BlueCryo Image Processing Computing Cluster

Lead Research Organisation: University of Bristol
Department Name: Biochemistry

Abstract

Imaging biomolecules at the molecular level to visualize their atomic details is essential to understand how they function in health and disease. Among the techniques capable of imaging biomolecules, electron cryo-microscopy (cryo-EM) has emerged as exceptionally powerful. New direct electron detectors, better microscopes and powerful processing software for the images recorded with this new hardware has led to a genuine revolution in cryo-EM. With these advances it is now possible to determine macromolecular structures at near-atomic resolution by cryo-EM, revealing essential molecular detail. High-resolution structural insight into molecular complexes, and also entire cells and even tissues, provide vital understanding of the molecular mechanisms of life.
Until recently, high-resolution cryo-EM was not possible in the South-West due to the lack of a suitable cryo-microscope. In 2017, we answer this unmet need by opening a South West Regional Facility for High-Resolution Cryo-EM at University of Bristol, equipped with state-of-the-art hardware. This will enable us to collect several terabytes of images or movies per day of successful data collection. To fully exploit the potential of this facility, and to maintain and increase our competitive posture, we must complement the state-of-the-art cryo-microscope with equally powerful high-performance computing (HPC) for image processing. Processing of the terabytes of images is so computation-intense that existing HPC infrastructure can by no means match the computation requirements of the new EM user community.
Therefore, to resolve this bottleneck, we ask here for funding of a computing cluster dedicated to image processing of cryo-EM data sets (BlueCryo). BlueCryo will enable researchers at University of Bristol to determine important structures by single particle cryo-EM and tomography, to interpret these structures using cutting-edge molecular modelling and to analyse the functional dynamics of the biological systems by state-of-the-art simulation methods. The BlueCryo HPC cluster will support the work of many researchers to accelerate their ambitious research, many of them funded by the BBSRC. The new resource will be instrumental for the discovery of new mechanisms of gene expression, to study protein transport into and across membranes, to understand the mechanism of secretion systems which play a crucial role in bacterial infections, and to illuminate a wide range of other important molecular processes responsible for biological function (and malfunction) in our cells. Moreover, the HPC cluster will critically support rational design of entirely novel proteins and peptide assemblies with tailor-made function, in vaccinology, drug delivery and drug discovery. Importantly, the new BlueCryo computing resource, together with the cryo-microscope, will further entice researchers from diverse life-science areas to partake in the cryo-EM revolution and generate new and exciting research synergies all across the South-West and beyond.
Our work has broad implications for multiple areas within the BBSRC remit including synthetic biology, basic bioscience underpinning normal human and animal health and infection. The projects cover areas of direct relevance to BBSRC remit and strategy. The proposal includes researchers with a strong track record of BBSRC funding. Early career researchers and a re-entry fellow are part of our team. Clearly, the computing cluster will not only decisively advance the research here proposed, and generate new programmes, synergies and collaborations. It will also enable us to engage in many other important scientific questions and to train new users and students. Thus, we expect to derive significant additional use in many areas of basic and applied research at University of Bristol, the South-West and beyond.

Technical Summary

State-of-the-art image processing for high-resolution electron cryo-microscopy (cryo-EM) is very computation-intense. High-performance computing clusters are required to efficiently analyse cryo-EM data sets and solve structures at near-atomic resolution in a reasonable time as well as for their interpretation by molecular modelling, e.g. using Rosetta, and molecular dynamics simulations.
In 2017, the new South-West Regional Facility for High-Resolution Cryo-EM will become operational at the University of Bristol (UoB), outfitted with a FEI Talos Arctica cryo-microscope, energy filter and a Gatan K2 Summit direct electron detector. It will also serve as a feeder instrument into the BBSRC-funded National Facility for Electron Cryo-Microscopy at Harwell with currently two Titan Krios cryo-microscopes. Thanks to automated data collection, terabytes of images and movies can be collected per day. These need to be analysed with efficient throughput to match the speed of data acquisition.
Current HPC resources at UoB cannot provide the required computation time, which is more than 100,000 cpu hours per project, alongside additional time for modelling and simulation for detailed structural interpretation. Therefore, we aim to implement a new cluster, BlueCryo, dedicated to image processing and cryo-EM structure interpretation. The cluster will have a GPU and a CPU component, with sufficient memory and disk space and will provide the equivalent of ~200,000 cpu hours per week. This will allow researchers at UoB (including many BBSRC-funded) to efficiently pursue their research on protein translocation across and into membranes, bacterial secretion systems, transcription factors, heart muscle filaments and target of rapamycin complexes as well as designed synthetic peptide assemblies for drug delivery vehicles and vaccines development. The interest to apply cryo-EM and image processing is paramount with many research groups keen to benefit from the cryo-EM revolution.

Planned Impact

The first and foremost impact of this proposal is the successful establishment of electron cryo-microscopy image processing at the University of Bristol (UoB). The proposed high-performance computing (HPC) cluster dedicated to image processing will decisively accelerate the ambitious research programmes pursued by leading researchers at the University. Moreover, the resource will enable many other laboratories to partake in the cryo-EM revolution, to advance their research and discovery.
The resource will furthermore enable us to develop new methodology to address key questions in the field leading to ample academic benefit beyond the ambitious research questions we address. Of note, the HPC cluster will be particularly instrumental to advance and consolidate the careers of early career and re-integrating researchers. Moreover, the proposed BlueCryo cluster will positively impact on the career development of the System Administrator employed to manage it, potentiated by the excellent support from Advanced Computing Research Centre (ACRC).
The individual research projects within the team possess significant potential for impact in the longer term. Our work addresses crucial questions which are at the core of biological function in prokaryotes and eukaryotes including humans. Our research programmes underpin our understanding of the healthy organism, disease-related changes and infection strategies used by pathogens. Work within the proposal seeks to generate new cellular effectors, versatile vehicles for drug delivery and next-generation vaccines by designing novel proteins and synthetic peptide assemblies. Through informing our basic understanding of essential cellular processes, it is most likely that our work will inform long-term projects in other fields reaching through to the discovery of new and better drugs in the pharma and biotech industries. Potential translational applications of our work will be identified from within the labs involved as well as by continuing liaison with our Research and Enterprise Department. Any outcomes of this work that are exploitable, notably in terms of intellectual property or knowledge transfer to the private sector, are handled by the highly experienced team within RED; who engage closely with funders such as BBSRC when appropriate.
The projects include considerable opportunity to train the researchers involved in areas that go beyond the day-to-day research methodology. Examples include our extensive integration with public communication and outreach programmes, the extensive network of University schemes to benefit the training and development of research staff (Bristol is at the forefront of research staff development). The environment as a whole at UoB is highly conducive to career development of our staff beyond academic, basic science research alone and thus contributes to the economic development of the nation.
The projects are all very data intensive and the management and analysis of such large (terabyte) datasets is applicable to many areas of professional life, outside of life science. In collaboration with the Bristol ACRC, the projects offer the researchers to develop and strengthen their capabilities in high-performance computing, script writing and bioinformatics; competencies which are high in demand on the job market.
This work will lead to significant image data that is readily used in both public understanding of science and artistic arenas. Through our public engagement plans and other outreach activities, this work therefore is likely to contribute to local exhibitions, promotions or displays as has been the case with previous work from the applicants' labs and others within UoB.

Publications

10 25 50
 
Description Key Results of the BlueCryo Project are:
(1) We successfully purchased and established BlueCryo, a high-performance computing resource for cryo-EM image processing and interpretation of resulting structures.
Following a competitive tender, BlueCryo was procured from OCF plc who carried out installation and initial provisioning over the summer of 2018. The resulting hardware solution consists of a management node, login node, fileserver node and 14 compute nodes. The compute nodes each provide 16 Xeon silver CPUs, 128GB RAM, 480GB SSD for local storage and 2 Nvidia V100 GPUs, all of which are connected by 10Gb network and supported by 400TB of scratch storage space. A "satellite" node providing an additional 16 CPUs, 128GB RAM, 40TB storage and a Nvidia P100 GPU forms a link between the Talos Arctica microscope and BlueCryo for initial data storage, pre-processing (using Relion 3.0 or Scipion 1.2) and automated streaming of data to user accounts on the cluster. Configuration of the BlueCryo cluster is now completed and we have a functioning cluster with a small but expanding user community. Available software tools will always be a continuing work in progress as new packages become available and users identify additional needs for their specific projects, but we have the major cryo-EM analysis tools available for use. Of particular note are Relion (versions 2.1 and 3.0) and Scipion 1.2 which are required by the vast majority of BlueCryo users, but cryo-ET tools have also been made available.
(2) The installations have been customised to suit requirements of our community with the aid of helpful conversations and meetings with the developers at CCPEM and I2PC respectively. A visit and conversations with staff at eBIC, and working very closely with the Bristol cryo-EM facility manager have also been instrumental in guiding how we have implemented best practice in our data management and real time data processing approaches. Training provision has thus far been on an individual or small group basis, tailored to individual needs. As our user base is expanding, a more formal introductory training course covering HPC, Linux, cryo-EM analysis approaches and specifics of using BlueCryo is currently being developed and will be run for the first time in 2019. We implemented BlueCryo as a system that mirrors the hardware and software setup at eBIC, allowing seamless transfer of data collected at eBIC.
(3) The BlueCryo HPC cluster is maintained and managed by Tom Batstone who is a dedicated Systems Administrator. Tom has been trained and is supported by the Advanced Computing Research Centre; he became a highly qualified member of stuff. Tom supports all BlueCryo users to familiarise with HPC computing and trouble shoots image processing software problems (see above and narrative impact).
(4) We now routinely utilise the BlueCryo cluster for single particle cryo-EM image processing of our diverse projects. Highlight cryo-EM projects from our labs include:
A 8 A cryo-EM structure of Target of Rapamycin (TOR) Complex 2 from Saccharomyces cerevisiae revealing for the first time the architecture of TOR Complex 2 (Karuppasamy et al, 2017).
A 6 A structure of the human 48S translation initiation complex bound to a capped messenger RNA (Eliseev et al., 2018)
A 3.5 A cryo-EM structure of the ADDomer, a designed virus-like particle derived from the penton base which is one of the capsid proteins of human Adenovirus 3 serotype. The publication describing the structure and molecular interactions that hold together this icosahedral particle is currently under review in Scientific Advances.
A 3.8 A cryo-EM structure of the D93K Thermosome mutant. The Thermosome is a class II chaperonin from the archaeon Thermoplasma acidophilum. In this mutant ATP hydrolysis is blocked in the ß subunit. A paper describing the mechanistic insights revealed through comparison of this structure and the wild-type is in preparation for Nat. Mol. Struct. Biol.
Furthermore, we have collected data of the bacterial holotranslocon and the FtsH protease membrane protein complex at eBIC. Both data sets are being processed on the BlueCryo HPC cluster.
Within the BBSRC-funded sLoLa project 'Development of supramolecular assemblies for enhancing cellular productivity and the synthesis of fine chemicals and biotherapeutics' (BB/M002969/1) the group of Paul Verkade has acquired and analysed cryo electron tomography data of isolated Bacterial Micro Compartments (BMC) and single particle data of one its fibre-forming components, PdUA. Both projects are in its finishing stages and publications are prepared for submission.
(5) Cryo-EM and image processing is now an integral part of current synthetic biology initiatives of the BBSRC-/EPSRC-funded BrisSynBio research centre to provide structures of synthetic proteins (mainly nanobodies) and their interactions with target proteins, de novo designed peptide assemblies and virus-like particles (the ADDomer) for drug delivery and vaccine development. Similarly, BlueCryo will underpin synthetic biology projects in the new Max-Planck Centre for Minimal Biology in Bristol (inaugurated in March 2019)
(6) As outlined in the narrative impact section, we provide training in image processing to the growing cryo-EM user community in Bristol and to educate the undergraduates (BSc and MSc level) and post-graduate students of the BBSRC-funded SWBio and BBSRC-funded Synthetic Biology Doctoral Training Programmes.
We have delivered cryo-EM image processing workshops and seminar series to support skills development of local, national and international researchers working in this fast-developing technique.
We widely disseminate our research and exciting new findings through public engagement activities - for example by School visits and Open Science days and by disseminating the images of the resulting cryo-EM structures.
(7) Danielle Paul and Christopher Woods have been awarded funding from the Alan Turing Institute to develop software tools for cryo-EM image processing. One of the main aims of the project is to widen the user base of the facility and cluster by opening up existing processing workflows to other biological systems. Project details are detailed on the Alan Turing Institute website under Danielle Paul's Fellowship page.

In summary, BlueCryo facilitates our cryo-EM work significantly in that it offers a computational infrastructure to manage and process the huge amounts (terabytes) of generated data. It ensures that the collected data can be immediately fed into a processing pipeline so that the delay between data collection and final output is shortened significantly. BlueCryo is easy to use, has an integrated support structure in the form of local staff (Tom Batstone) and online resources. BlueCryo also relieves research groups of the responsibility to acquire high-performance computers, since their processing-intensive work can be carried out on the cluster. Training in cryo-EM and image processing has now been implemented for students and postgraduate researchers, many of them are funded by the BBSRC. Thus, the GW4 Facility for High Resolution Electron Cryo-Microscopy and the BlueCryo HPC cluster are offering integrated solutions for cryo-EM experimental and computational work and provides ready access to our growing cryo-EM user community in the South West of UK.
Exploitation Route Over recent months, Tom Batstone our systems administrator helped Thomas Green from the HPC facility at the University of Cardiff with getting Relion setup on their systems, using experience and lessons learnt from BlueCryo. Moreover, Danielle Paul and Tom met with Tom Burnley (RAL, CCPEM) in December 2018 to discuss cryo-EM data analysis pipelines. Tom Burnley and Colin Palmer have kindly given us the beta code for Relion 'on the fly processing' (i.e. 'real-time' image processing during data collection) which is set-up and currently tested and optimised. Taken together, Bristol's BlueCryo HPC set-up is very interesting for other cryo-EM facilities as it is closely aligned with the setup at the national facility eBIC at Harwell.
Sectors Agriculture, Food and Drink,Digital/Communication/Information Technologies (including Software),Education,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://www.youtube.com/watch?v=l1HE1eL4jOQ
 
Description Training highly skilled individuals for the UK workforce: We have now implemented single particle cryo-EM and image processing into the teaching plan of the Biochemistry students in Year 3 as a 2 hours lecture and in the Masters of Science module 'Protein Assemblies and Molecular Machines as 3 hours lecture and a 2 hours hands-on initial training workshop with the ribosome as an example. Cryo-tomography became an integral part of the Year 3 Cell Biology lecture of Paul Verkade. We are constantly engaging in Staff training, i.e. postgraduates with expertise in structural biology, synthetic biology and biochemistry who want to solve high-resolution cryo-EM structures. In May 2018 we organised a 1-day Relion image processing workshop in Bristol, together with CCPEM. It offered image processing training to 32 postgraduates from UK, including students from the BBSRC South West Biosciences and the tripartite EPSRC/BBSRC Synthetic Biology Doctoral training programmes. Many of the participants are now using our GW4 cryo-EM facility and the BlueCryo computing cluster. In September 2018, Paul Verkade organized the EMBO practical course on Correlative Light and Electron Microscopy, including cryo-CLEM. Finally, postgraduates from our laboratories attended image processing workshops and meetings organised by CCPEM (e.g. February 2019: Relion 3 image processing workshop in Harwell, March 2019: Introduction to model building and refinement using cryo-EM maps in Madrid, April 2019: CCPEM user meeting in Nottingham). For the scientific community in Bristol, we regularly invite outstanding seminar speakers from the Cryo-EM field to give seminars. In September 2017 we organised the first Cryo-EM Symposium (speakers included John Briggs and Sjors Scheres from LMB Cambridge, Vicki Gold and Bertram Daum from MPI Frankfurt now University of Exeter). Finally, we have monthly user meetings, open to all members from GW4 universities, where postgraduates report on the progress of their cryo-EM projects. These meetings provide a platform for discussions about computational approaches as well as a way to talk about requirements and issues.In addition Tom Batstone and Danielle Paul run monthly meetings for the Blue-Cryo/HPC specific users, focused on the local needs and training of students and researchers using the cluster. We, together with the Bristol ACRC team and Christopher Woods, provided training for Tom Batstone who is systems administrator and responsible for BlueCryo which allowed him becoming a highly-qualified member of staff. In September 2018, Tom attended a Scipion workshop in Madrid which was attended by many service providers in the UK. They had extensive discussions about the best way to configure and use Scipion in the course of that and BlueCryo was, of course, a part of that. Tom Batstone is about to launch webpages detailing how to use the BlueCryo cluster, providing guidance on HPC and Linux and examples of specific data analysis workflows with details of how to run these on BlueCryo. Societal Benefit: Public Engagement: Societal benefits are through the multiple individual research projects that BlueCryo HPC enhances. An example is the ADDomer, a virus-like particle, where we were able to solve a 3.5 A cryo-EM structure which verified the design of the particle and allows additional improvements for application as a vaccine (publication currently under review in Scientific Advances). Furthermore, cryo-EM image processing presents an opportunity to showcase cutting-edge technology in Bioimaging and Computing to the public both from an information perspective as well as engaging young people in future science and (bio-)informatics careers. We have presented cryo-EM images at university recruitment days and at open days. The visual appeal of images and 3D structures from cryo-EM lends itself excellently to public engagement. In June 2018, Christopher Woods and Christiane Berger-Schaffitzel had a cryo-EM outreach session as well as BlueCryo logo competition together with OCF. We visited a local school in Southmead, a less privileged area of Bristol. 26 pupils from Year 6 attended. The winner of the BlueCryo logo competition visited the data centre to see the cluster in autumn 2018. Moreover, we set up a Twitter account (@GW4cryoEM) for the GW4 cryo-EM Facility & BlueCryo to disseminate updates and information. Our webpage is now uploaded and information on our cryo-EM and image processing infrastructure is available there (http://www.bristol.ac.uk/wolfson-bioimaging/equipment/cryo-em/). We have provided several tours of the cryo-microscope and data centre to visitors, most notably Lord Henley from Westminster House of Lords (October 2018). BlueCryo was used as an example of a specialist cluster for resolving specific computational issues then. We have had visits by the University of Bristol Advanced IT Board (chaired by Professor Nishan Canagarajah) in May 2018, and with the University of Bristol HPC executive committee (chaired by Professor Simon McIntosh-Smith). In November 2018, we presented BlueCryo to synthetic biologists at the EPSRC consortium meeting in Bristol (aimed to develop self-healing materials), organised by Nicolette Moreau and Paul Race; visitors were from UK universities and industry. Further Communication and Engagement: Research papers and new grants awarded are publicised through our own website as well as those of the department and university. Christiane Berger-Schaffitzel has given a number of presentations in the last two years, including EMBO practical courses (see engagement activities). She presented recently solved cryo-EM structures and also highlighted the new cryo-EM and BlueCryo image processing infrastructure. Ufuk Borucu who is responsible for the cryo-microscope has recently presented the cryo-EM research infrastructure to new PhD students of the EPSRC/BBSRC-funded SynBio CTD program, at the EM UK conference (Warwick, January 2019) and the SW EM meeting (Plymouth, March 2019), he will also attend the CCPEM meeting in Nottingham in April 2019. Danielle Paul has presented data collected in the cryo-EM facility and processed on BlueCryo at the Academy of Medical Sciences Winter meeting 2018, Jean Golding Institute Showcase 2018, International Microscopy Conference in Sydney 2018 and the British Heart Foundation Fellows meeting 2017. Patient groups, health care professionals, fundraisers and general public were present at the British Heart Foundation Fellows meeting where DP presented in 2017. Economic Impact, Exploitation and Application: The ADDomer VLP (mentioned above) is a collaborative project with Imophoron Ltd, founded in Bristol in 2018 (https://unitdx.com/novel-vaccine-technology-interview-fred-garzoni-imophoron/). Cryo-EM structures of the designed virus-like particles support the development of new vaccines. A further company, founded by Dek Woolfson, investigates superstructure arrays formed by alpha helical barrels with defined pore sizes to generate artificial sensors. The barrels arrays can be quality controlled by EM. Many other projects are at a "pre-competitive" stage in terms of commercial exploitation. The bacterial holo-translocon project aiming at a high resolution cryo-EM structure of the active translocation machinery is accompanied by an on-going drug discovery programme (by Ian Collinson and Dr A. Woodland, Drug Discovery Unit, Dundee) aimed at the identification of small molecule inhibitors of the bacterial translocation machinery.
First Year Of Impact 2017
Sector Education,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description 'Academic Lead' of the South West Regional Facility for High-Resolution Electron Cryo-Microscopy, Bristol
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
Impact We made significant changes in the organisation of the facility. We are in the process of improving visibility, efficiency and effectiveness of usage of microscope time and computing resources.
 
Description Appointed Member of the 'Wellcome Trust Dynamic Molecular Cell Doctoral Training Program Management Group'
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
 
Description Appointed Member of the BBSRC-funded SWBio Doctoral Training Program Management Group
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
 
Description Biochemistry Management Group, School of Biochemistry, Univ. of Bristol
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
 
Description Chair of Steering Committee, GW4 Regional Facility for High-Resolution Electron Cryo-Microscopy, Bristol (2017-2018)
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Participation in a advisory committee
 
Description Teaching postgraduate students, EMBO practical courses (as tutor and speaker) (since 2008)
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
 
Description BBSRC-funded BrisSynBio second-wave project, Co-Investigator
Amount £250,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2016 
End 03/2019
 
Description BBSRC-funded SWBio DTP Studentship, 'Molecular Mechanisms of SMG1 Kinase in Health and Disease' to Alvin Szeto;
Amount £100,000 (GBP)
Funding ID 2117369 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2018 
End 08/2022
 
Description Chinese Scholarship Council Studentship, 'Mechanisms of SMG1 Kinase Activation and Regulation', to Jiayi Fu
Amount £100,000 (GBP)
Organisation University of Leeds 
Department China Scholarship Council
Sector Academic/University
Country United Kingdom
Start 09/2018 
End 09/2021
 
Description MRC research grant, Co-Investigator
Amount £2,080,000 (GBP)
Funding ID MR/P019471/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 05/2017 
End 04/2022
 
Description Oracle Higher Education and Research programme, enabling Cryo-EM image processing using Oracle's high-performance public cloud infrastructure; (https://www.oracle.com/uk/industries/higher-education/)
Amount £10,000 (GBP)
Organisation Oracle Corporation 
Sector Private
Country Global
Start 06/2018 
End 12/2018
 
Description South West Regional Facility for High-Resolution Electron Cryo-Microscopy
Amount £1,000,000 (GBP)
Funding ID 202904/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2016 
End 01/2021
 
Description Wellcome Trust Investigator Grant, 'Structure and Mechanism of Key Nonsense-Mediated mRNA Decay Factor Complexes'
Amount £1,514,695 (GBP)
Funding ID (210701/Z/18/Z) 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2018 
End 09/2023
 
Description Wellcome Trust Multi-User Equipment Grant, 'Expanding the capabilities and use of the South West Regional Facility for High-Resolution Electron Cryo-microscopy' (Co-I)
Amount £1,000,000 (GBP)
Funding ID (206181/Z/17/Z) 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2016 
End 11/2021
 
Description Cystic Fibrosis Foundation Workshop on Nonsense Readthrough, Bethesda, Maryland, USA, invited speaker (22-23 January 2019) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Supporters
Results and Impact Research Seminar and workshop, reporting about our recent work on protein quality control mechanisms, presenting and advertising the new GW4 Cryo-EM infrastructure in Bristol. Presentation sparked questions and discussion afterwards, invitation to future meetings and plans for future collaborations. The workshop was organised by the Cystic Fibrosis Foundation; the ca 60 participants were from charities, industry and academia (about one third each).
Year(s) Of Engagement Activity 2019
 
Description EMBO Practical Course "High throughput methods for protein production and structural analysis" at Diamond and the Research Complex at Harwell, invited speaker (10.-19.6.2019) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I am going to present our work on membrane protein complex production and new cryo-EM structures. I will represent the GW4 Facility for High-Resolution Cryo-EM and advertise our Cryo-EM infrastructure and image processing infrastructure, with the intent to spark interest in this research area and the techniques.
Year(s) Of Engagement Activity 2019
URL http://meetings.embo.org/event/19-protein-production
 
Description EMBO Practical Course "Small angle neutron and X-ray scattering from proteins in solution", Grenoble, France, invited speaker 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I presented the use of cryo-EM and image processing to address biological questions and advertised the new cryo-EM and BlueCryo image processing capabilities in Bristol. I presented the cryo-EM structure of the holo-translocon and discussed its functions in membrane protein integration, folding and protein complex assembly. The presentation sparked excellent discussions with the students about membrane protein complexes, cryo-EM and image processing.
Year(s) Of Engagement Activity 2017
URL http://meetings.embo.org/event/17-small-angle-scattering
 
Description EMBO Practical Course "Small angle neutron and X-ray scattering from proteins in solution", Grenoble, France, invited speaker (24.09.2019) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I am going to present our work on membrane protein complex production, characterisation and new cryo-EM structures. I will represent the GW4 Facility for High-Resolution Cryo-EM and advertise our Cryo-EM infrastructure and image processing infrastructure, with the intent to spark interest in this research area and the techniques.
Year(s) Of Engagement Activity 2019
URL http://meetings.embo.org/event/19-small-angle-scattering
 
Description Faculty of Biology, Medicine and Health, University of Manchester, invited seminar speaker 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Research Seminar. I presented our recent cryo-EM structure of the human 48S initiation complex and our holotranslocon project.
I represented the GW4 Facility for High-Resolution cryo-EM and advertised our cryo-EM and image processing infrastructure. I sparked interest in this research area and the techniques, we had good discussions and made plans for future collaboration.
Year(s) Of Engagement Activity 2018
URL http://events.manchester.ac.uk/event/event:o1hn-jnlm6bty-ynvpil/protein-and-rna-fate-seminar-christi...
 
Description GW4's Great West Research and Innovation Day, Bath, invited speaker (1st November 2017) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact I presented our research questions and the new GW4 Facility for high-resolution cryo-EM as well as the image processing facilities. The audience comprised representatives from industry, politics and university leaders. I advertised our research, raised awareness of our new shared resources funded by Wellcome Trust Multi-User Equipment grants and by the BBSRC Alert scheme.
Year(s) Of Engagement Activity 2017
URL http://gw4.ac.uk/news/gw4-vision-unveiled-regional-showcase-event/
 
Description Lord Henley from Westminster House of Lords, Visiting the Electron Cryo-Microscopy Facility 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact 25/10/2018 : Lord Henley visited to learn more about ongoing Synthetic Biology at Bristol, Part of the visit was a tour in the GW4 Facility for high-resolution Cryo-EM. We explained to him the importance of Cryo-EM and state-of-the-art image processing which provide structures for vaccine development and drug design .
Year(s) Of Engagement Activity 2018
URL http://www.bristol.ac.uk/news/2018/october/lord-henley.html
 
Description Novozymes Prize Symposium "Protein Folding on the Ribosome", Stockholm, Sweden, invited speaker 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Research Seminar, reporting about our recent work on protein quality control mechanisms, presenting and advertising the new GW4 Cryo-EM infrastructure in Bristol. Presentation sparked questions and discussion afterwards, and invitation to future meetings.
Year(s) Of Engagement Activity 2018
URL https://cotranslationalfolding.wordpress.com/programme/
 
Description Organisation of the Opening Symposium of the GW4 Regional Facility for High-Resolution Electron Cryo-Microscopy (September 1st, 2017) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Around 200 researchers, students, officials (Deans, Vice-Chancellors) from the GW4 universities, representatives from BBSRC, Wellcome Trust, and industry (GSK) joined the opening symposium of the GW4 Regional Facility for High-Resolution Electron Cryo-Microscopy in Bristol. The aim of the event was to make the researchers and the public aware of the new cryo-EM facility and image processing capabilities and the exciting possibilities offered by this new technology. There is clearly increased interest in the use of cryo-EM and image processing to answer biological questions. -- https://twitter.com/hashtag/GW4cryo?src=hash. http://gw4.ac.uk/news/gw4-alliance-unveil-cutting-edge-microscopy-facility/
Year(s) Of Engagement Activity 2017
URL http://gw4.ac.uk/shared-facilities/
 
Description Organisation of the first GW4/CCPEM Relion Image Processing Workshop, University of Bristol (18th May 2018) 
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 I organised this workshop in collaboration with CCPEM and GW4 to train new users of cryo-EM and image processing , i.e. to help familiarise with the new technique and software packages. We meet with this workshop the increased demand of training in this technology (evidenced by 10-fold over-subscription of these type of training events). We accepted 32 participants , 30 from UK, 2 from EU countries, 4 from UK industry (GSK , Heptares, UCB Pharma).
The workshop provided a networking opportunity enabling new/ outside users to access the equipment, and brought together scientists with diverse background sparking interesting discussions and increased interest in cryo-EM usage.
Year(s) Of Engagement Activity 2018
URL http://www.ccpem.ac.uk/courses.php
 
Description School Visit at Horfield CEVC Primary School, Bristol BS10 5BD 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 09.07.2018: 'BlueCryo Project and drug development' at Horfield CEVC Primary School, Bristol BS10 5BD, (with Christopher Woods and Georgina Ellis, OCF plc). We visited the Horfield school and together with a local school teacher for Science organised a workshop on vaccine development and the role of Electron Cryo-Microscopy and Image processing.
OCF contributed a price for the pupil contributing the best Blue Cryo Logo. 26 Participants from Year 6. ----- Please see the extract below from this weeks Horfield Newsletter: "Year 6 Science Workshop with The University of Bristol On Monday afternoon 26 children from Year 6 took part in a science and computing workshop. Two scientists from the University of Bristol taught us all about vaccines and viruses as strange as the Chikungunga virus. I asked six Year 6s to tell me about their experience during the afternoon and this is what they said. Tom: "They may be able to find a vaccine against skin cancer. They can also create 3D images of viruses." Zoe: "I enjoyed learning about how they flash-freeze chemicals and viruses so that they can look at them closely using an electron microscope." Fletcher: "I learnt how to design a logo using Microsoft Paint and I learnt a lot about Blue-Cryo (the name of the supercomputer at Bristol University) and electron microscopy." Ruth: "You had to create a logo for Blue-Cryo and the winner with the most attractive logo won a 10" tablet." Olivia: "In three words I would describe the workshop as entertaining, interesting and challenging." Melissa: "I found the image processing game that we did in the workshop relatively hard; the hardest bit was choosing between a knot, ball or ring shaped molecule." Overall, I think every Year 6 who took part enjoyed spending their afternoon with two inspirational scientists. Congratulations to Antoine for winning the competition"
Year(s) Of Engagement Activity 2018
 
Description South West Structural Biology Annual Meeting, Cardiff, Plenary Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact I gave a Plenary Lecture about the new, shared Cryo-EM and BlueCryo Image Processing capabilities at the South West Structural Biology Annual Meeting in Cardiff. I thus raised awareness of the new facilities and increased the interest in applying electron cryo-microscopy to address biological questions. In addition, I presented our holotranslocon project. The presentation sparked excellent scientific discussions about membrane protein expression in bacteria versus vertebrates as well as the limits of X-ray and cryo-EM in structural biology.
Year(s) Of Engagement Activity 2017
URL https://www.cardiff.ac.uk/conferences/south-west-structural-biology-consortium-2017
 
Description invited seminar speaker, Francis Crick Institute, London, 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Research Seminar, reporting about our recent Cryo-EM structure of TORC2 from S. cerevisiae, presenting and advertising the new GW4 Cryo-EM infrastructure in Bristol. The presentation sparked questions and discussion afterwards and plans for future meetings were made.
Year(s) Of Engagement Activity 2018
URL http://lists.cryst.bbk.ac.uk/pipermail/lsbc/2018-February/000358.html