BlueCryo Image Processing Computing Cluster

Lead Research Organisation: University of Bristol

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

publication icon
Bradshaw M (2019) After the revolution: how is Cryo-EM contributing to muscle research? in Journal of muscle research and cell motility

publication icon
Bárcena M (2021) Structural biology in the fight against COVID-19. in Nature structural & molecular biology

publication icon
Hutchins GH (2023) An expandable, modular de novo protein platform for precision redox engineering. in Proceedings of the National Academy of Sciences of the United States of America

 
Description The most significant achievements 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, Relion 3.1) 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 an expanding user community (currently 42 users). 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.

(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 the national facility eBIC (Harwell) 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. More formal introductory training courses covering HPC and Linux are available via the University of Bristol HPC team. We implemented BlueCryo as a system that mirrors the hardware and software setup at the national facility eBIC, allowing seamless transfer of data collected at eBIC or in the GW4 cryo-EM facility. Automated on-the-fly processing has been implemented to allow adjustment of data collection based on an initial quality assessment of the images.

(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 staff. Tom supports all BlueCryo users to familiarise with HPC computing, maintains the system and trouble-shoots image processing software problems.

(4) A management structure is in place, with a BlueCryo Steering Group that meets about 3-times per year. The Cryo-EM User group comprising all students, PDRAs and PIs interested in cryo-EM, meets on a monthly basis. Moreover, there is a management meeting every two weeks between Tom Batstone and Alan Cheung (PI, School of Biochemistry) to discuss usage, software issues and other tasks at hand.

(5) 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:
The Schaffitzel lab published (i) a 8 Å 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, Nat. Commun. 2017). (ii) A 6 Å structure of the human 48S translation initiation complex bound to a capped messenger RNA (Eliseev et al., Nucl. Acids Res. 2018). (iii) In collaboration with the Berger lab, a 3.5 Å 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, was published (Vragniau et al., Science Advances 2019). (iv) During lockdown in March 2020, Cryo-EM and the BlueCryo cluster were used by the Berger and Schaffitzel groups to solve the 2.85 Å structure of the SARS-CoV-2 spike glycoprotein. The Spike cryo-EM structure led to the discovery of a free fatty acid-binding pocket which is occupied by linoleic acid (Toelzer et al., Science 2020). This publication achieved an altmetric attention score of 1478, placing it in the top 5% of all research outputs scored by Altmetric. (v) Currently, a manuscript describing cryo-EM structures of human translating ribosomes with an antibiotic revealing the molecular mechanisms of inhibition of protein synthesis by this antibiotic is in preparation (Powers et al., to be submitted).
(vi) A 3.8 Å cryo-EM structure of the D93K Thermosome mutant has been solved. 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 (Paul lab). (vii) Furthermore, Danielle Paul's team is investigating the molecular basis of heart disease via the structural analysis of isolated filamentous cardiac proteins (Bradshaw and Paul, 2019). The analysis of this phase plate data collected at eBic is carried out on BlueCryo, sub-nanometre structures of native filaments have been calculated for the first time.
(viii) In 2019, high resolution tomographic data from the Dodding lab was processed on BlueCryo. The images were of hap1 cells treated with a small molecule which caused a substantial rearrangement of the cytoskeleton and the ability to visualise actin filaments inside microtubules for the first time. The publication describing this remarkable discovery (Paul et al., J. Cell Biol. 2019) has achieved an altmetric attention score of 84, placing it in the top 5% of all research outputs scored by Altmetric.
(ix) Ross Anderson's group used BlueCryo to solve the cryo-EM structure of a de novo designed multi-hem protein (Hutchins et al., BioRXiv; doi: https://doi.org/10.1101/2020.09.24.311514).
(x) 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-tomography data of isolated Bacterial Micro Compartments (BMC) and single particle data of one its fibre-forming components, PdUA, and published results in Nat. Communications (Lee MJ, Mantell J et al., 2018) and Microbiology Open (Juodeikis et al., 2020).
(xi) The group of Ian Collinson collected and processed cryo-EM data sets for the bacterial holo-translocon, a seven membrane protein complex. The structure of the holo-translocon with the beta-barrel assembly machinery (BAM) complex was recently published in ELife (Alvira et al., 2020).

(6) Cryo-EM and image processing became an indispensable and integral part of current synthetic biology initiatives of the BBSRC-/EPSRC-funded BrisSynBio research centre to provide structures of synthetic proteins and their interactions with target proteins, de novo designed peptide assemblies and virus-like particles (e.g. 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)

(7) 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 Doctoral Training Programme and the EPSRC/BBSRC-funded Synthetic Biology Doctoral Training Programme. We deliver cryo-EM image processing workshops and seminar series to support skills development of local, national and international researchers working in this fast-developing technique (e.g. Relion image processing workshops). Sara Alvira (School of Biochemistry) was awarded funding for a GW4 Cryo-EM seminar series from the Biochemical Society; we invite early career researchers/young PIs to present their cryo-EM research.

(8) We widely disseminate our research and exciting new findings through public engagement activities - for example by interviews, presentations to the general public and pupils (e.g. UKRI School of tomorrow, EC FUTURES2020 public festival), school visits and Open Science days and by disseminating the images of the resulting cryo-EM structures.

(9) 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 applying ML methods for automated protein detection to widen the user base of the cryoEM facility and BlueCryo cluster by opening up existing processing workflows to other biological systems. (Cermal et al. 2020). Project details are described on the Alan Turing Institute website under Danielle Paul's Fellowship page. Data from BlueCryo was used in the Inaugural Turing Institute network Data Study Group.

In summary, BlueCryo is an integral and indispensable part of our research using cryo-EM in that it offers a computational infrastructure to manage and process the huge amounts (terabytes) of generated data. Implementation of pre-processing and automated data transfer from the point of collection ensures that the collected data can be immediately fed into a processing pipeline so that the delay between data acquisition and final output is shortened significantly. BlueCryo is easy to use, has an integrated support structure in the form of local staff (Tom Batstone), online resources and monthly user meetings and clinic sessions to discuss future requirements and improvements. BlueCryo also relieves research groups of the responsibility to acquire, install and maintain 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, for instance by the BBSRC-funded SWBio DTP. 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 Tom Batstone, our systems administrator, helped Thomas Green from the HPC facility at the University of Cardiff with setting up Relion on their systems, using experience and lessons learnt from BlueCryo (2019). Moreover, Danielle Paul and Tom Batstone 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 now set-up in the GW4 cryo-EM facility. 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. In addition, the BlueCryo cluster is used for training and teaching purposes, such as the GW4/CCPEM Relion image processing course(s) - the first workshop in 2018 was oversubscribed, the 2nd workshop on Relion3.1 was scheduled on 25th June 2020, but had to be postponed due to lockdown.
Sectors 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 (1) 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. Schaffitzel teaches cryoEM and image processing in Year 3 (2 hours lecture), in the Masters of Science programme 'Biophysics and Molecular Life Sciences' (1 hour lecture), and in the Masters of Science module 'Protein Assemblies and Molecular Machines' (3 hours lecture plus 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-funded SWBio Doctoral Training Programme and the tripartite EPSRC/BBSRC-funded Synthetic Biology DTP. 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. Both events, the GW4/CCPEM Relion image processing workshop and the EMBO practical course, were to be offered again in June 2020 and September 2020 respectively. However, these events had to be postponed due to Covid-19 lockdown and restrictions. 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 and April 2020: CCPEM user meeting in Nottingham). In 2023, Paul Verkade obtained additional funding to organise a Gordon Research Conference on Volume EM, in addition to the EMBO course for correlated light and electron microscopy. For the scientific community in Bristol, we regularly invite outstanding seminar speakers from the Cryo-EM field to give seminars, e.g. Tom Rapoport (Harvard), Bonnie Murphy (MPI Frankfurt), Thomas Meier (Imperial College London), Anthony Roberts (Birkbeck College London) and Stefan Raunser (MPI Dortmund), Paula da Fonseca (Glasgow). 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). In 2020, Dr Sara Alvira-de-Celis (Collinson group) was awarded funding from the Biochemical Society to organise a GW4 seminar series on cryoEM. Invited speakers included Basil Greber (ICR London), Ben Engel (Helmholtz Zentrum München. Munich. Germany), Cristina Paulino (University of Groningen. The Netherlands) and Giulia Zanetti. (ISMB. Birkbeck. University of London). In 2023, we invited Xiaodong Zhang (Imperial College, London), Mark Young (Cardiff University) and Guillermo Montoya (Novo Nordisk Research Centre, Copenhagen, Denmark) for cryo-EM seminars. Finally, we have monthly Blue-Cryo user meetings, open to all members from GW4 universities, where students and postdocs report on the progress of their cryo-EM projects. These meetings provide a platform for discussions about computational approaches, trouble shooting as well as a way to talk about software requirements and other issues. In addition, Tom Batstone (HPC team) and Danielle Paul organise meetings for BlueCryo/HPC users, focused on the local needs and more individual training. 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. Dr Burak Kabasakal, working in the Schaffitzel lab as BBSRC-funded PDRA, has accepted position as group leader for structural biology at University of Ankara, Turkey to establish Electron Cryo-Microscopy. (2) Societal Benefit: Public Engagement: Societal benefits are through the multiple individual research projects that BlueCryo HPC enhances. A prominent example with health impact 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 ADDomer application as a vaccine (Vragniau et al. Science Advances 2019). This publication attracted significant attention from the media, with 30+ news and views articles, features and interviews published to date (see other outputs and knowledge section). A further key example is the Cryo-EM structure of the SARS-CoV-2 spike glycoprotein; Berger and Schaffitzel teams discovered a previously unknown pocket within in the protein. Surprisingly, inside of the pocket, we found a small molecule. Using mass spectrometry (LC-ESI-TOF and LC-MS/MS) we could show that this small molecule was linoleic acid. With the help of Andrew Davidson (Univ. of Bristol), a renowned coronavirus expert, and his team, they could show that binding of linoleic acid to the spike protein blocks virus replication. Thus, Berger and Schaffitzel teams discovered a druggable pocket in the SARS-CoV-2 spike protein. Moreover, this pocket is occupied by a potential drug, linoleic acid, that binds the pocket with high affinity and high specificity. This finding was published in Science (Toelzer et al., 2020) and attracted significant attention: interviews for BBC point west, BBC breakfast, Radio stations, Bristol Post (Schaffitzel was named 'coolest person in Bristol 2020' in recognition of the Covid-19 research efforts), Bristol Magazine, Science Podcast, altogether the publication was picked up by 142 news outlets (Altmetric score 1589, which places this publication into the top 1% of publications published at the same time). Schaffitzel, Berger and Toelzer received invitations for webinars, conferences, and workshops (CCPEM workshop on Cryo-EM validation; young scientist keynote at PEGS conference 2021, FEI Webinar, etc.). Schaffitzel also presented this Covid-19 research at the EC Futures2020 festival (Nov 2020) and the University of Bristol staff meeting (600 participants) (Dec 2020). In March 2022 and March 2023 the cryo-EM structure and discovery of a druggable pocket in SARS-CoV-2 spike was showcased at the offer holder visit day where pupils and their parents visit the school of Biochemistry. 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 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. In February 2021, they repeated the event as an online workshop at the UKRI School of Tomorrow (400 pupils and teachers attended). 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/). 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. We have provided several tours of the cryo-microscope and data centre to visitors, most notably to Lord Henley from Westminster House of Lords (October 2018), to Andreas Michaelis, German Ambassador, London during his visit in Bristol (October 2020) and to the new German Ambassador in London, Miguel Berger who visited 14th November 2022. (3) 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. 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 BBSRC- and WT-funded 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), and attended the CCPEM meeting in Nottingham in April 2019. In addition, he has attended the Drug Discovery 2019 conference in Liverpool in November 2019 to network with industrial partners. More recently, Schaffitzel presented Covid-19 related research at the 9th International Singapore Lipidomics Symposium (March 2021), at a Webinar organised by Thermo Fischer Scientific (Dec 2020), at a Focus webinar about Digital Biology organised by the Biochemical Society (Nov 2020) and at the CCPEM, UK EM Validation Network online Symposium (Nov 2020). Further presentations are planned for 2022 at the CCPEM user meeting (Nottingham) and the GERLI meeting in November in France (Cap Ferrat). Danielle Paul was asked to talk about how BlueCryo is used to process cryo-EM data at the regional HPC symposium held in Bristol in Sept 2019 and has presented data collected in the cryo-EM facility and processed on BlueCryo at Diamond in February 2020, the launch of the Elizabeth Blackwell Institute Data Health Strand Oct 2019, The Turing Institute Molecular Biology workshop July 2019, 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. Data processed on BlueCryo formed the basis of a Turing Institute Data Study Group challenge in August 2019. The challenge was open to data scientists from across the world and a team of 8 participants used novel data analysis techniques to identify proteins in the image. It was the first time that a Data Study Group was held at an external Turing partner institute. The participants were given a tour of the GW4 cryo-EM facility and were shown the image processing workflow implemented on BlueCryo. (4) Economic Impact, Exploitation and Application: The ADDomer virus-like particle (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. Rosa Biotech (https://www.rosabio.tech/), a 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. The discovery of a druggable pocket in spike protein has motivated many groups to search for potential antivirals that could target that pocket. It further has justified using linoleic acid for outpatient treatment of Covid-19 patients in USA (Case Study Using Nebulized Isomerized Linoleic Acid (LA) for Outpatient Treatment of Symptomatic COVID-19. - Abstract - Europe PMC; Symptom Duration Shortened by Early Initiation of Nebulized Isomerized Linoleic Acid (LA) for Outpatient Treatment of COVID-19. by Sven Jonsson, Caroline Jonsson :: SSRN). However, these reports are with a small number of patients, Linoleic acid is not FDA-approved, and therefore the results need to be verified in proper clinical trials. With Adam Finn in the Bristol Medical School, Berger, Schaffitzel and colleagues designed a clinical trial (Phase I/IIa) to use free fatty acids binding to the pocket in spike protein as Covid-19 antivirals. Halo Therapeutics was funded to finance and promote the efforts to develop Pan-Coronavirus Antivirals (https://halo-therapeutics.com/ and https://www.linkedin.com/company/halotherapeutics/ ).
Sector Education,Healthcare,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 (2018-present)
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 Committee member of the Royal Society & Wellcome Trust Sir Henry Dale Fellowship Interview Committee (SHDFIC). C Berger-Schaffitzel, 2021
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
Impact The Sir Henry Dale fellowship scheme is a partnership between the Royal Society and the Wellcome Trust. It supports research ranging from molecules and the cells vital to life, to the spread of diseases and vectors of disease around the world, to public health research. It supports young researchers who have made important contributions to your area of research. C Berger-Schaffitzel was co-opted member of the evaluation panel in 2020 and appointed member in 2021
URL https://royalsociety.org/grants-schemes-awards/grants/henry-dale/
 
Description Appointed Committee member of the Wellcome Trust Career Development Award Interview Committee
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
 
Description Appointed Member of Diamond Peer Review Panel, panel 12 covering eBIC and B24, Harwell, UK (05/2019-11/2021)
Geographic Reach Europe 
Policy Influence Type Participation in a guidance/advisory committee
Impact I am appointed member of the peer review panel 12 responsible for distribution of access to the national facility for Electron Bio-Imaging Centre (eBIC) and beamline 24 (including X-ray tomography). The panel ensures fair and transparent distribution of access to the high-end research infrastructure available at Diamond, Harwell, enabling cutting-edge research.
 
Description Appointed Member of the 'Faculty Research Facilities Management Group', Faculty of Life Sciences, Univ. of Bristol
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
 
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 Advisory Network of the Schering Stiftung, Berlin, Germany (Since 05/209)
Geographic Reach Europe 
Policy Influence Type Participation in a guidance/advisory committee
URL https://scheringstiftung.de/en/stiftung/advisorynetwork/
 
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 Appointed member of the iNEXT Horizon 2020 - Discovery Advisory Panel
Geographic Reach Europe 
Policy Influence Type Participation in a guidance/advisory committee
Impact iNEXT brings together structural biology facilities for X-rays, NMR, cryo-EM and macromolecular biophysics, and aims to make them accessible to new user communities, to develop the methods further through joined research efforts, and to offer better integration between scientific fields and within the field of structural biology through scientific meetings, practical courses, and training workshops. A major aim of iNEXT-Discovery is providing access to users from the European Union and all associated countries, to all participating facilities. Importantly, it aims to not only make available state of the art instruments, but also make available to all users expert support, to help non-experts answer exciting scientific questions.
URL https://inext-discovery.eu/network/inext-d/networking
 
Description Asked to represent Bristol at BBSRC data Intensive Bioscience meeting
Geographic Reach National 
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 Case Study for the Academy of Medical Sciences
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
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 guidance/advisory committee
 
Description Jury Member of the 'Friedmund Neumann Prize 2020' Schering Stiftung (Foundation), Berlin, Germany (03/2020)
Geographic Reach Europe 
Policy Influence Type Participation in a guidance/advisory committee
URL https://scheringstiftung.de/en/programm/lebenswissenschaften/nachwuchsfoerderung/friedmund-neumann-p...
 
Description Jury Member of the 'Friedmund Neumann Prize 2021' Schering Stiftung, Berlin, Germany
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
URL http://scheringstiftung.de/en/programm/lebenswissenschaften/friedmund-neumann-preis/
 
Description Member, Wellcome Trust Multi-user Equipment Committee for 2020, C. Berger-Schaffitzel
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
Impact Multi-user Equipment Grants offer up to five years of support for the purchase or installation of state-of-the-art instruments which fuel cutting edge research. C Berger-Schaffitzel was co-opted member of the evaluation panel.
URL https://wellcome.org/grant-funding/schemes/multi-user-equipment-grants
 
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 BrisEngBio Proof of Concept award. Megabody in vitro selection and engineering for cryo-EM structure analysis of FFAR1-bound lung fibrosis drugs to treat long COVID
Amount £50,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 11/2022 
End 10/2023
 
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 08/2018 
End 08/2022
 
Description BBSRC/EPSRC funded BrisSynBio Centre Bristol, Big Ideas in Biodesign
Amount £70,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2018 
End 03/2019
 
Description BHF PhD Studentship no. FS/20/5/34973 "High resolution structural studies of cardiac thin filaments; heart disease at the molecular level"
Amount £111,301 (GBP)
Funding ID FS/20/5/34973 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2020 
End 05/2023
 
Description Biotechnology and Biological Sciences Research Council (BBSRC)-funded SWBio doctoral training programme studentship
Amount £100,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2020 
End 08/2024
 
Description Career Re-Entry Fellowship Extension
Amount £70,625 (GBP)
Funding ID FS/14/18/30711 
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2020 
End 08/2023
 
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 08/2018 
End 09/2021
 
Description Costed Extension to AMS Springboard award
Amount £7,619 (GBP)
Funding ID SBF003\1142 
Organisation Academy of Medical Sciences (AMS) 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2021 
End 10/2021
 
Description Electron cryo-microscopy of SARS-CoV-2 spike protein variants and the ADDomer-SARS-CoV-2
Amount £12,884 (GBP)
Organisation University of Bristol 
Sector Academic/University
Country United Kingdom
Start 04/2020 
End 09/2020
 
Description MRC research grant, Co-Investigator
Amount £2,080,000 (GBP)
Funding ID MR/P019471/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2017 
End 04/2022
 
Description Novel platforms to develop polyspecifically-effective, safe, affordable and thermostable monoclonal camelid VHH nanobodies to treat snake venom-induced necrosis in India and sub-Saharan Africa
Amount £4,000,000 (GBP)
Funding ID 221708/Z/20/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2021 
End 03/2025
 
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 £30,000 (GBP)
Organisation Oracle Corporation 
Sector Private
Country United States
Start 05/2018 
End 12/2021
 
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 Springboard scheme round 3
Amount £99,952 (GBP)
Funding ID SBF003\1142 
Organisation Academy of Medical Sciences (AMS) 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2018 
End 03/2020
 
Description Turing Fellow Project
Amount £110,567 (GBP)
Organisation Alan Turing Institute 
Sector Academic/University
Country United Kingdom
Start 03/2019 
End 02/2021
 
Description Turing Pilot Research Grant via Exeter Institute for Data Science and Artificial Intelligence (IDSAI) Automated Identification of protein filaments in high-resolution 3D imaging data 6 months funding for a research software engineer.
Amount £20,000 (GBP)
Organisation Alan Turing Institute 
Sector Academic/University
Country United Kingdom
Start 06/2022 
End 01/2023
 
Description Up-frameshift protein interactions in translation termination and nonsense-mediated mRNA decay
Amount € 212,933 (EUR)
Funding ID 101024558 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 03/2022 
End 02/2024
 
Description Wellcome Trust - University of Bristol institutional Translation Partnership Award
Amount £79,263 (GBP)
Funding ID fEC282839 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2020 
End 02/2021
 
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 09/2018 
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
 
Title Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein 
Description When we analysed the atomic structure of the SARS-CoV-2 Spike glycoprotein, we discovered a previously unknown hydrophobic pocket within in the protein. To our surprise, inside of the pocket, we found a small molecule. It turned out that this small molecule was linoleic acid. With the help of Andrew Davidson and his team, we could show that binding of linoleic acid to the spike protein blocks virus replication. Thus, unexpectedly, we discovered not only a druggable pocket in the SARS-COV-2 Spike protein, but also a potential drug, linoleic acid, in the pocket, which could be used as antiviral to protect us for infection by the virus. We are now entering pre-clinical trials testing Linoleic acid as an antiviral against SARS-CoV-2. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2020 
Provided To Others? Yes  
Impact Similar fatty acid binding pockets are found frequently in other proteins which are implicated in diseases. Blocking such a pocket with a drug, typically a small molecule, can inhibit the function of such proteins and provide a cure. In our study, the small molecule is linoleic acid - it binds to the pocket and distorts the SARS-Cov-2 Spike protein, dialling down the infectivity of the virus. Our data suggests that linoleic acid could be a drug that could be used as a potent antiviral to protect us from infection. In the future, based on our discovery, new drugs could be developed that bind even better to the pocket to suppress viral infectivity entirely and eliminate Covid-19. We have raised the money for pre-clinical tests to further pursue this idea. We envision a Linoleic Acid-nasal spray that could be used early in SARS-CoV-2 infection to block viral respiration in the respiratory tract. We are currently preparing for clinical phases I and II. In parallel, medical doctors in USA have already used Linoleic Acid using a nebulizer with remarkable success. This is possible in the USA in emergency cases (compassionate care), but not in the UK. We therefore have to go through preclinical tests and clinical trial phases to establish Linoleic Acid as an antiviral drug against Covid-19. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3746712 [Symptom Duration Shortened by Early Initiation of Nebulized Isomerized Linoleic Acid (LA) for Outpatient Treatment of COVID-19.] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3733231 [Case Study Using Nebulized Isomerized Linoleic Acid (LA) for Outpatient Treatment of Symptomatic COVID-19.] 
URL https://science.sciencemag.org/content/370/6517/725.full
 
Title 3D models of the cardiac thin filament at high and low Ca2+ 
Description Models of the cardiac thin filament have been deposited in the international Electron microscopy database. EMDB ID-3576 & 3578 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact Through understanding how cardiac thin filaments are regulated we have gained a insight into the normal function of the heart. The atomic models we have generated also allows the mutations that cause heart disease to be located an important first step in drug design. 
URL https://www.ebi.ac.uk/pdbe/emdb/
 
Title Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2 
Description Structural datasets and coordinates generated during the current study have been deposited in the Electron Microscopy Data Bank (EMDB) under accession numbers EMD-12818 (C3 structure) and EMD-12842 (C1 structure) and in the Protein Data Bank (PDB) under accession numbers: 7OD3 (C3 structure) and 7ODL (C1 structure). 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
Impact The article has an altmetric score of 175, has been tweeted >150 times up to now and led to 16 new and views outlets. The structure has been accessed >50 times already. 
URL http://www.emdataresource.org/EMD-12818
 
Title Structures and atomic model of SARS-CoV-2 spike protein in the open and locked/LA-bound conformation 
Description We deposited the cryo-EM structure of the SARS-CoV-2 spike protein in its open and closed/locked conformation in the Electron Microscopy Data Bank (EMDB) under accession numbers EMD-11145 (C3 closed conformation), EMD-11144 (C1 closed conformation), and EMD-11146 (open conformation) and in the Protein Data Bank (PDB) under accession numbers: 6ZB5 (C3 closed conformation) and 6ZB4 (C1 closed conformation). 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact The structure and model have been downloaded more than 100 times already. We have used the atomic model to search for other potential antivirals that could bind to the free fatty acid binding pocket in the spike protein and block the spike protein in a non-infectious conformation. We have published our results in Die Angewandte 2021. The altrimetric score of our Science paper describing the structure is 1574 which puts it in the top 5% of all research outputs scored by Altmetric. 
URL https://science.sciencemag.org/content/370/6517/725.full
 
Description Becoming a Turing Fellow 
Organisation Alan Turing Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution I became a Turing Fellow in 2019, with this Fellowship I applied for project funding detailed above. This funding has allowed me to hire a research software engineer to create software for the image analysis of cardiac proteins. We participate in regular national meetings with researchers as part of this data science network
Collaborator Contribution The Fellowship and being part of the Turing community has brought me into an extended network of national and international data scientists. The funding opportunity has facilitated the hiring of staff and research outputs. Through an international data study group, scientists connected to this network have worked on a project directly related to my core research, understanding the molecular basis of heart disease.
Impact The technical report from the Data Study Group has been published. https://www.turing.ac.uk/research/publications/data-study-group-final-report-bristol-university-applying-ai-and-machine This is a truly multi-disciplinary collaboration with scientists from every background whose research involves data science. Typically my work in biomedical research benefits from the input of computer scientists and staticians.
Start Year 2019
 
Description Collaboration on agonist bound GPCR structure (drug development) 
Organisation Diamond Light Source
Country United Kingdom 
Sector Private 
PI Contribution We established sample production and drug binding
Collaborator Contribution We collaborate with the membrane protein laboratory, the Rosalind Franklin Institute and eBIC to solve the structure of an agonist bound G-protein coupled receptor (GPCR). We have optimized detergents, tested detergent-alternatives and started lipid cubic phase crystallisation, generation of novel nanobodies binding the GPCR and feezing grids for Cryo-EM in collaboration with the scientists at the Diamond light source.
Impact BBSRC BrisEngBio Proof of Concept award. Megabody in vitro selection and engineering for cryo-EM structure analysis of FFAR1-bound lung fibrosis drugs to treat long COVID,
Start Year 2022
 
Description Collaboration with Prof Adrian Mulholland and Dr Deborah Shoemark for molecular dynamics simulations of SARS-CoV-2 spike protein 
Organisation University of Bristol
Country United Kingdom 
Sector Academic/University 
PI Contribution We have solved the cryo-EM structure of the SARS-CoV-2 spike protein and discovered a free fatty acid binding pocket. We immediately made our atomic model available to Adrian Mulholland and Deborah Shoemark for molecular dynamics simulations
Collaborator Contribution Adrian Mulholland and Deborah Shoemark performed molecular dynamics simulations to understand Linoleic acid binding to the spike protein. Furthermore, they performed molecular modelling to see if they could identify other ligands (other fatty acids ) binding to the hydrophobic pocket in spike protein.
Impact The molecular dynamics simulations were published in Science in September 2020, together with the cryo-EM structure. The molecular modelling study was published in Die Angewandte in 2021.
Start Year 2021
 
Description Collaboration with Prof Burak Kabasakal and FEI Eindhoven (Thermo Fisher) on FtsH cryoEM 
Organisation Ankara University
Country Turkey 
Sector Academic/University 
PI Contribution We have purified FtsH-HflKC complexes for cryo-EM data collection. For image processing we will provide access to the BlueCryo high performance computing cluster in Bristol.
Collaborator Contribution Cryo-EM data (tilted and untilted) were collected at FEI in Eindhoven, the Netherlands. The data will be processed by Dr Burak Kabasakal and his team.
Impact We have collected an additional data set for the FtsH-HflKC sample. Burak Kabasakal will be one of the first group leaders in Turkey using cryo-electron microscopy. He is regarded as one of the pioneers of cryo-EM in Turkey, and supported by FEI. He has given a number of presentations in Turkey about his cryo-EM work since he moved from Bristol to Ankara.
Start Year 2020
 
Description Collaboration with Prof Imre Berger on expression technologies, membrane protein complexes and cryoEM 
Organisation University of Bristol
Country United Kingdom 
Sector Academic/University 
PI Contribution The Berger and Schaffitzel laboratory share data, information, expertise, training of staff, methods and equipment. In the FtsH project the Schaffitzel laboratory generates the plasmids for membrane protein expression and purifies the complexes. Purified protein complexes (from both labs) are used for electron microscopy and image processing and for biophysical, biochemical characterisation.
Collaborator Contribution The Berger laboratory provides training and expertise in state-of-the-art cloning and expression technology: e.g. Gibson assembly, CreLox recombineering and ACEMBL system. In collaboration with the Berger Lab we adapted the MultiBac system for multiprotein expression in insect cells for production of bacterial protein assemblies such as the holo-translocon complex. The ACEMBL system for expression in Escherichia coli has been published in Nat Methods (doi: 10.1038/nmeth.1326) and is patented (CA2754161A1) by Berger.
Impact This collaboration is multidisciplinary, involving advanced molecular biology, biochemistry, biophysics and structural biology. The collaboration with the Berger laboratory resulted in more than 27 publications to date; ten related to expression technologies or membrane protein complexes: (1) Multiprotein Complex Production in E. coli: The SecYEG-SecDFYajC-YidC Holotranslocon doi: 10.1007/978-1-4939-6887-9_18.; (2) A central cavity within the holo-translocon suggests a mechanism for membrane protein insertion. doi: 10.1038/srep38399. (3) Membrane protein insertion and assembly by the bacterial holo-translocon SecYEG-SecDF-YajC-YidC. doi: 10.1042/BCJ20160545. (4) ACEMBL Tool-Kits for High-Throughput Multigene Delivery and Expression in Prokaryotic and Eukaryotic Hosts. doi: 10.1007/978-3-319-27216-0_3. (5) ACEMBLing a multiprotein transmembrane complex: the functional SecYEG-SecDF-YajC-YidC Holotranslocon protein secretase/insertase. doi: 10.1016/bs.mie.2014.12.027. (6) Membrane protein insertion and proton-motive-force-dependent secretion through the bacterial holo-translocon SecYEG-SecDF-YajC-YidC. doi: 10.1073/pnas.1315901111. (7) Robots, pipelines, polyproteins: enabling multiprotein expression in prokaryotic and eukaryotic cells. doi: 10.1016/j.jsb.2011.03.007. (8) Automated unrestricted multigene recombineering for multiprotein complex production. doi: 10.1038/nmeth.1326. (9) Multiprotein expression strategy for structural biology of eukaryotic complexes. PMID: 17355863. (10) Protein complex expression by using multigene baculoviral vectors. PMID: 17117155. This collaborative work has been presented at many conferences, meetings and seminars, highlights are listed above. Moreover, together with Imre Berger, we successfully applied for funding of a state-of-the-art cryo microscope (funded by two Wellcome Trust Multi-User Equipment grants) and the BlueCryo Image Processing Cluster (BBSRC funded). This new equipment is shared in a GW4 facility and helps many researchers in the South West of UK and in Wales to advance their research.
 
Title Methods and material compositions for pan-coronavirus antivirals (Patent number PCT/EP2021/066723) 
Description We discovered a druggable pocket in the SARS-CoV-2 spike protein. Similar pockets are found frequently in other proteins which are implicated in diseases. Blocking such a pocket with a drug, typically a small molecule, can inhibit the function of such proteins and provide a cure. In our study, the small molecule is linoleic acid - it binds to the pocket and distorts the Spike protein, dialling down the infectivity of the virus. Our data suggests that linoleic acid could be already a drug that could be used as a potent antiviral to protect us from SARS-CoV-2 infection. 
IP Reference not available yet 
Protection Patent application published
Year Protection Granted 2021
Licensed Commercial In Confidence
Impact We have been contacted by leading experts from academia and pharma with concrete suggestions how to translate our finding into a treatment against Covid-19. With these experts we have now put together a realistic and fully costed clinical trial plan to translate our discovery to the bedside as soon as possible. We have secured the funding required for pre-clinical tests and work to raise the funding for clinical trial phase 1 and 2.
 
Title Using Linoleic Acid (LA) for Treatment of COVID-19. 
Description Inspired by our Science paper, two medical doctors in USA have used Linoleic Acid already as an antiviral drug against Covid-19. This is possible in emergencies (compassionate care) in USA, but not in UK. We require pre-clinical tests (currently done) and clinical trials (hopefully starting in 3 months in Bristol). https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3746712 [Symptom Duration Shortened by Early Initiation of Nebulized Isomerized Linoleic Acid (LA) for Outpatient Treatment of COVID-19.] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3733231 [Case Study Using Nebulized Isomerized Linoleic Acid (LA) for Outpatient Treatment of Symptomatic COVID-19.] 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2021
Development Status Closed
Impact not applicable yet 
URL https://science.sciencemag.org/content/370/6517/725
 
Title PROOF:A software tool for the automatic identification of PROteins On Filaments 
Description This software tool is used to automatically identify filamentous proteins in noisy Cryo EM images. It uses machine learning and segmentation techniques to identify these medically relevant proteins. The users can then take the output of this software as the input for high resolution structure determination using established image processing packages. 
Type Of Technology Webtool/Application 
Year Produced 2020 
Open Source License? Yes  
Impact The automation of filamentous protein identification will relieve the bottle neck in the existing protocols meaning the time from experiment to output will be significantly reduced. 
URL https://github.com/lohedges/proof-webui
 
Company Name HALO THERAPEUTICS LTD 
Description Halo develops antiviral drugs targeting the SARS-CoV-2 Spike protein linoleic acid binding pocket. 
Year Established 2020 
Impact Funding has been raised from private investors for preclinical studies.
Website https://halo-therapeutics.com/
 
Description 7th annual CCP-EM Spring Symposium, Nottingham, UK 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 presentation of our discovery of a druggable pocket in the SARS-CoV-2 spike protein
Year(s) Of Engagement Activity 2022
 
Description 9th International Singapore Lipidomics Symposium , speaker C Berger-Schaffitzel, 03.03.2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact C. Berger-Schaffitzel presented the discovery of a fatty acid binding pocket in the cryoEM structure of SARS-CoV-2 spike protein to the audience (researchers).
Year(s) Of Engagement Activity 2021
URL https://sling.sg/news-events/isls/
 
Description AFMB, University Aix-Marseille, France, Seminar Speaker (22.06.2020) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact C Berger-Schaffitzel was invited to present my laboratory's current research activity and inform about our cryo-EM research infrastructure.
Year(s) Of Engagement Activity 2020
 
Description BBC Points West and Breakfast news, C Berger-Schaffitzel, 27.01.2021 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact C Berger-Schaffitzel was interviewed about her recent discovery of a free fatty acid binding pocket in the cryoEM structure of SARS-CoV-2 spike protein.
Year(s) Of Engagement Activity 2021
 
Description Biochemical Society Focus webinar: Digital Biology, speaker: C Berger-Schaffitzel (20.11.2020) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact C Berger-Schaffitzel presented the discovery of a free fatty acid binding pocket in the cryoEM structure of SARS-CoV-2 spike protein to the audience (Biochemists).
Year(s) Of Engagement Activity 2020
URL https://biochemistry.org/past-webinars/
 
Description Biochemical Society Meeting "New Approaches for Investigating Nascent Peptide Folding", Downing College, Cambridge, invited speaker and session chair 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact C Berger-Schaffitzel was invited to present our research at the Biochemical Society Meeting at Downing College in Cambridge "New Approaches for Investigating Nascent Peptide Folding" , 11-13. December 2017. The audience was primarily academic, i.e. postgraduate students. The scientific discussions were excellent and new collaborations were discussed.
Year(s) Of Engagement Activity 2017
URL https://www.biochemistry.org/Events/tabid/379/MeetingNo/SA193/view/Conference/Default.aspx
 
Description BrisSynBio Annual Conference, Bristol, speaker Chr. Berger-Schaffitzel, 15.-16.4.2019 
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 Christiane Berger-Schaffitzel presented ongoing cryo-EM projects to the audience (PIs, postdocs, PhD students, undergrads).
Year(s) Of Engagement Activity 2019
URL http://www.bristol.ac.uk/brissynbio/events/2019/annual-conference-2019.html
 
Description Bristol Post, Coolest Person in Bristol 2020, C Berger-Schafftzel 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact C Berger-Schaffitzel was named by Bristol Post the 'coolest person in Bristol' for her Covid-19 related research. including the discovery of a free fatty acid binding pocket in the cryo EM structure of SARS-CoV-2 spike protein.
Year(s) Of Engagement Activity 2020
URL https://www.bristolpost.co.uk/news/bristol-news/bristol-cool-list-2020-citys-4588007
 
Description CCP-EM / CCP-BioSim Workshop - Computation for Biomolecular Cryo-Electron Microscopy and Tomography - Astbury Centre, University of Leeds , Dr Remy Martin (14.7.2017) 
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 Remy Martin (Berger-Schaffitzel group, University of Bristol) presented an integrated approach to the structure and dynamics of the bacterial holo-translocon
Year(s) Of Engagement Activity 2017
URL https://www.ccpem.ac.uk/training/leeds_em_md_2017/ccpem_ccpbiosim_schedule_2017.pdf
 
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 Departmental Seminar, Institute of Biochemistry, Univ. of Zürich, Switzerland 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Presentation of our discovery of a druggable pocket in the cryo-EM structure of SARS-CoV-2 spike protein
Year(s) Of Engagement Activity 2021
 
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 C Berger-Schaffitzel presented the team's 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 C Berger-Schaffitzel 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 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact presentation of our discovery of a druggable pocket in the cryo-EM structure of the SARS-CoV-2 spike protein
Year(s) Of Engagement Activity 2022
URL https://meetings.embo.org/event/22-biomacromolecules
 
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 C Berger-Schaffitzel presented the team's 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 FUTURES2020 public festival funded by the European Commission, speaker C Berger-Schaffitzel (28.11.2020) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact C Berger-Schaffitzel presented the discovery of a free fatty acid binding pocket in the Cryo-EM structure of SARS-CoV-2 spike protein to the audience (general public).
Year(s) Of Engagement Activity 2020
URL https://futures2020.co.uk/events/
 
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. C Berger-Schaffitzel presented the recent cryo-EM structure of the human 48S initiation complex and the holotranslocon project.
She represented the GW4 Facility for High-Resolution cryo-EM and advertised our cryo-EM and image processing infrastructure. CBS sparked interest in this research area and the techniques, 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 Graduate LMB-SciLifeLab Bioscience Symposium, MRC-LMB Cambridge, speaker Chr. Berger-Schaffitzel, 15.09.2017 
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 Chr. Berger-Schaffitzel presented ongoing projects in her laboratory in Bristol to the PhD students, PIs and postdocs.
Year(s) Of Engagement Activity 2017
URL https://www.scilifelab.se/event/graduate-biosciences-symposium/
 
Description International day of women and girls in science 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact Dr Sara Alvira (Postdoc on BB/S008349/1) participated in a workshop on 18th February - an online seminar for 15year old students at a Spanish high school.
This was about antimicrobial resistance and it was to celebrate the 11th february- international day of women and girls in science.

See also https://11defebrero.org/
Year(s) Of Engagement Activity 2020
URL https://www.diariodelemos.es/videoconferencia-en-el-ies-a-pinguela-desde-la-universidad-de-bristol
 
Description Interview Bristol Magazine, 02/2021, C Berger-Schaffitzel 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact C Berger-Schaffitzel was interviewed about her Covid-19 releated research, in particular the discover of a free fatty acid binding pocket in the SARS-CoV-2 spike protein.
Year(s) Of Engagement Activity 2021
URL https://thebristolmag.co.uk/the-pride-of-bristol-dr-christiane-berger-schaffitzel-university-of-bris...
 
Description London RNA Club, invited webinar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Presentation of our recent work related to structures of nonsense-mediated mRNA decay complexes
Year(s) Of Engagement Activity 2021
 
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 Offer Holder Visit Day presentation, University of Bristol 
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 Public/other audiences
Results and Impact ca 60 pupils and parents attended for an Offer Holder Visit Day - my presentation of our recent discovery of a druggable pocket in SARS-CoV-2 spike protein
Year(s) Of Engagement Activity 2022
 
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 SW Structural Biology/CCPEM Relion 3.1 Image Processing Workshop, University of Bristol (25th June 2020) 
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 C Berger-Schaffitzel organised a Relion image processing workshop for early stage career researchers in collaboration with CCPEM and GW4 to train new users of cryo-EM and image processing , i.e. to help familiarise PhD students and postdocs with the new technique and software packages. We meet with this workshop the increased demand of hands-on training in this technology. The workshop will further provide networking opportunities enabling new/ outside users to access the equipment, and bring together scientists with diverse background sparking interesting discussions and increased interest in cryo-EM usage.
Year(s) Of Engagement Activity 2020
 
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 C Berger-Schaffitzel 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 Presentation, Japanese Society for Microscopy 'Frontiers in cellular, viral and molecular microscopy' meeting, University of Bristol, (16.09.2019) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact About 65 researchers attended the presentation, which sparked interest in our research and a vivid discussion afterwards. I received several emails asking for technical advice and collaboration.
Year(s) Of Engagement Activity 2019
URL https://www.yamauchilab.com/post/2019/09/17/two-days-of-great-science-ends-in-success
 
Description Research Complex at Harwell (RCaH), invited seminar, 09.11.2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Christiane Berger-Schaffitzel presented ongoing cryoEM projects to the audience (researchers, PIs, PhD students).
Year(s) Of Engagement Activity 2017
 
Description Research without Borders Exhibition 
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 A PhD student (Tia Salter; SWBio DTP) will take part in the Research without Borders Exhibition this year.
Year(s) Of Engagement Activity 2020
URL https://www.bristol.ac.uk/doctoral-college/current-research-students/events-and-opportunities/resear...
 
Description STEMming Girls: Inspiring New Women Generations in STEM (led by postdoc Dr Sara Alvira de Celis) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact see URL below and also here: http://www.bristol.ac.uk/biochemistry/public/news/2018/international-day-of-women-and-girls-in-science.html
Year(s) Of Engagement Activity 2018
URL https://sruk.org.uk/events/stemming-girls-inspiring-new-women-generations-in-stem/
 
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 C Berger-Schaffitzel 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. She thus raised awareness of the new facilities and increased the interest in applying electron cryo-microscopy to address biological questions. In addition, she presented the 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 Thermo Fischer Webinar. Speaker C Berger-Schaffitzel (03.12.2020) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact C Berger-Schaffitzel presented the discovery of a free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein to the audience (structural biologists).
Year(s) Of Engagement Activity 2020
URL https://www.thermofisher.com/uk/en/home/global/forms/industrial/single-particle-analysis-webinars.ht...
 
Description Turing Institute Blog 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The blog piece gave insight on how the international data study group worked. The article was circulated throughout the Turing Network and will have had national reach, the intention was to promote the initiative. I have had a number of enquiries as a result of this article.
Year(s) Of Engagement Activity 2020
URL https://www.turing.ac.uk/blog/challenge-owners-perspective-inaugural-turing-network-data-study-group
 
Description UCL London, UK, 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 C Berger-Schaffitzel presented our research at the Institute of Molecular and Structural Biology, UCL (24.05.2017). It sparked excellent scientific discussions and led to an invitation to present our research at the Biochemical Society Meeting December 2017.
Year(s) Of Engagement Activity 2017
 
Description UK EM Validation Network online Symposium, 'Cryo-EM Validation in the Age of SARS-CoV-2: Methods, Tools and Applications'. C Berger-Schaffizel (18.11.2020) 
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 Chr. Berger-Schaffitzel presented the recent discovery of a free fatty acid binding pocket in the CryoEM structure of SARS-CoV-2 spike protein to the audience (structural biologists).
Year(s) Of Engagement Activity 2020
URL https://www.emdataresource.org/news/2020_Nov_validation_symposium.html
 
Description UKRI Festival of Tomorrow, workshop , C Berger-Schaffitzel, 25.02.2021 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact C Berger-Schaffitzel presented ongoing research and the use of electron microscopy and image processing to the pupils and teachers (ca 350 participants, online).
Year(s) Of Engagement Activity 2021
URL https://www.ukri.org/news/showcasing-incredible-discoveries-at-swindon-festival-of-tomorrow/
 
Description University of Glasgow, UK, 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 C Berger-Schaffitzel presented the holo-translocon project at the Institute of Molecular, Cell and Systems Biology, University of Glasgow (15.02.2017). It sparked excellent scientific discussions and led to an invitation to present our research at the Biochemical Society Meeting December 2017.
Year(s) Of Engagement Activity 2017
 
Description interview, National Geographic 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interview about our research activity
Year(s) Of Engagement Activity 2022
URL https://www.nationalgeographic.co.uk/science-and-technology/2022/05/this-man-gets-bitten-by-deadly-s...
 
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
 
Description presentation, Wellcome Trust Researcher Meeting, Molecular Mechanisms of Health and Disease, Warwick (29.01.2020) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact About 80 researchers attended the meeting organised by the Wellcome Trust. My presenation sparked questions and discussion, and it resulted in emails asking for further details and interest in collaboration.
Year(s) Of Engagement Activity 2020