microscopy, for single particle analysis and cryo-tomography. As part of CCP-EM, my group are providing computational support to users of eBIC, in the form of installing software and direct assistance. We benchmark certain key codes, and have optimised their usage on Diamond compute clusters. We plan to co-develop software pipelines to enable users to get rapid feedback on their data collection.
Collaborator Contribution eBIC provides a pool of cryoEM users who can provide feedback on the developing CCP-EM software suite, and provide test datasets. Diamond staff will also help to co-develop software pipelines for rapid feedback.
Impact The collaboration involves hardware development (microscope and computational resources), application software development, and structural biology. We maintain a set of EM software on Diamond systems, available to users of eBIC. We have benchmarked version 2.0 of the Relion software on a GPU platform at Diamond. We have helped with the installation of cryoSPARC at Diamond. We have implemented the Relion-IT pipeline for automatic processing of micrographs during a user visit, and are now trialling the CCP-EM pipeliner.
Start Year 2015
 
Title CCP-EM software suite 
Description The software developed by the CCP-EM consortium under several awards is licensed for use by structural biologists. The software allows the solution of macromolecular structures by electron cryo-microscopy. 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2018
Licensed Yes
Impact CCP-EM software is licensed for commercial and non-commercial use by structural biologists around the world. The licence allows for the installation and use of the CCP-EM software suite for solving macromolecular structures by electron cryo-microscopy. It does not permit re-distribution, except insofar as individual components may have more permissive terms. The CCP-EM software suite is being used by numerous research groups for generating maps and atomic models, which are then deposited in the international databases EMDB and PDB, and so has a lasting impact on structural biology. See http://www.ccpem.ac.uk/download.php for more details.
 
Title A Python implementation of the MRC2014 file format 
Description mrcfile.py is a Python implementation of the MRC2014 file format, which is used in structural biology to store image and volume data. It allows MRC files to be created and opened easily using a very simple API, which exposes the file's header and data as numpy arrays. The code runs in Python 2 and 3 and is fully unit-tested. The intent of this library is to allow users and developers to read and write standard-compliant MRC files in Python as easily as possible, and with no dependencies on any compiled libraries except numpy. You can use it interactively to inspect files, correct headers and so on, or in scripts and larger software packages to provide basic MRC file I/O functions. 
Type Of Technology Software 
Year Produced 2016 
Open Source License? Yes  
Impact None yet. 
URL https://github.com/ccpem/mrcfile
 
Title Buccaneer in CCP-EM 
Description The Buccaneer pipeline is available within the CCP-EM graphical user interface. Given a cryoEM map, obtained for example from single particle reconstruction, and the sequence of the expected protein molecules, the pipeline will build and refine an atomic model. This is a crucial step in the interpretation of experimental data from cryoEM. In comparison to other model building tools, Buccaneer can handle relatively low resolution. Buccaneer is an important part of the annual CCP-EM Icknield training school on model building and refinement. It was also used in our team's submission to the 2019 Model Metrics Challenge (organised by the global EM Data Resource https://www.emdataresource.org/). 
Type Of Technology Software 
Year Produced 2017 
Impact The pipeline has been used in CCP-EM workshops, and has helped several researchers with their structural biology projects. The Buccaneer pipeline remains an important component of the CCP-EM software suite, and is updated periodically by the main author. 
 
Title CCP-EM software beta release 
Description CCP-EM intends to distribute a software suite containing tools for cryo-EM. At present, a beta-release is available for Linux64. This is available as part of the CCPEM / CCP4 nightly build, with which it shares a build system and some libraries and programs. In due course, a slimmer version will be available. 
Type Of Technology Software 
Year Produced 2016 
Impact Used to support the CCP-EM contribution to the Instruct course: From 2D images to 3D structures, Madrid, May 17 - 20, 2016. 
URL http://www.ccpem.ac.uk/download.php
 
Title CCP-EM version 1 
Description The CCP-EM software suite provides a collection of programs for cryoEM single particle reconstruction and building of atomic models. The suite as a whole has an STFC licence, and is licensed free of charge to non-profit users, and for a charge to for-profit users. Nevertheless, many of the component programs are available separately under Open Source licences. Version 1 was released April 2018, with updates 1.1 in July 2018, 1.2 in December 2018, 1.3 in April 2019, 1.4 in November 2019 and 1.5 in October 2020. This first official release of the CCP-EM software suite mainly covered fitting and refinement of atomic models into single particle reconstructions, combining experience gained in CCP4 with high resolution maps with other techniques more appropriate to lower resolution maps. Since that initial release, the suite has expanded to include tools for map analysis and manipulation. Version 1.2 included for the first time pre-compiled binaries for Relion, the most popular software for single particle reconstruction. Besides providing a convenient way of viewing Relion projects on a personal machine, the inclusion of Relion is the basis of on-going efforts to integrate reconstruction with downstream map interpretation. The CCP-EM suite also includes software libraries such as mrcfile, clipper-python and relion-it, which are being used by third-party developers and facility sites for customised workflows. Version 1.6 is in preparation. Meanwhile, stable nightly builds are made available (latest 25/01/22) which contain some useful updates. 
Type Of Technology Software 
Year Produced 2018 
Impact The suite is used by many academic and industrial cryoEM groups worldwide to solve novel macromolecular structures. These are deposited in the Electron Microscopy Data Bank (EMDB) and the Protein Data Bank (PDB), from where they can be employed in wider biomedical applications. We estimated that v1.3 was downloaded around 1500 times, with later versions downloaded at least that much (it is difficult to estimate unique downloads, and has not been done recently). The two papers describing the suite itself have been cited 216 times to date (as at March 2022), with individual programs from the suite cited many more times. 
URL http://www.ccpem.ac.uk/download.php
 
Title CoVal 
Description CoVal is a repository of amino acid replacement mutations identified in the SARS-CoV-2 genome sequences, mapped onto the cryo-EM derived protein structures. We provide information on the demographic distribution of these mutations, and report co-occuring mutations. Upon mapping these mutations, we inspect the mutation site for its structural interactions and neighbors. We further provide various validation scores for global quality of the structures, and the local quality of mutation site(s) and the structural neighbors. 
Type Of Technology Webtool/Application 
Year Produced 2020 
Impact The site has been accessed several thousand times. It is of interest to the Covid19 Genomics UK consortium (COG-UK), and was reported in their Blog https://www.cogconsortium.uk/visualisation-tools-to-help-understand-sars-cov-2-mutations/ 
URL https://coval.ccpem.ac.uk/
 
Title LAFTER 
Description LAFTER is an algorithm for de-noising single particle reconstructions from cryo-EM. Single particle analysis entails the reconstruction of high-resolution volumes from tens of thousands of particle images with low individual signal-to-noise. Imperfections in this process result in substantial variations in the local signal-to-noise ratio within the resulting reconstruction, complicating the interpretation of molecular structure. An effective local de-noising filter could therefore improve interpretability and maximise the amount of useful information obtained from cryo-EM maps. LAFTER is a local de-noising algorithm based on a pair of serial real-space filters. It compares independent half-set reconstructions to identify and retain shared features that have power greater than the noise. It is capable of recovering features across a wide range of signal-to-noise ratios. A fast and computationally efficient implementation of LAFTER is freely available, and is part of the CCP-EM software suite. LAFTER was jointly developed by Chris Aylett's group at Imperial College and Colin Palmer in the CCP-EM core team. 
Type Of Technology Software 
Year Produced 2018 
Open Source License? Yes  
Impact It is used as part of the CCP-EM software suite, and in teaching schools. 
URL https://www.ncbi.nlm.nih.gov/pubmed/30502495
 
Title RELION 
Description Objective structure determination with cryo-EM data. 
Type Of Technology Software 
Year Produced 2011 
Open Source License? Yes  
Impact RELION is currently the most widely used cryo-EM structure determination software package in the world. It has been used for 30% of all structures in the EMDB and RELION-related papers attract more than 2000 citations every year. 
URL http://www2.mrc-lmb.cam.ac.uk/relion
 
Title RelionIt 
Description In general, Relionit provides the ability to run a cryoEM single particle workflow, with job scheduling being handled automatically. In principle, the pipelining will go as far as 3D classification and subsequent template-based particle picking. The software has been developed as part of the broader Relion package, and CCP-EM core staff have contributed to a lightweight GUI and the documentation. The development has been largely driven by the data processing needs of the eBIC cryoEM facility. CCP-EM core staff have installed RelionIt at eBIC and provided appropriate templates (which specifies options, including access to the Diamond GPU cluster). 
Type Of Technology Software 
Year Produced 2018 
Open Source License? Yes  
Impact RelionIT is installed at the eBIC microscopes, and is beginning to be used by scientists there. 
 
Title SIDESPLITTER 
Description Over-fitting remains an issue within regions of low local signal-to-noise in reconstructed cryoEM volumes refined using the half-set strategy. We propose a modified filtering process during refinement through the application of a local signal-to-noise filter, SIDESPLITTER, which we show to be capable of reducing over-fitting in both idealised and experimental settings, while maintaining independence between the two sides of a split refinement. SIDESPLITTER can also improve the final resolution in refinements of structures prone to severe over-fitting, such as membrane proteins in detergent micelles. 
Type Of Technology Software 
Year Produced 2020 
Open Source License? Yes  
Impact The method has been published in J Struct Biol https://doi.org/10.1016/j.jsb.2020.107545 The software is beginning to be used by structural biologists, with encouraging feedback. 
 
Description 2nd CCP4/BGU Workshop on Advanced Methods for Macromolecular Structure Determination, Ben-Gurion University 
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 CCP4/BGU workshop is directed to 25 graduate students, postdocs and/or researchers with some previous expertise in crystallography and/or Cryo-EM who need a deeper insight into most advanced structural biology techniques to carry out their research projects.

The workshop program covers all aspects of structure determination, such as data collection, phasing, model building, refinement, validation and structural analysis.

Tom Burnley and Colin Palmer from the CCP-EM core team presented lectures and tutorials on single particle reconstruction with Relion and model building into cryoEM maps.
Year(s) Of Engagement Activity 2020
URL https://lifeserv.bgu.ac.il/wp/ccp4workshop/
 
Description Article in Microbiology Today - the magazine of the microbiology society 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact David Bhella wrote an article on cryogenic electron microscopy, detailing the recent breakthroughs in the technology and looking to the future.
Year(s) Of Engagement Activity 2016
URL http://www.microbiologysociety.org/publications/microbiology-today/past-issues.cfm/publication/futur...
 
Description Best Practices 2020 
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 We are excited to announce the next meeting in the 'Best practices in CryoEM' series, the first in the series to be hosted online on 12 - 13 October 2020.

Now in its fourth year, the workshop is intended to allow those involved in the running of high-end cryoEM facilities to discuss and share best practice, and is open to EM facility scientists, manager and computing specialists both from academia and industry.

Sessions will include presentations on best practice in sample preparation, imaging and data handling/processing, operational models in light of COVID-19, as well as round table discussions focused on specific topics.

The workshop included a talk from Tom Burnley from the CCP-EM core team, and a breakout session on software pipelines involving Colin Palmer and Matt Iadanza from the CCP-EM team. The workshop is an opportunity for us to promote our software at large cryoEM facilities. Installation of our software at these centres means that it is available to the large number of visiting users. At the workshop, we work with facility managers to make sure the best is got from our software.
Year(s) Of Engagement Activity 2020
URL https://instruct-eric.eu/events/instruct-eric-best-practices-in-cryo-em-workshop/
 
Description Biochemical Society training day 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Biochemical Society Training Day, organised with eBIC and CCP-EM and held at Diamond Light Source on 6 September 2016. The course was aimed at users and potential users of eBIC (electron Bio-Imaging Centre) at Diamond Light Source, UK, and gave attendees:

Awareness of the setup at eBIC, what it can provide and what is expected of users
A good appreciation of the issues surrounding sample preparation for high resolution
A working knowledge of high high resolution EM data collection is achieved
Awareness of how to maximize the quality and amount of data collected during national facility awarded sessions
Appreciation of the requirements and challenges of processing and storage of data gathered during sessions.

I gave a talk on data processing in general, and using CCP-EM as an example of how to do this.
Year(s) Of Engagement Activity 2016
URL https://www.biochemistry.org/Events/tabid/379/View/Conference/MeetingNo/td011/MeetingID/2671/Default...
 
Description CCP-EM Developers Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact We put together a software developer workshop for all involved / interested in CCP-EM. It took place 3-5 Oct 2016, Cosner's House Abingdon (OX14 3JD).

The aim was for a streamlined, informal gathering with emphasis on coding rather than talking. Talks / discussions took place around several software libraries relevant to CCP-EM. There were also discussions on file formats, data compression and validation.

The main outcome was better communication between developers, leading to reduced duplication of code in CCP-EM.

A second CCP-EM Developers Meeting was held on 2-3 Oct 2017, again at the Cosner's House Abingdon. The meeting was attended by 32 software developers, from both the electron microscopy and X-ray crystallography communities. The latter are adapting their tools for the emerging area of cryoEM, and the meeting provides them with an opportunity to present their tools to the EM community, and to learn about particular requirements of cryoEM. Other topics in the meeting included presentations on SuRVoS for tomography segmentation, and FFEA for finite-element based simulations of EM volumes. There were also discussions on validation, and map sharpening. The meeting included representatives from the national eBIC facility, and the Electron Microscopy Data Bank at EMBL-EBI.

We aim to make this an annual meeting.
Year(s) Of Engagement Activity 2016,2017
 
Description CCP-EM Developers Meeting 2016 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact CCP-EM Developers Meeting
Year(s) Of Engagement Activity 2016
 
Description CCP-EM Icknield Model Building Workship 5-7th April 2017 
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 As part of the CCP-EM project we teach graduate students and postdoc how to use our software to model structure in cryo electron microscopy maps
Year(s) Of Engagement Activity 2017
URL http://www.ccpem.ac.uk/training/icknield_2017/icknield_2017.php
 
Description CCP-EM Spring Symposia 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Annual community meeting for biological electron cryo-microscopy organised by the CCP-EM core team. It has a focus on methods development, both experimental and in software, as well as including illustrative applications talks. Attendance has increased each year, and we can now attract high profile international speakers. Details of individual events:
2015: First Spring Symposium held at the STFC Rutherford Appleton Laboratory. 100 attendees. First meeting of the consortium management group "Working Group 1".
2016: Second Spring Symposium held at the STFC Rutherford Appleton Laboratory and Diamond Light Source. 150 attendees.
2017: Third Spring Symposium held in conjunction with the official opening of the eBIC facility at Diamond. 190 attendees.
2018: Fourth Spring Symposium at the University of Keele. 185 attendees. For the first time, the meeting was held off-site.
2019: Fifth Spring Symposium at the Nottingham Jubilee campus. 290 attendees. First day dedicated to an eBIC user meeting. For the first time, we have two members of the academic community as Scientific Organisers - John Briggs / Rebecca Thompson.
2020: Sixth Spring Symposium at the East Midlands Conference Centre, Nottingham. Scientific Organisers - Helen Saibil / Christos Savva
The format which is now established is to have Day 0 dedicated to user meeting for the national cryoEM facility at eBIC, and two days for the main meeting. Talks from the Spring Symposia are published as a special issue of Acta Crystallographica section D. The talks are also live-streamed and available afterwards as videos, to increase the impact of the event.

Some feedback on CCP-EM activities, guiding current direction.
Year(s) Of Engagement Activity 2015,2016,2017,2018,2019
URL http://www.ccpem.ac.uk/symposium.php
 
Description CCP-EM Spring Symposia (virtual) 
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 2020 and 2021 CCP-EM Spring Symposia were held online in a virtual format due to the COVID-19 situation. The conference was hosted on Zoom and was free of charge, but with registration required.

The conference aims to provide a forum to highlight state of the art developments in computational cryoEM and related themes as well as showcasing outstanding recent applications. We aim to promote an inclusive, friendly atmosphere welcoming both old and new to the community. Also included is the Diamond Light Source Biological Cryo-imaging User Meeting (eBIC & B24). Topics include instrument technology, sample preparation, image processing, single particle reconstruction, tomography and model building.

The Scientific organisers for 2020 were Helen Saibil (Birkbeck) and Christos Savva (University of Leicester), and for 2021 Giulia Zanetti (Birkbeck) and Christopher Aylett (Imperial). All other organisation was by STFC.

Because of the online format, we reached a much larger audience than normal. In 2020, we had about 3000 registered, with around 1000 logged in to the sessions at any one time. The numbers were slightly less in 2021, but still much larger than the original in-person meetings. We believe that by the second year of the pandemic, there was some fatigue with the number of on-line conferences. Based on these experiences, we plan to make future Spring Symposia hybrid events, combining the advantages of in-person meetings with the reach and accessibility of on-line meetings.

Speakers slides are made available on our website, and recordings of talks are on YouTube (on the STFC channel, also linked from our website). These are recognised as important resources for our community.
Year(s) Of Engagement Activity 2020,2021
URL https://www.ccpem.ac.uk/symposium.php
 
Description CCP-EM Twitter account 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Twitter account to provide updates on CCP-EM itself, and also general news of interest to our community.To March 2018, we have made 185 tweets, and have 789 followers. To February 2019, we have made 208 tweets and have 1378 followers. To March 2020, we have made 262 tweets, and have 1935 followers.
Year(s) Of Engagement Activity 2015,2016,2017,2018,2019,2020
URL https://twitter.com/ccp_em
 
Description CCP-EM session in CCPN conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact CCP-EM contributed to a special 1 Day Symposium that formed part of the CCPN Conference 2018 on 6-8th September, University of Kent. The morning session covered NMR and Cryo EM Integrated Structural Biology, while Tom Burnley from CCP-EM organised and chaired the afternoon session on EM biological science.
CCP-EM and CCPN are two MRC-supported Collaborative Computational Projects which address computational aspects of two of the major structural biology techniques. This event is part of on-going efforts to link the two communities, and encourage multi-disciplinary projects.
Year(s) Of Engagement Activity 2018
URL https://www.ccpn.ac.uk/meetings/upcoming-meetings/2018-ccpn-conference-canterbury/ccpn-conference-20...
 
Description CCP-EM website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The CCP-EM website is used for dissemination of the aims of CCP-EM, advertising our meetings and workshops, as well as 3rd party meetings of interest to our community.

The CCP-EM software suite is available via the website as downloadable packages. There is a dedicated tutorials page https://www.ccpem.ac.uk/tutorials.php for users to learn how to use the software.

The website also hosts specialist information, such as a description of the MRC file format.
Year(s) Of Engagement Activity 2012,2013,2014,2015,2016,2017,2018,2019,2020,2021,2022
URL http://www.ccpem.ac.uk
 
Description CCP-EM/CCP4 machine learning workshop 
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 CCP-EM co-organised a workshop with CCP4 to bring together multiple efforts around machine learning in structural biology. Attendees from the Harwell Campus, Cambridge, Bristol and Germany agreed to be part of an on-going network, and a further workshop will be held in Spring 2020.
One output was an agreement to host a series of hackathons involving as many of the leading software developers as possible. These hackathons will explore how novel algorithms may be applied to cryoEM, write reference implementations, and publish the outcomes. Obvious examples include new machine-learning approaches, but there may be other areas worth considering in the next 5 years, such as stream processing or quantum computing. This initiative is a direct response to concern in the community about progress in cryo-EM being held back by inappropriate patenting of new numerical methods. CCP-EM cannot solve this on its own, but rather will act as a focal point for community efforts to make new algorithms open and reusable.
Year(s) Of Engagement Activity 2019
 
Description CCP4 Study Weekends 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation workshop facilitator
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The CCP4 Study Weekend is recognised as the best conference for computational methods in macromolecular crystallography (as opposed to those focussed on the scientific results). As such it attracts the leading international developers and an audience of over 400. Each year it provides a snapshot of the state-of-the-art.
Lunchtime bytes provides an opportunity for software developers to demonstrate their programs to the delegates at the meeting. Software from both CCP4 and CCP-EM is demonstrated each year.

The proceedings of each year's conference are published in a special issue of Acta Crystallographica D. Articles in these issues are usually highly cited, as they describe methods used by many crystallographers.
Year(s) Of Engagement Activity Pre-2006,2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016,2017,2018,2019,2020
URL http://www.ccp4.ac.uk/ccp4course.php
 
Description CCPEM contribution to EMBO courses on Image Processing for cryo EM 
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 EMBO course on Image processing for cryo-electron microscopy is held every other year at Birkbeck, and is very popular. Over 10 days, it teaches all aspects of cryoEM including sample preparation, microscope operation, data processing and structure modelling.
The core team of CCP-EM contributed to the 2017 course in several ways. We gave an invited lecture on CCP-EM, and we supported several hands-on computer tutorials. We also directly sponsored the event, allowing more students to be supported.
We contributed again to the 2019 course. This time we ran two practicals: "Fitting of structures, flexible fitting (Flex-EM), model validation (TEMPy)" and "Local sharpening (LocScale), de novo structure building (CCP-EM, REFMAC)". CoIs from the current CCP-EM grant delivered 7 of the lectures. CCP-EM again sponsored the event.
In 2021, CCP-EM collaborators gave several talks, and CCP-EM core staff ran several computer practicals. We again provided sponsorship to help support students. The event was virtual this year, and STFC provided AV support (mainly via Zoom) which we arranged.
The course trains around 50 students and postdocs in cryoEM each time, and is a major contributor to skills development for cryoEM. It is run by Birkbeck College, London, who are an important partner in CCP-EM. In terms of teaching, it is a community effort. In addition to the specific activities mentioned above, CCP-EM plays an indirect role in supporting this community and coordinating efforts.
Year(s) Of Engagement Activity 2017,2019,2021
URL https://meetings.embo.org/event/21-cryo-em
 
Description Cryo-EM Validation in the Age of SARS-CoV-2: Methods, Tools, Applications 
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 This meeting was organised by the UK EM Validation Network to present current thinking on cryo-EM map and map/model validation, and to consider future research directions that anticipate the growing needs in this area. The community effort to apply cryo-EM to structural proteins of SARS-CoV-2 has been a success story but has also highlighted the importance of structure validation. As key members of the Validation Network, CCP-EM were closely involved, and STFC provided the logistical support for the online event.
94 attendees responded to a survey, with overwhelmingly positive feedback.
Year(s) Of Engagement Activity 2020
URL https://www.ccpem.ac.uk/training/validation_symposium_2020/Cryo-EM_Validation_in_the_Age_of_SARS-CoV...
 
Description EMBO course on Practical integrative structural biology, Hamburg 
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 Application of integrative structural biology requires an in-depth understanding of both different experimental approaches and computational modeling. To provide advanced training in such a highly interdisciplinary skill set, this EMBO Practical Course will teach how to interpret data from major structural biology techniques and how to integrate this data using computational methods. The course location at the Hamburg Unit of the European Molecular Biology Laboratory and the Center for Structural Systems Biology on the DESY campus will provide on-site synchrotron SAXS and MX beamlines for training. Hands-on practicals will use a well-studied model system, for which data from all main structural biology techniques are available.
This course was held in November 2019. It included 3 members of the CCP-EM core team and a further 4 members of the cryoEM consortium. We provided lectures and hands-on computer tutorials for cryoEM.
Year(s) Of Engagement Activity 2019
URL https://meetings.embo.org/event/19-integrative-structural-biology
 
Description EMBO course on integrative modelling of biomolecular interactions 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact EMBO course on integrative modelling of biomolecular interactions
Year(s) Of Engagement Activity 2016
URL http://events.embo.org/16-biomol-interact/
 
Description EMBO practical course on cryoEM and image processing 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact EMBO practical course on cryoEM and image processing
Year(s) Of Engagement Activity 2016
URL https://www.embl.de/training/events/2016/CRY16-01/
 
Description Invited talk in the CCP-EM symposium 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact I gave a talk in the CCP-EM symposium 2017. The conference aims to provide a forum to highlight state of the art developments in computational cryoEM and related themes as well as showcasing outstanding recent applications.
Year(s) Of Engagement Activity 2017
URL http://www.ccpem.ac.uk/training/spring_symposium_2017/spring_symposium.php
 
Description Madrid course 
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 course was held at the CNB-CSIC Madrid, May 17 - 20, 2016, sponsored by the Instruct research infrastructure. Tutors addressed the complete image processing workflow typical for macromolecular structural determination, from processing the raw images taken on the electron microscope to the interpretation of the derived 3D volumetric structure in terms of atomistic models. The new CCP-EM suite was introduced to students from across Europe.
Year(s) Of Engagement Activity 2016
URL http://i2pc.cnb.csic.es/hands-on-course-may-2016.html
 
Description Madrid school on model building for cryoEM 
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 Model building and refinement using cryo-EM maps: CCP-EM, Refmac, proSHADE, LocScale, Coot, Scipion.
The course was kindly hosted by Rafael Fernández-Leiro and the Spanish National Cancer Research Center - CNIO over two days in March 2019
This course was aimed at students and postdocs currently in the process of building and refining of atomic models into cryo-EM maps. The course covered the theory and principles behind the software and procedures through a series of seminars and thorough tutorial sessions on the tools widely used by the community. During the workshop there was time to interact with all the speakers and instructors, participants brought their own data to solve specific issues
Year(s) Of Engagement Activity 2019
URL https://www.ccpem.ac.uk/training/madrid_2019/madrid_2019.php
 
Description Relion training course 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation workshop facilitator
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The first one-day training course on Relion was held at Diamond Light Source on Thursday 16th October 2014. It focussed on both theoretical and practical aspects of the RELION software package and was led by the principle developer Dr Sjors Scheres (MRC-LMB), with help from Felix Weis (MRC-LMB) and the local CCP-EM team. A second one-day course was run on 8th December 2014.
The course was held for a 3rd time in Leeds on 19th September 2016. This course was used to introduce the improved GPU-enabled version 2 of Relion. There was also a tour of the new cryoEM facility at Leeds. The 4th edition of this course was held at Bristol in May 2018, in association with the GW4 Alliance.
Two one-day workshops introducing the basics of RELION 3 led by developer and structural biologist Rafael Fernandez-Leiro (Spanish National Centre, Madrid) and assisted by Joshua Lobo (eBIC/Diamond) and the CCP-EM team were held on 18th and 19th February 2019, at Diamond Light Source, UK.
These courses have always been heavily over-subscribed, reflecting the rapid expansion of the field of cryoEM. These courses have also been attended by staff from pharmaceutical and biotechnology companies, who are now looking to include cryoEM in drug discovery pipelines.

This has helped the UK cryoEM community understand the Relion software, so that it can be applied in their research.
Year(s) Of Engagement Activity 2014,2016,2018,2019
URL http://www.ccpem.ac.uk/courses.php
 
Description SCARF Annual Report 2016 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact A report was included in the annual report for the STFC SCARF computing facility. The report covered work with a CCP-EM user, in which data processing and structure determination was carried out using SCARF. As the computational demands of cryoEM grow, this exemplar showed how central computational facilities can help structural biologists.
Year(s) Of Engagement Activity 2016
URL http://www.scarf.rl.ac.uk/
 
Description S²C² CCP-EM Workshop 2020 
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 CCP-EM ran a virtual workshop over Zoom, 10-13 Nov 2020, hosted by the Stanford-SLAC Cryo-EM Center. We presented software for solving macromolecular structures by cryoEM to an audience of around 200 students. This is a larger number than we usually teach, which followed from it being an online event. This allowed us to reach more people, but we were unable to give direct attention to any individual student, for instance to help solve their own structure.
We were able to showcase CCP-EM software, including tools developed under the BBSRC grant BB/P000975/1.
The event allowed us to strengthen our ties with the Standford EM Centre, and the US community in general.
Year(s) Of Engagement Activity 2020
URL https://www.ccpem.ac.uk/training/s2c2_workshop_2020/s2c2_workshop_2020.php
 
Description Twitter feed about science 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact My twitter account has approximately 6.5 thousand followers. I use it to tweet mostly about science and science-related issues.
Year(s) Of Engagement Activity 2017,2018,2019,2020
URL https://twitter.com/SjorsScheres
 
Description Work experience students 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I hosted a work experience student from Year 10 at Didcot Girls School, for 2 weeks in summer 2017. She was asked to test and further develop a short Python script, applying machine learning to the classification of short peptides. She was also asked to investigate structural biology data, and report on it. I arranged visits for her to the Diamond and Octopus facilities, and to other research groups. The purpose was to encourage her interest in STEM subjects, and research as a career. Indirectly, she is expected to report her experience back to her peers at school, and hence raise the profile of research as a career at the school. The visit was arranged through the STFC Work Experience team, who reported positive feedback for the scheme as a whole. The scheme is heavily over-subscribed each year, and so is presumably seen as valuable by local schools.
I hosted a second work experience student for 1 week in summer 2018, this time a Year 11 student from Oxford. The format of the week was similar to the first student. The student showed a strong interest in machine learning for biological problems, and continued the project as part of a CREST Gold Award (submitted May 2019).
In 2019, I hosted another work experience student for 2 weeks, this time year 12. The project was an investigation of Javascript-based molecular viewers for displaying cryoEM structures.
Year(s) Of Engagement Activity 2017,2018,2019
URL http://www.stfc.ac.uk/about-us/work-with-us/work-experience/workexperienceral/
 
Description Workshop on Electron cryo-Microscopy and Molecular Dynamics 
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 workshop was held July 13-14th 2017 at the University of Leeds, and supported by CCP-EM and CCP-BioSim.

The first day was a hands-on workshop on the new software tool Fluctuating Finite Element Analysis (FFEA), which calculates dynamic trajectories for flexible biomolecules directly from cryo-EM/ET density maps. FFEA aims to provide an equivalent simulation tool for the EMDB as atomistic MD simulations have for the PDB. This approach uses volumetric meshes rather than atomistic co-ordinates as input such that it can model protein dynamics, protein-protein interactions, conformational switching between known configurational states and can be mapped back to atomistic co-ordinates, where these are available. This workshop is ideal for biomolecular simulators who would like to make full use of cryo-EM data in their modelling, or for experimentalists who would like to gain new theoretical insight into the dynamic behaviour of the structures they observe.

The second day explored the emerging computational techniques for achieving biological understanding from cryo-EM/ET images, and discussed areas most in need of further development. There were talks from speakers from the UK and Europe interested in the dynamics of biomolecules.

The 2-day meeting helped to build links between the experimental structural biology and molecular simulation communities.
Year(s) Of Engagement Activity 2017
URL http://www.ccpem.ac.uk/training/leeds_em_md_2017/leeds_em_md.php
 
Description YouTube 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talks from the CCP-EM Spring Symposia in 2015, 2016, 2017 and 2018 have been placed on YouTube using the STFC channel. Each edition gives around 10 hours of presentations covering the state of the art of electron cryo-microscopy. These are popular with those unable to attend the Spring Symposia in person, and also those wanting to refresh their memories.
Year(s) Of Engagement Activity 2015,2016,2017,2018
URL https://www.youtube.com/user/SciTechUK
 
Description the annual Icknield workshops 
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 first Icknield Workshop on Model Building and Refinement for High Resolution EM Maps was held at the RAL / Diamond campus, Harwell, UK on 2nd - 4th March 2016. The course was aimed at structural biologists with high resolution EM maps ready for / in the process of modelling, building and refinement. This three day course hosted some of the leading software developers and provided ample contact time to allow delegates to discuss their data in detail alongside traditional lectures and tutorials.

This is now an annual event, with further instances being held in April 2017, May 2018 and April 2019. The next installment is due to be held over 4 days in March 2020. There are typically 20-22 students, carefully selected in order to give a good coverage of cryoEM labs.
Year(s) Of Engagement Activity 2016,2017,2018,2019
URL https://www.ccpem.ac.uk/courses.php