BrisSynBio: Bristol Centre for Synthetic Biology
Lead Research Organisation:
University of Bristol
Department Name: Chemistry
Abstract
Synthetic biology is a new scientific discipline that aims to make the engineering of biological systems easier, more predictable and more reliable. Synthetic biologists aim to develop new techniques, technologies and reagents that will allow biological or biologically based products to be made easily, quickly and cheaply, and in sufficient quantities to make them useful. Advances in this area have the potential to provide us with new fuels, materials, diagnostics and medicines, and offer solutions to many of the major global challenges that we face today. For example providing sufficient food for the world's population and reducing our dependence on fossil fuels.
For synthetic biology to meet these challenges, however, will require the concerted efforts of large groups of scientists working together in teams combining their expertise, skills and knowledge. To achieve this we aim to establish BrisSynBio (BSB), a Bristol-based Synthetic Biology Research Centre, which will bring together a group of scientists from a range of different research backgrounds, e.g. biology, chemistry, computer science, engineering and robotics, mathematics and physics.
BSB researchers will combine their expertise in such a way that global challenges can be met and resolved. Examples of the type of work that BSB scientists will carry out include: modifying biosynthetic pathways in microorganisms such to produce new antibiotics; assembling virus-like particles to present new routes to vaccines; building simple cells from scratch for use in the production of important but sometimes toxic chemicals; using red blood cells to deliver complex molecules like anti-cancer drugs directly to tumours; and reprograming bacteria to perform useful tasks like sensing environmental pollutants.
Within the BSB, researchers will be organised into teams with complementary skills who will work together on these challenging projects. There will be lots of communication between the teams, and new and exciting research will emerge as a result. Teams will be linked together by cross-cutting themes to promote interdisciplinarity and exchange of ideas. To help foster and develop interactions further, BSB academics will attend monthly discussion meetings, and all BSB academics and researchers will attend monthly research seminars and an annual 2-day regional symposium.
The University of Bristol has recently invested heavily in new buildings and laboratory space, perfect for housing BSB. Now we need further investment to purchase the essential equipment that we will need to underpin and progress our research, and also to attract more scientists to expand synthetic-biology activities. We will also work in collaboration with a range of different project partners including researchers form around the world, the public and policy makers, and industrialists, such that we can maximise the impact of BrisSynBio.
Finally, synthetic biology is not without controversy, the notion of tinkering with biology and life does not sit comfortably with everyone. Therefore, it is very important that all BrisSynBio members are trained to consider the ethical, legal and social implications of their work, placing it in a broader societal context. To achieve this BSB members will be trained in responsible innovation and public engagement, and encouraged to put these new skills into practice through commercialising their work where appropriate, and at 6-monthly science cafes and public dialogues.
For synthetic biology to meet these challenges, however, will require the concerted efforts of large groups of scientists working together in teams combining their expertise, skills and knowledge. To achieve this we aim to establish BrisSynBio (BSB), a Bristol-based Synthetic Biology Research Centre, which will bring together a group of scientists from a range of different research backgrounds, e.g. biology, chemistry, computer science, engineering and robotics, mathematics and physics.
BSB researchers will combine their expertise in such a way that global challenges can be met and resolved. Examples of the type of work that BSB scientists will carry out include: modifying biosynthetic pathways in microorganisms such to produce new antibiotics; assembling virus-like particles to present new routes to vaccines; building simple cells from scratch for use in the production of important but sometimes toxic chemicals; using red blood cells to deliver complex molecules like anti-cancer drugs directly to tumours; and reprograming bacteria to perform useful tasks like sensing environmental pollutants.
Within the BSB, researchers will be organised into teams with complementary skills who will work together on these challenging projects. There will be lots of communication between the teams, and new and exciting research will emerge as a result. Teams will be linked together by cross-cutting themes to promote interdisciplinarity and exchange of ideas. To help foster and develop interactions further, BSB academics will attend monthly discussion meetings, and all BSB academics and researchers will attend monthly research seminars and an annual 2-day regional symposium.
The University of Bristol has recently invested heavily in new buildings and laboratory space, perfect for housing BSB. Now we need further investment to purchase the essential equipment that we will need to underpin and progress our research, and also to attract more scientists to expand synthetic-biology activities. We will also work in collaboration with a range of different project partners including researchers form around the world, the public and policy makers, and industrialists, such that we can maximise the impact of BrisSynBio.
Finally, synthetic biology is not without controversy, the notion of tinkering with biology and life does not sit comfortably with everyone. Therefore, it is very important that all BrisSynBio members are trained to consider the ethical, legal and social implications of their work, placing it in a broader societal context. To achieve this BSB members will be trained in responsible innovation and public engagement, and encouraged to put these new skills into practice through commercialising their work where appropriate, and at 6-monthly science cafes and public dialogues.
Technical Summary
The overarching goal of BrisSynBio will be to provide an intellectual and technical framework for innovative and collaborative research, facilitated by cutting-edge instrumentation. The focus will be on world-class fundamental science leading to transformative solutions to meet global challenges in healthcare, food security, and industrial biotechnology.
BSB comprises 21 Core and >20 Associate Members, organised in 3 Research Strands and 3 Cross-cutting Themes that reflect Bristol strengths, and the potential for growth in synthetic biology both locally and nationally. Across these, initial BSB activity will progress 9 multidisciplinary synergy projects. The Associate Membership will be expanded to broaden BSB's research base for future diversification and development of new projects. BSB support staff and fellows would be co-located in the new University of Bristol Life Sciences Building.
Over 5 years, BSB will support ~15 synthetic-biology synergy projects. Those outlined here account for ~2/3 of the funds requested, leaving ~1/3 for new projects. To ensure delivery on these and to enable future programmes, BSB research will be underpinned by existing and requested major facilities, e.g.: high-throughput liquid-handling robotics, NMR spectroscopy, and peptide synthesis; and high-performance computing. For added value and best practice, the new equipment would be co-located with existing equipment in Research Suites across 3 Faculties.
To build the synthetic-biology community, locally and regionally, BSB will establish research meetings, seminars and an annual symposium. BSB outreach activities would include: public engagement; training for research staff in public engagement and responsible innovation; and fostering links with local and national industry and SMEs. BSB would work closely with our partner South West universities; the Imperial-led IKC in Synthetic Biology; the Bristol-Oxford-Warwick CDT; and other Synthetic Biology Research Centres
BSB comprises 21 Core and >20 Associate Members, organised in 3 Research Strands and 3 Cross-cutting Themes that reflect Bristol strengths, and the potential for growth in synthetic biology both locally and nationally. Across these, initial BSB activity will progress 9 multidisciplinary synergy projects. The Associate Membership will be expanded to broaden BSB's research base for future diversification and development of new projects. BSB support staff and fellows would be co-located in the new University of Bristol Life Sciences Building.
Over 5 years, BSB will support ~15 synthetic-biology synergy projects. Those outlined here account for ~2/3 of the funds requested, leaving ~1/3 for new projects. To ensure delivery on these and to enable future programmes, BSB research will be underpinned by existing and requested major facilities, e.g.: high-throughput liquid-handling robotics, NMR spectroscopy, and peptide synthesis; and high-performance computing. For added value and best practice, the new equipment would be co-located with existing equipment in Research Suites across 3 Faculties.
To build the synthetic-biology community, locally and regionally, BSB will establish research meetings, seminars and an annual symposium. BSB outreach activities would include: public engagement; training for research staff in public engagement and responsible innovation; and fostering links with local and national industry and SMEs. BSB would work closely with our partner South West universities; the Imperial-led IKC in Synthetic Biology; the Bristol-Oxford-Warwick CDT; and other Synthetic Biology Research Centres
Planned Impact
1. TRAINING
BrisSynBio will recruit the most-promising early career researchers to its PDRA and Fellowship positions. Through its multidisciplinary projects, seminar programmes, outreach activities and courses, BSB will train them thoroughly in all aspects of synthetic biology. In addition, we will establish workshops and summer schools in allied synthetic-biology methods to provide training nationally. In this way, BSB will respond directly to the Roadmap recommendation "to build a skilled, energised synthetic biology community".
2. EXCHANGE OF SKILLS AND NEW WAYS OF WORKING
Synthetic biology is a multidisciplinary subject, combing the life and physical sciences with engineering and modelling to improve design and engineering of biological systems. BSB will provide an exemplar to promote this new way of working. Its structure-with Research Strands, Themes and meetings-will facilitate this, allowing researchers to exchange ideas freely, and to develop new materials and methods together quickly to tackle ambitious and challenging research problems. Specifically, all projects will be undertaken by teams involving: multiple PIs and PDRAs working towards a common goal; both physical and life scientists; input from mathematical and/or molecular modelling; and be overseen by engineering "mentors".
3. EXPLOITATION
The above vision will naturally lead to projects diversifying in directions not envisaged from the outset. This will be managed by PIs and researchers to avoid projects becoming diffuse. This approach also brings with it new opportunities, for example leading to IP and consequently possibilities for licensing, spin outs, and entrepreneurship. Whilst we do not anticipate all projects leading to commercialisation, those that do will be supported fully through the Research and Enterprise Division, the Severnside Alliance for Translational Research, the Elizabeth Blackwell Institute for Health, and links that we will foster with industry and SMEs. We will also use BSB as a mechanism to develop a synthetic-biology industrial hub to spark translation in a region that has a relatively low number of start-up and SMEs.
4. OUTREACH TO OTHER SYNTHETIC-BIOLOGY SCIENTISTS AND CENTRES
We envisage that the above will also benefit researchers and academics outside the BSB developing synthetic-biology programmes; similarly, we are keen to learn best practice from others. In addition to attendance at academic conferences nationally and overseas, BSB will use the following to reach out to other academics and industrialists to exchange these ideas:
(i) The PI, Woolfson, and Co-Is are already linked in to other UK synthetic-biology researchers through conferences and the previously funded Synthetic Biology Networks (Woolfson headed one of these). We will use these as a basis for cementing old links and fostering new ones.
(ii) Bristol is a partner in the recently funded, Imperial-led IKC in Synthetic Biology (SynbiCITE). This will be particularly useful for seeking out and developing industrial and SME partners for exploiting and translating BSB research findings.
(iii) Bristol is an equal partner with Oxford and Warwick in a CDT (Centre for Doctoral Training) bid submitted to EPSRC. If funded, this will facilitate links between academics, the exchange of ideas and people, and the development of joint projects with the two other institutes.
(iv) Finally, the BSB Annual Symposium will provide a hub for activity in synthetic biology in the South West.
5. GENERAL OUTREACH AND PUBLIC ENGAGEMENT
Through the Synthetic Components Network and the Centre for Public Engagement, Bristol has been exemplary in public engagement in synthetic biology: it has hosted or contributed to science cafes, public lectures, live webcasts, the Public Dialogue, and the training of early career scientists in this area. It will build these activities through 6-monthly public dialogue events, with partners such as Explore@Bristol and ThinkTank.
BrisSynBio will recruit the most-promising early career researchers to its PDRA and Fellowship positions. Through its multidisciplinary projects, seminar programmes, outreach activities and courses, BSB will train them thoroughly in all aspects of synthetic biology. In addition, we will establish workshops and summer schools in allied synthetic-biology methods to provide training nationally. In this way, BSB will respond directly to the Roadmap recommendation "to build a skilled, energised synthetic biology community".
2. EXCHANGE OF SKILLS AND NEW WAYS OF WORKING
Synthetic biology is a multidisciplinary subject, combing the life and physical sciences with engineering and modelling to improve design and engineering of biological systems. BSB will provide an exemplar to promote this new way of working. Its structure-with Research Strands, Themes and meetings-will facilitate this, allowing researchers to exchange ideas freely, and to develop new materials and methods together quickly to tackle ambitious and challenging research problems. Specifically, all projects will be undertaken by teams involving: multiple PIs and PDRAs working towards a common goal; both physical and life scientists; input from mathematical and/or molecular modelling; and be overseen by engineering "mentors".
3. EXPLOITATION
The above vision will naturally lead to projects diversifying in directions not envisaged from the outset. This will be managed by PIs and researchers to avoid projects becoming diffuse. This approach also brings with it new opportunities, for example leading to IP and consequently possibilities for licensing, spin outs, and entrepreneurship. Whilst we do not anticipate all projects leading to commercialisation, those that do will be supported fully through the Research and Enterprise Division, the Severnside Alliance for Translational Research, the Elizabeth Blackwell Institute for Health, and links that we will foster with industry and SMEs. We will also use BSB as a mechanism to develop a synthetic-biology industrial hub to spark translation in a region that has a relatively low number of start-up and SMEs.
4. OUTREACH TO OTHER SYNTHETIC-BIOLOGY SCIENTISTS AND CENTRES
We envisage that the above will also benefit researchers and academics outside the BSB developing synthetic-biology programmes; similarly, we are keen to learn best practice from others. In addition to attendance at academic conferences nationally and overseas, BSB will use the following to reach out to other academics and industrialists to exchange these ideas:
(i) The PI, Woolfson, and Co-Is are already linked in to other UK synthetic-biology researchers through conferences and the previously funded Synthetic Biology Networks (Woolfson headed one of these). We will use these as a basis for cementing old links and fostering new ones.
(ii) Bristol is a partner in the recently funded, Imperial-led IKC in Synthetic Biology (SynbiCITE). This will be particularly useful for seeking out and developing industrial and SME partners for exploiting and translating BSB research findings.
(iii) Bristol is an equal partner with Oxford and Warwick in a CDT (Centre for Doctoral Training) bid submitted to EPSRC. If funded, this will facilitate links between academics, the exchange of ideas and people, and the development of joint projects with the two other institutes.
(iv) Finally, the BSB Annual Symposium will provide a hub for activity in synthetic biology in the South West.
5. GENERAL OUTREACH AND PUBLIC ENGAGEMENT
Through the Synthetic Components Network and the Centre for Public Engagement, Bristol has been exemplary in public engagement in synthetic biology: it has hosted or contributed to science cafes, public lectures, live webcasts, the Public Dialogue, and the training of early career scientists in this area. It will build these activities through 6-monthly public dialogue events, with partners such as Explore@Bristol and ThinkTank.
Organisations
- University of Bristol (Lead Research Organisation, Project Partner)
- EPSRC (Co-funder)
- Max Planck Society (Collaboration)
- Bruker Corporation (Collaboration)
- Newcastle University (Collaboration)
- Oracle Corporation (Collaboration)
- University of Dundee (Collaboration)
- Ubon Ratchathani University (Collaboration)
- Syngenta International AG (Collaboration)
- UNIVERSITY OF BIRMINGHAM (Collaboration)
- UCB Pharma (Collaboration)
- University of Bristol (Collaboration)
- GlaxoSmithKline (GSK) (Collaboration)
- Celltech Group plc (Project Partner)
- Bruker UK Ltd (Project Partner)
- Syngenta (Project Partner)
- GSK (Project Partner)
Publications
Pakamwong B
(2024)
Ligand-Based Virtual Screening for Discovery of Indole Derivatives as Potent DNA Gyrase ATPase Inhibitors Active against Mycobacterium tuberculosis and Hit Validation by Biological Assays
in Journal of Chemical Information and Modeling
Pakamwong B
(2022)
Identification of Potent DNA Gyrase Inhibitors Active against Mycobacterium tuberculosis.
in Journal of chemical information and modeling
Oliveira ASF
(2020)
Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors.
in bioRxiv : the preprint server for biology
Oliveira ASF
(2021)
A potential interaction between the SARS-CoV-2 spike protein and nicotinic acetylcholine receptors.
in Biophysical journal
Oliveira ASF
(2019)
A General Mechanism for Signal Propagation in the Nicotinic Acetylcholine Receptor Family.
in Journal of the American Chemical Society
Oliveira ASF
(2021)
Dynamical nonequilibrium molecular dynamics reveals the structural basis for allostery and signal propagation in biomolecular systems.
in The European physical journal. B
Oliveira ASF
(2023)
SARS-CoV-2 spike variants differ in their allosteric responses to linoleic acid.
in Journal of molecular cell biology
Oliveira ASF
(2019)
Identification of the Initial Steps in Signal Transduction in the a4ß2 Nicotinic Receptor: Insights from Equilibrium and Nonequilibrium Simulations.
in Structure (London, England : 1993)
Oliveira A. S. F.
(2019)
Nicotine-induced conformational changes in the a4ß2 nicotinic receptor
in EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
Oliveira A
(2023)
Fluctuation Relations to Calculate Protein Redox Potentials from Molecular Dynamics Simulations
in Journal of Chemical Theory and Computation
Olenik M
(2023)
Fluctuations of cell geometry and their nonequilibrium thermodynamics in living epithelial tissue.
in Physical review. E
O'Hagan MP
(2020)
Enhanced sampling molecular dynamics simulations correctly predict the diverse activities of a series of stiff-stilbene G-quadruplex DNA ligands.
in Chemical science
O'Hagan MP
(2020)
Visible-light photoswitching of ligand binding mode suggests G-quadruplex DNA as a target for photopharmacology.
in Chemical communications (Cambridge, England)
O'Hagan MP
(2019)
A Photoresponsive Stiff-Stilbene Ligand Fuels the Reversible Unfolding of G-Quadruplex DNA.
in Angewandte Chemie (International ed. in English)
O'Hagan M
(2019)
A Photoresponsive Stiff-Stilbene Ligand Fuels the Reversible Unfolding of G-Quadruplex DNA
in Angewandte Chemie
O'Connor M
(2018)
Sampling molecular conformations and dynamics in a multiuser virtual reality framework.
in Science advances
O'Connor M
(2019)
Interactive molecular dynamics in virtual reality from quantum chemistry to drug binding: An open-source multi-person framework
in The Journal of Chemical Physics
Nutho B
(2019)
The reaction mechanism of Zika virus NS2B/NS3 serine protease inhibition by dipeptidyl aldehyde: a QM/MM study.
in Physical chemistry chemical physics : PCCP
Nutho B
(2019)
QM/MM Study on Cleavage Mechanism Catalyzed by Zika Virus NS2B/NS3 Serine Protease
in Biophysical Journal
Nutho B
(2019)
Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations Support a Concerted Reaction Mechanism for the Zika Virus NS2B/NS3 Serine Protease with Its Substrate.
in The journal of physical chemistry. B
Noy A
(2017)
Interference between Triplex and Protein Binding to Distal Sites on Supercoiled DNA.
in Biophysical journal
Nofiani R
(2018)
Strobilurin biosynthesis in Basidiomycete fungi.
in Nature communications
Nofiani R
(2018)
Strobilurin biosynthesis in Basidiomycete fungi
Niitsu A
(2017)
Membrane-spanning a-helical barrels as tractable protein-design targets.
in Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Newport TD
(2019)
The MemProtMD database: a resource for membrane-embedded protein structures and their lipid interactions.
in Nucleic acids research
Nett N
(2021)
A robust and stereocomplementary panel of ene-reductase variants for gram-scale asymmetric hydrogenation
in Molecular Catalysis
Nesabi A
(2024)
Molecular dynamics simulations as a guide for modulating small molecule aggregation.
in Journal of computer-aided molecular design
Nemoz C
(2018)
XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining.
in Nature structural & molecular biology
Nawrocki W
(2023)
In situ time-resolved spectroelectrochemistry reveals limitations of biohybrid photoelectrode performance
in Joule
Naudin EA
(2022)
From peptides to proteins: coiled-coil tetramers to single-chain 4-helix bundles.
in Chemical science
Nancolas B
(2017)
Saccharomyces cerevisiae Atf1p is an alcohol acetyltransferase and a thioesterase in vitro.
in Yeast (Chichester, England)
Nair AV
(2020)
Structure and mechanism of a dehydratase/decarboxylase enzyme couple involved in polyketide ß-methyl branch incorporation.
in Scientific reports
Naafs B
(2021)
Molecular dynamics simulations support the hypothesis that the brGDGT paleothermometer is based on homeoviscous adaptation
in Geochimica et Cosmochimica Acta
Myers CJ
(2017)
A standard-enabled workflow for synthetic biology.
in Biochemical Society transactions
Musgaard M
(2016)
Steered Molecular Dynamics Simulations Predict Conformational Stability of Glutamate Receptors.
in Journal of chemical information and modeling
Mullally G
(2020)
5' modifications to CRISPR-Cas9 gRNA can change the dynamics and size of R-loops and inhibit DNA cleavage.
in Nucleic acids research
Mulholland AJ
(2020)
COVID19 - Computational Chemists Meet the Moment.
in Journal of chemical information and modeling
Mulholland AJ
(1996)
Simulations of enzymic reactions.
in Biochemical Society transactions
Mulholland AJ
(2016)
Dispelling the effects of a sorceress in enzyme catalysis.
in Proceedings of the National Academy of Sciences of the United States of America
Mulholland AJ
(2023)
Science after Brexit: bright spots on the Horizon?
in EMBO reports
Mulholland A
(1998)
A model of the condensation step in the citrate synthase reaction
in Journal of Molecular Structure: THEOCHEM
| Title | (still) Invincible. A second run |
| Description | BrisSynBio and Kilter Theatre present INVINCIBLE, a future-facing, immersive play exploring the personal and societal conflicts surrounding the emerging science of synthetic biology. Specifically the treatment explores a synthetic biology-based preventative treatment for mental health. Staged in the pressure-cooker environment of a real residential flat, set in 2048, three women traverse three generations as the political and scientific become intensely personal. Each performance will be followed by a discussion with the cast and researchers working in synthetic biology - putting each and every audience member at the heart of a contemporary moral dilemma. |
| Type Of Art | Performance (Music, Dance, Drama, etc) |
| Year Produced | 2018 |
| Impact | A second run of this sell out show was commissioned for 2018 with the objective of engaging new audiences, and in-so-doing leveraging further impact from this thoughtful and thought-provoking project. This has now been attended by total audience of 515, including 98 teachers and secondary school children, policy makers, mental health practitioners, and publics from across generations. This was followed up with a science-café style evening which was attended by ~100 audience members. This has led to the establishment of a 'synbio sounding board'; a group of people who are interested in continued engagement with synthetic biology researchers at the University, and willing to contribute to further discussion and debate on this topic. Kilter have since secured EPSRC Impact Acceleration Account funding to roll this approach out to researchers working in Quantum Technologies and Virtual Reality at Bristol. In September 2018 we will hold a residential RRI workshop for early career researchers exploring implications of synthetic biology through arts practice in collaboration with the EU-funded PERFORM project and ONCE artists collective. |
| URL | https://www.youtube.com/watch?v=71K6h3wg1i8 |
| Title | BrisSynBio illustration |
| Description | Illustrative prepresentation of BrisSynBio by local Bristol illustrator and street artist Andy Council. |
| Type Of Art | Artwork |
| Year Produced | 2014 |
| Impact | None yet. |
| URL | http://www.bristol.ac.uk/brissynbio/ |
| Title | Grace Mullally PIP |
| Description | As part of her PIP, Grace Mullally is working with Claudia Stocker at Vivid Biology, and is organising a collaborative scientist-artist partnership to result in exhibited artworks. |
| Type Of Art | Artistic/Creative Exhibition |
| Year Produced | 2017 |
| Impact | None as yet |
| Title | Invincible immersive theatre |
| Description | BrisSynBio and Kilter Theatre present INVINCIBLE, a future-facing, immersive play exploring the personal and societal conflicts surrounding the emerging science of synthetic biology. Specifically the treatment explores a synthetic biology-based preventative treatment for mental health. Staged in the pressure-cooker environment of a real residential flat, set in 2048, three women traverse three generations as the political and scientific become intensely personal. Each performance will be followed by a discussion with the cast and researchers working in synthetic biology - putting each and every audience member at the heart of a contemporary moral dilemma. |
| Type Of Art | Performance (Music, Dance, Drama, etc) |
| Year Produced | 2017 |
| Impact | Unforeseen opportunity for reflection for the PDRAs involved in the development of the script and in the performances themselves. Feedback includes: "It has allowed me to carefully think about what aspects of synthetic biology are important to me and the worries that I have. These were not always easy to precisely define and this process has allowed me to think about this in a new way -- often from the view point of others outside the scientific community". "One clear thing that came out of the Q&A sessions that I was involved in was a strong sense that using nanoparticle-based therapeutics for physical vs mental health conditions had very different ethical implications for the public (with the majority believing that self-regulating systems should only be used to treat physical conditions)". The performance was offered in 2017 and 2017. In 2017 it was attended by an audience of 344, including 98 teachers and secondary school children. Input from the audiences was collected throughout and discussed with researchers and academics immediately following the performance. |
| URL | https://www.youtube.com/watch?v=71K6h3wg1i8 |
| Title | Living in Frames |
| Description | Musical score co-produced by early career synthetic biologists, and professional composer Verity Standen during a two day residential Responsible Research and Innovation retreat. |
| Type Of Art | Composition/Score |
| Year Produced | 2018 |
| Impact | Reflection for the early career researchers involved |
| Title | SYNTHETIC | An exploration of synthetic biology through Art |
| Description | An exhibition of four synthetic biology-art collaborations. Products include some of the exhibited artworks. Artists involved were: Katy Connor; Imogan Coulter; Claudia Sticker; and Theo Wood. |
| Type Of Art | Artwork |
| Year Produced | 2017 |
| Impact | Reflection for the synthetic biologists involved in the collaborations. Increased awareness of synthetic biology research and potential applications for the audiences. |
| URL | http://www.bris.ac.uk/news/2017/september/synthetic-biology-art-exhibition.html |
| Title | Tate Exchange Residency (Theo Wood) |
| Description | Theme: Movement Topic: gene editing The residency will: - providing a brief overview of CRISPR (A5 flyer to take away) - provide plus further information on encapsulated sheets - some news headlines (not fake), some headlines/cartoons (some fake) from the poster developed for SYNTHETIC (2017) - engage with visitors by playing 'Dilemma' the board game. The game is for 2-6 players aimed at 11+. This will last no more than maximum 15-20mins. - provide opportunity for post-it comments |
| Type Of Art | Artistic/Creative Exhibition |
| Year Produced | 2019 |
| Impact | None yet |
| URL | https://www.tate.org.uk/search?daterange=fromnow&sort=finish_time&type=event&venue=453990 |
| Description | Key findings have been reported via our final report. |
| Exploitation Route | NA |
| Sectors | Agriculture Food and Drink Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | BrisSynBio was one of 6 UKRI-funded Synthetic Biology Research Centres (SBRCs). It was a pan-University endeavour, with training, research, and facilities across 3 Faculties and 6 Schools at the University of Bristol (UoB). BrisSynBio partners were Social Sciences at the University of West England (UWE), and Philosophy at the University of Maastricht. Overall, the BrisSynBio SBRC grant funded 24 research projects, which engaged ~50 academics, and supported 7 technicians, 60 post-doctoral researchers and 33 PhD students. With Oxford (as lead) and Warwick, UoB partners in the EPSRC/BBSRC-funded Synthetic Biology CDT, with 24 PhD students in total coming to Bristol. As well as hosting these students, UoB BrisSynBio academics contributed to the teaching, management, and overall smooth delivery of the CDT. They also taught, supervised, and mentored synthetic-biology PhD students for UKRI (e.g., SWBio DTP and other CDTs), Dstl, Industry and EU programmes. To date, BrisSynBio has published over 700 papers, contributed to 10 patents, and spun out 8 biotech companies. Since its establishment in 2014, BrisSynBio funding and Centre status have also helped secure additional research funding of over £150M. Building on these investments, synthetic biology at the UoB is thriving and growing. The UoB has recognised this excellence by establishing the Bristol BioDesign Institute (BBI), and by co-funding the Max Planck-Bristol Centre for Minimal Biology (MPBC) with the Max Planck Society, Germany. Highlighted outputs are in fields such as: rational and computational protein design (Burgess et al., 2015, J.A.C.S. (1); Burton et al., 2016, Nature Chem. (2)); biotechnology (Byrne et al., 2016, J.A.C.S. (3)); minimal biology (Tang et al., 2015, Chem. Comm. (4)); therapeutics (Trakarnsanga et al., 2017, Nature Comms. (5)); and plant synthetic biology (Winfield et al., 2016 and Allen et al., 2017, Plant Biotech. J. (6, 7)). Most recently BrisSynBio groups have contributed to the COVID-19 research effort (Daly et al., 2020 and Toezler et al., 2020, Science (8, 9)). These research successes and our trained personnel have contributed to the boom in biotech innovation in and around Bristol, which is exemplified by the Science Creates incubators and associated resources. Specifically, BrisSynBio's Innovation Programme has: raised >£7.5M in translational grants and industry funding; filed 10 patents; generated further IP that has underpinned the incorporation of 5 of the synthetic-biology companies; supported the incorporation and growth of another 3 companies; funded 11 industry placements for early career researchers and 2 year-long BioDesign Innovation Fellowships; delivered programmes of entrepreneurial and innovation training; hosted and contributed to industry engagement events relevant to the life sciences and bioeconomy; and contributed to the growth of Bristol and the South West as a new leader in synthetic biology and deep tech innovation. Companies that exist as a direct consequence of BrisSynBio are: Cytoseek, which targets cell therapies to treat solid tumours; CDotBio and Glaia, which are developing nanotechnologies for agriculture; Halo, which develops pan-coronavirus antivirals; Imophoron, which is advancing new vaccine platform technologies; Rosa Biotech, which is combining protein design and AI to develop new in vitro diagnostics; Scarlet Therapeutics, which is adapting red blood cells for cell-based therapies; and Zentraxa, which is designing functional biopolymer materials. On partnerships and internationalism, in addition to the abovementioned MPBC, BrisSynBio and its academics have: led a BBSRC-funded, pan-European consortium in Computational Protein Design (CuPiD); contributed to three EU International Training Networks; maintained an active portfolio of collaborations across South East Asia in the fields of synthetic biology for antimicrobial resistance and vaccine manufacture; and coordinated an EC FET Open award to develop novel snakebite therapeutics. In responsible research and innovation (RRI), BrisSynBio partnered with the EU-funded PERFORM and RRI in Practice projects. In Public Engagement we have: delivered talks and interactive sessions at numerous schools; contributed to Pint of Science, Soapbox Science, Skirting Science; supported stand-up comedy on synthetic-biology at the Edinburgh Fringe Festival (Do Scientists Dream of Synthetic Sheep?); nurtured long-term sci-art collaborations and hosted exhibitions; co-produced an immersive theatre show; and appeared on national radio and television. Finally, the above successes of BrisSynBio have underpinned the establishment of BrisEngBio, the Bristol Centre for Engineering Biology, which had seed funding from UKRI through the National Engineering Biology Programme (NEBP). BrisEngBio's aim was to accelerate the translation of discovery synthetic biology into real-world benefits; and to maintain Bristol as a national and international leader in synthetic and engineering biology. BrisEngBio was multidisciplinary, involving 55 academics across 4 Faculties and 11 Schools at UoB. It bridged the Discovery- and Application-Inspired Themes and Challenges of the NEBP, and fostered the best fundamental synthetic biology and supported its translation to contribute to the UK bioeconomy. |
| First Year Of Impact | 2016 |
| Sector | Aerospace, Defence and Marine,Agriculture, Food and Drink,Chemicals,Digital/Communication/Information Technologies (including Software),Education,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal Economic Policy & public services |
| Description | All Party Parliamentary Group on Artificial Intelligence Community (Hauert) |
| Geographic Reach | National |
| Policy Influence Type | Contribution to a national consultation/review |
| Description | Biodesign for the bioeconomy: UK Synthetic Biology strategic plan 2016 |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Membership of a guideline committee |
| Impact | This strategic plan, published by the Synthetic Biology Leadership Council (SBLC), aims to accelerate the commercialisation of synthetic biology products and services with clear public benefit, building upon the strength of the UK research base. It focuses on five key areas of strategic importance: Accelerating industrialisation and commercialisation Maximising the capability of the innovation pipeline Building an expert workforce Developing a supportive business environment, and Building value from national and international partnerships. |
| URL | https://connect.innovateuk.org/documents/2826135/31405930/BioDesign+for+the+Bioeconomy+2016+-+DIGITA... |
| Description | DSIT Engineering Biology Consultation |
| Geographic Reach | National |
| Policy Influence Type | Contribution to a national consultation/review |
| URL | https://www.gov.uk/government/publications/national-vision-for-engineering-biology/national-vision-f... |
| Description | Evidence about Engineering Biology to the Science and Technology Committee (House of Lords) |
| Geographic Reach | Europe |
| Policy Influence Type | Contribution to a national consultation/review |
| URL | https://publications.parliament.uk/pa/ld5901/ldselect/ldsctech/55/55.pdf |
| Description | Government urges funders to consider scrapping Researchfish |
| Geographic Reach | National |
| Policy Influence Type | Contribution to a national consultation/review |
| URL | https://www.gov.uk/government/publications/review-of-research-bureaucracy |
| Description | Large-Scale Computing Opportunities and Challenges. A Report from a Supercomputing Task Force for BBSRC and MRC |
| Geographic Reach | National |
| Policy Influence Type | Contribution to a national consultation/review |
| URL | https://doi.org/10.5281/zenodo.11079792 |
| Description | Nuffield Council on Bioethics: Genome editing call for evidence (Meacham) |
| Geographic Reach | National |
| Policy Influence Type | Contribution to a national consultation/review |
| Impact | Genome editing techniques such as the CRISPR-Cas9 system are transforming many areas of biological research. The techniques have been embraced with enthusiasm by many researchers but have also provoked debate about possible future uses, including in human germ line modification, ecological engineering, and novel plant breeding. This project is being carried out in stages considering first the impact of genome editing in research and the range of questions to which this gives rise, and then developing practical ethical guidance for specific field(s) of application. |
| URL | http://nuffieldbioethics.org/project/genome-editing/ |
| Description | Nuffield Council on Bioethics: Naturalness report (Meacham) |
| Geographic Reach | National |
| Policy Influence Type | Contribution to a national consultation/review |
| Impact | When people describe something as natural, they might mean it is good, acceptable, safe or healthy. When something is described as unnatural, people can mean it is bad, unacceptable or dangerous. Views about what is natural or unnatural can affect the development and uptake of new technologies. This project examined how ideas about naturalness feature in and affect public discussions about the ethics of science, technology and medicine. The recommendations aim to improve communication and understanding between people with different views about naturalness. |
| URL | http://nuffieldbioethics.org/project/naturalness/ |
| Description | Problems caused by introgessions |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | Wheat breeding companies were made aware about the effect that introgressions have on recombination and why this may lead to difficulties in the future, this has caused some companies to re-examine their breeding strategies |
| Description | Research data and policy |
| Geographic Reach | National |
| Policy Influence Type | Contribution to new or improved professional practice |
| URL | https://www.chemistryworld.com/news/ukri-finds-itself-in-hot-water-too-over-researchfish-cyberbullyi... |
| Description | Royal Society Working Group on Machine Learning (Hauert) |
| Geographic Reach | National |
| Policy Influence Type | Membership of a guideline committee |
| Impact | Not yet evaluated. |
| URL | http://royalsociety.org/topics-policy/projects/machine-learning/ |
| Description | Science after Brexit: bright spots on the Horizon? |
| Geographic Reach | Europe |
| Policy Influence Type | Contribution to a national consultation/review |
| URL | https://digital-strategy.ec.europa.eu/en/news/united-kingdom-joins-horizon-europe-programme#:~:text=... |
| Description | UK Robotics and Autonomous Systems Sector Deal Committee (Hauert) |
| Geographic Reach | National |
| Policy Influence Type | Membership of a guideline committee |
| Impact | Established to help understand UK-wide activity to inform RAS sector deal negotiations. Impact not yet evaluated. |
| URL | https://www.ktn-uk.co.uk/news/robotics-sector-deal-consultation |
| Description | UKRI research data capture approaches |
| Geographic Reach | National |
| Policy Influence Type | Contribution to new or improved professional practice |
| URL | https://www.researchprofessionalnews.com/rr-news-uk-research-councils-2023-1-researchfish-tweets-aga... |
| Description | (AAV-FACTORY) - Synthetic Viral Nanosystem for Highly Efficient AAV Manufacturing for Gene Therapy |
| Amount | € 150,000 (EUR) |
| Funding ID | 963992 |
| Organisation | European Commission |
| Sector | Public |
| Country | Belgium |
| Start | 02/2021 |
| End | 07/2022 |
| Description | 19-BBSRC-NSF/BIO. Leveraging synthetic biology to probe the rules of cell morphogenesis. |
| Amount | £805,498 (GBP) |
| Funding ID | BB/V004220/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2021 |
| End | 09/2026 |
| Description | 21ENGBIO Engineered orthogonal ribosomes for programmable protein modification |
| Amount | £100,755 (GBP) |
| Funding ID | BB/W012448/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 12/2023 |
| Description | 795867 NovoFold - De novo protein discovery as a tool for understanding the folding conundrum |
| Amount | € 183,454 (EUR) |
| Funding ID | 795867 |
| Organisation | European Commission |
| Sector | Public |
| Country | Belgium |
| Start | 01/2019 |
| End | 01/2021 |
| Description | A globally unique 19F, 13C, 15N NMR system to enable frontier bioscience |
| Amount | £689,881 (GBP) |
| Funding ID | BB/V019163/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2021 |
| End | 05/2022 |
| Description | A mechanistic framework for DNA recognition and cleavage by Type V CRISPR-Cas effector nucleases |
| Amount | £478,685 (GBP) |
| Funding ID | BB/S001239/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2019 |
| End | 09/2022 |
| Description | A pipeline for efficient recombination in wheat |
| Amount | £200,364 (GBP) |
| Funding ID | BB/W003317/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2021 |
| End | 03/2023 |
| Description | ADDovenom: Novel Snakebite Therapy Platform of Unparalleled Efficacy, Safety and Affordabillity |
| Amount | £3,199,663 (GBP) |
| Funding ID | 899670 |
| Organisation | European Union |
| Sector | Public |
| Country | European Union (EU) |
| Start | 09/2020 |
| End | 09/2024 |
| Description | ALERT 2016 (Schaffitzel) |
| Amount | £300,000 (GBP) |
| Funding ID | BB/R000484/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2017 |
| End | 08/2021 |
| Description | AMR Global Development Award 2017 |
| Amount | £88,000 (GBP) |
| Funding ID | MR/R014922/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2017 |
| End | 03/2018 |
| Description | Accelerate // Science Creates 2.0 |
| Amount | £498,646 (GBP) |
| Funding ID | 10106915 |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2024 |
| End | 02/2025 |
| Description | Advanced Grant (Mann) |
| Amount | € 2,100,000 (EUR) |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 09/2017 |
| End | 09/2022 |
| Description | Artist in residence (Toye) |
| Amount | £5,000 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 03/2017 |
| End | 07/2017 |
| Description | BBSRC David Phillips Fellowship (van der Kamp) |
| Amount | £1,015,015 (GBP) |
| Funding ID | BB/M026280/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2015 |
| End | 11/2020 |
| Description | BBSRC FTMA Fellowship with GenomeKey |
| Amount | £25,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2023 |
| End | 11/2023 |
| Description | BBSRC Flexible Talent Mobility Award (FTMA) |
| Amount | £25,000 (GGP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2019 |
| End | 12/2019 |
| Description | BBSRC GCRF: Natural product discovery and exploitation in Thailand (Race) |
| Amount | £19,850 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2016 |
| End | 02/2017 |
| Description | BBSRC IPC CASE award with Syngenta (Willis) |
| Amount | £96,696 (GBP) |
| Funding ID | BB/P504804/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 09/2020 |
| Description | BBSRC Impact Acceleration Account |
| Amount | £8,496 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2024 |
| End | 03/2024 |
| Description | BBSRC International Workshop: MaxSynBio bilateral (Mann) |
| Amount | £10,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2017 |
| End | 03/2018 |
| Description | BBSRC LoLa (Scrutton, Mulholland, vd Kamp) |
| Amount | £3,038,980 (GBP) |
| Funding ID | BB/M000354/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2015 |
| End | 04/2020 |
| Description | BBSRC Pathfinder Impact Acceleration Account Award |
| Amount | £9,978 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2023 |
| End | 03/2023 |
| Description | BBSRC Responsive Mode (Collinson) |
| Amount | £349,679 (GBP) |
| Funding ID | BB/M003604/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2014 |
| End | 02/2018 |
| Description | BBSRC Responsive Mode (Collinson) |
| Amount | £214,036 (GBP) |
| Funding ID | BB/N015126/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 11/2018 |
| Description | BBSRC SLoLa (Edwards) |
| Amount | £3,600,000 (GBP) |
| Funding ID | BB/N002628/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2016 |
| End | 12/2020 |
| Description | BBSRC Tools and Resources Development Fund (Collinson) |
| Amount | £547,203 (GBP) |
| Funding ID | BB/M012107/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2014 |
| End | 10/2015 |
| Description | BBSRC Tools and Techniques: Computational tools for enzyme engineering: bridging the gap between enzymologists and expert simulation |
| Amount | £146,027 (GBP) |
| Funding ID | BB/L018756/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2014 |
| End | 01/2016 |
| Description | BBSRC responsive mode (Anderson) |
| Amount | £474,945 (GBP) |
| Funding ID | BB/M02315X/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2015 |
| End | 11/2018 |
| Description | BBSRC sLoLa: Innovative Routes to Monoterpene Hydrocarbons and Their High Value Derivatives |
| Amount | £3,038,984 (GBP) |
| Funding ID | BB/M000354/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2010 |
| End | 09/2019 |
| Description | BEORHN: Bacterial Enzymatic Oxidation of Reactive Hydroxylamine in Nitrification via Combined Structural Biology and Molecular Simulation |
| Amount | £181,398 (GBP) |
| Funding ID | BB/V016768/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 12/2024 |
| Description | BP Research Innovation Fellowship (Simon Bennnie VR Lab) |
| Amount | £106,000 (GBP) |
| Organisation | BP (British Petroleum) |
| Sector | Private |
| Country | United Kingdom |
| Start | 03/2019 |
| End | 03/2021 |
| Description | Bio-inspired manufacturing of non-euclidean morphologies |
| Amount | £100,127 (GBP) |
| Funding ID | BB/W012324/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 01/2023 |
| Description | Biocatalysis and Biotransformation: A 5th Theme for the National Catalysis Hub |
| Amount | £3,053,639 (GBP) |
| Funding ID | EP/M013219/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2015 |
| End | 12/2019 |
| Description | BrisEngBio |
| Amount | £1,517,913 (GBP) |
| Funding ID | BB/W013959/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 01/2024 |
| Description | Bristol BioDesign Institute - BrisSynBio - Flexible Talent Mobility Account |
| Amount | £310,000 (GBP) |
| Funding ID | BB/S507891/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2018 |
| End | 03/2021 |
| Description | BristolBridge has contributed to the University of Bristol being the UK's largest recipient of RCUK AMR cross-council funding awards both in number (7) and value (£5.268M). 6 related AMR grants awarded with BristolBridge PIs/Co-Is include MRC-led AMR. |
| Amount | £5,268,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2016 |
| End | 09/2019 |
| Description | BristolBridge pump-priming (Willis) |
| Amount | £15,000 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2017 |
| End | 06/2017 |
| Description | CCP-BioSim: Biomolecular Simulation at the Life Sciences Interface |
| Amount | £235,706 (GBP) |
| Funding ID | EP/M022609/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2015 |
| End | 04/2021 |
| Description | CCP-BioSim: Biomolecular simulation at the life sciences interface |
| Amount | £287,541 (GBP) |
| Funding ID | EP/J010588/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2011 |
| End | 09/2015 |
| Description | CCPBioSim: Biomolecular Simulation at the Life Science Interface |
| Amount | £345,687 (FKP) |
| Funding ID | EP/T026308/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2020 |
| End | 10/2025 |
| Description | COMBO: CONTROL-BASED BIODESIGN OF MAMMALIAN CELL DYNAMICS |
| Amount | £1,478,668 (GBP) |
| Funding ID | EP/S01876X/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2019 |
| End | 09/2024 |
| Description | COMBO: CONTROL-BASED BIODESIGN OF MAMMALIAN CELL DYNAMICS (Marucci) |
| Amount | £1,444,092 (GBP) |
| Funding ID | EP/S01876X/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2019 |
| End | 03/2024 |
| Description | CYanoBacteria Engineering For Restoring Environments (CYBER) |
| Amount | £1,329,722 (GBP) |
| Funding ID | BB/Y007638/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2024 |
| End | 01/2026 |
| Description | Carbapenem Antibiotic Resistance in Enterobacteriaceae: Understanding Interactions of KPC Carbapenemases with Substrates and Inhibitors |
| Amount | £668,396 (GBP) |
| Funding ID | MR/T016035/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2020 |
| End | 01/2023 |
| Description | Coiled-coil Technology for Regulating Intracellular Protein-protein Interactions |
| Amount | £440,228 (GBP) |
| Funding ID | BB/V006231/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2021 |
| End | 10/2025 |
| Description | Colston Research Society Symposium in Synthetic Biology |
| Amount | £7,000 (GBP) |
| Organisation | Colston Research Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2016 |
| End | 11/2016 |
| Description | Confidence in Concept 'Developing a mobile device for rapid antimicrobial resistance detection in primary care' |
| Amount | £74,685 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2017 |
| End | 05/2018 |
| Description | Constructing catalytically proficient enzymes from de novo designed proteins |
| Amount | £509,889 (GBP) |
| Funding ID | BB/R016445/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2018 |
| End | 10/2022 |
| Description | CuPiD: A European Network in Computational Protein Design |
| Amount | £30,612 (GBP) |
| Funding ID | BB/T020105/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2021 |
| End | 08/2025 |
| Description | Custom nanomaterials from modular synthetic proteins |
| Amount | £1,151,785 (GBP) |
| Funding ID | EP/S017542/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2019 |
| End | 07/2024 |
| Description | Custom nanomaterials from modular synthetic proteins (Parmeggiani) |
| Amount | £1,124,171 (GBP) |
| Funding ID | EP/S017542/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2019 |
| End | 07/2024 |
| Description | DNA-DOCK (Advanced Grant Berger) |
| Amount | £2,048,016 (GBP) |
| Funding ID | 834631 |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 08/2019 |
| End | 08/2024 |
| Description | Defence and Security PhD call 2015 Synthetic Biology to Produce Novel Materials for Defence and Security (Trask / Perriman) |
| Amount | £544,000 (GBP) |
| Organisation | Defence Science & Technology Laboratory (DSTL) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2015 |
| End | 10/2019 |
| Description | Design and in vivo assembly of switchable protein-protein interactions for transcription regulation |
| Amount | £730,853 (GBP) |
| Funding ID | BB/S002820/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2018 |
| End | 11/2023 |
| Description | Dissecting the role of host receptor context and cytoskeletal disruption in malaria parasite invasion |
| Amount | £585,248 (GBP) |
| Funding ID | MR/V010506/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2021 |
| End | 08/2024 |
| Description | Dstl: Diels-Alderase based stimulous responsive self-healing materials (Race) |
| Amount | £117,077 (GBP) |
| Organisation | Defence Science & Technology Laboratory (DSTL) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2016 |
| End | 06/2017 |
| Description | EBI Discovery Research Support Grant |
| Amount | £6,795 (GBP) |
| Organisation | University of Bristol |
| Department | Elizabeth Blackwell Institute for Health Research |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 08/2022 |
| End | 12/2022 |
| Description | EEBio: Efficient Engineering And Control Of Predictable And Reliable Biosystems |
| Amount | £8,941,000 (GBP) |
| Funding ID | EP/Y014073/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2024 |
| End | 12/2029 |
| Description | EPSRC |
| Amount | £188,950 (GBP) |
| Funding ID | E/EP/G007705/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2013 |
| End | 03/2014 |
| Description | EPSRC Commercialisation Award |
| Amount | £49,331 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2024 |
| End | 05/2025 |
| Description | EPSRC Impact Acceleration Account 2016/17: Commercialisation of a novel peptide manufacturing platform (Race) |
| Amount | £15,000 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 07/2016 |
| End | 03/2017 |
| Description | EPSRC Impact Acceleration Account 2016/17: Innovation Programme (Race) |
| Amount | £25,752 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 07/2016 |
| End | 03/2017 |
| Description | EPSRC Institutional Sponsorship Award 2016/17: Bacterial-bot (Gorochowski) |
| Amount | £41,596 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 08/2016 |
| End | 03/2017 |
| Description | EPSRC Institutional Sponsorship Award 2016/17: SynBio VR (Glowacki) |
| Amount | £43,272 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 07/2016 |
| End | 09/2017 |
| Description | EPSRC Research Software Engineer Fellowship (Woods) |
| Amount | £487,166 (GBP) |
| Funding ID | EP/N018591/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2016 |
| End | 07/2021 |
| Description | EPSRC Responsive Mode (Perriman) |
| Amount | £357,292 (GBP) |
| Funding ID | EP/N026586/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2016 |
| End | 07/2019 |
| Description | EPSRC/GSK Industrial CASE studentship (Mann) |
| Amount | £75,000 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2014 |
| End | 04/2018 |
| Description | EU Marie Sklodowska Curie Fellowships (Mann) |
| Amount | € 137,200 (EUR) |
| Organisation | European Commission |
| Sector | Public |
| Country | Belgium |
| Start | 04/2015 |
| End | 05/2017 |
| Description | EVIDENCE (Toye) |
| Amount | £246,533 (GBP) |
| Funding ID | 860436 |
| Organisation | Marie Sklodowska-Curie Actions |
| Sector | Charity/Non Profit |
| Country | Global |
| Start | 09/2019 |
| End | 09/2023 |
| Description | EVO-NANO (Hauert) FET OPEN |
| Amount | £330,940 (GBP) |
| Funding ID | 800983 |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 05/2018 |
| End | 05/2021 |
| Description | Engineering Biology Centre for Doctoral Training |
| Amount | £8,974,478 (GBP) |
| Funding ID | EP/Y034791/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2024 |
| End | 08/2032 |
| Description | Engineering Biology FTMA |
| Amount | £315,127 (GBP) |
| Funding ID | BB/Z515140/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2024 |
| End | 03/2027 |
| Description | Engineering for a prosperous nation (Marucci) |
| Amount | £309,807 (GBP) |
| Funding ID | EP/R02815X/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2018 |
| End | 05/2019 |
| Description | Engineering inducible anhydrides for irreversible Red Blood Cell enzyme decoration |
| Amount | £848,040 (GBP) |
| Funding ID | EP/W01565X/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2022 |
| End | 01/2022 |
| Description | Enterprise and Impact Development Fund (Whitney) |
| Amount | £15,000 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 03/2017 |
| End | 10/2017 |
| Description | European Commission FP7 collaboration (Berger) |
| Amount | € 5,233,492 (EUR) |
| Organisation | European Commission |
| Sector | Public |
| Country | Belgium |
| Start | 11/2014 |
| End | 11/2017 |
| Description | Extension |
| Amount | $200,000 (USD) |
| Organisation | ONRG Office of Naval Research Global |
| Sector | Public |
| Country | United States |
| Start | 11/2022 |
| End | 09/2024 |
| Description | Flexible talent Mobility Award (FTMA) |
| Amount | £130,000 (GBP) |
| Funding ID | BB/R506539/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2017 |
| End | 03/2019 |
| Description | From de novo peptide assemblies to designed organelles in living cells |
| Amount | £410,000 (GBP) |
| Funding ID | RPG-2021-049 |
| Organisation | The Leverhulme Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 06/2021 |
| End | 06/2024 |
| Description | Future Emerging Technologies |
| Amount | € 3,000,000 (EUR) |
| Organisation | European Commission H2020 |
| Sector | Public |
| Country | Belgium |
| Start | 09/2017 |
| End | 09/2020 |
| Description | GSK collaboration (Enzyme - SAGEs) |
| Amount | £120,000 (GBP) |
| Funding ID | 100038043 |
| Organisation | GlaxoSmithKline (GSK) |
| Sector | Private |
| Country | Global |
| Start | 04/2014 |
| End | 11/2015 |
| Description | GSK collaboration (Enzyme - SAGEs): Extension |
| Amount | £117,000 (GBP) |
| Organisation | GlaxoSmithKline (GSK) |
| Sector | Private |
| Country | Global |
| Start | 05/2016 |
| End | 07/2017 |
| Description | Haemotoxic and cytotoxic snake venom metalloproteinases - production, enzymatic specificity, snakebite treatment, and biomedical use |
| Amount | £1,304,514 (GBP) |
| Funding ID | BB/Y007581/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2024 |
| End | 01/2026 |
| Description | IB Catalyst |
| Amount | £247,085 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2015 |
| End | 03/2016 |
| Description | Impact Acceleration Award (Burston) |
| Amount | £28,282 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2017 |
| End | 05/2018 |
| Description | Impact Acceleration Award (Perriman/CytoSeek) |
| Amount | £14,000 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2017 |
| End | 03/2018 |
| Description | Industrial Biotechnology Catalyst (Burston) |
| Amount | £91,271 (GBP) |
| Funding ID | BB/M028186/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2015 |
| End | 03/2016 |
| Description | Industrial collaboration (Berger) |
| Amount | £418,000 (GBP) |
| Organisation | GE Healthcare Limited |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 03/2018 |
| End | 03/2020 |
| Description | Innovation and Knowledge Centre in Synthetic Biology (Co-I on application) |
| Amount | £5,074,187 (GBP) |
| Funding ID | EP/L011573/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2013 |
| End | 09/2018 |
| Description | Inquire: Software for real-time analysis of binding |
| Amount | £105,748 (GBP) |
| Funding ID | BB/K016601/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2013 |
| End | 09/2014 |
| Description | Institute Strategic Programme |
| Amount | £1,200,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2017 |
| End | 03/2022 |
| Description | International workshops |
| Amount | £10,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2019 |
| End | 08/2019 |
| Description | Investor accelerator (CytoSeek) |
| Amount | £148,000 (GBP) |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2018 |
| End | 06/2019 |
| Description | JGI Seedcorn Funding |
| Amount | £10,000 (GBP) |
| Organisation | University of Bristol |
| Department | Jean Golding Institute |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 03/2023 |
| End | 05/2023 |
| Description | MRC AMR (Bailey) |
| Amount | £2,500,000 (GBP) |
| Funding ID | MR/N029909/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2016 |
| End | 05/2020 |
| Description | MRC Confidence in Concepts Award |
| Amount | £25,000 (GBP) |
| Funding ID | MC_PC_15041 |
| Organisation | Medical Research Council (MRC) |
| Department | MRC Confidence in Concept Scheme |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2016 |
| End | 08/2017 |
| Description | MRC New Investigator Research Grant (Marucci) |
| Amount | £518,777 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2016 |
| End | 05/2019 |
| Description | Manufacturing of affordable pharmaceuticals to prevent and treat cancers, obesity and age-related diseases (Race) |
| Amount | £100,000 (GBP) |
| Funding ID | Unknown |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2018 |
| End | 11/2019 |
| Description | Marie Sklodowska-Curie Fellowship |
| Amount | £192,297 (GBP) |
| Organisation | Marie Sklodowska-Curie Actions |
| Sector | Charity/Non Profit |
| Country | Global |
| Start | 05/2024 |
| End | 06/2026 |
| Description | Max Planck Centre for Minimal Biology |
| Amount | £9,600,000 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 07/2019 |
| End | 07/2024 |
| Description | Mechanism and design of a pH sensor at the organelle-cytoskeleton interface |
| Amount | £788,527 (GBP) |
| Funding ID | BB/W005581/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2022 |
| End | 01/2025 |
| Description | Metabiogel Absorber |
| Amount | £118,600 (GBP) |
| Organisation | Defence Science & Technology Laboratory (DSTL) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2023 |
| End | 10/2024 |
| Description | Microsoft Research PhD Studentship (Gorochowski) |
| Amount | £859,000 (GBP) |
| Funding ID | EP/T51763X/1 |
| Organisation | Microsoft Research |
| Sector | Private |
| Country | Global |
| Start | 08/2019 |
| End | 08/2022 |
| Description | Molecular Photonic Breadboards |
| Amount | £7,255,282 (GBP) |
| Funding ID | EP/T012455/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2020 |
| End | 05/2026 |
| Description | Nanomaterial delivered switches to control synthetic cassettes in plants |
| Amount | £100,127 (GBP) |
| Funding ID | BB/W012324/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 01/2023 |
| Description | National Institute of Health Research Biomedical Research Unit (Toye) |
| Amount | £3,000,000 (GBP) |
| Organisation | National Institute for Health and Care Research |
| Department | NIHR Biomedical Research Centre |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2015 |
| End | 10/2020 |
| Description | New Industrial Systems (Race) |
| Amount | £2,710,000 (GBP) |
| Funding ID | EP/R020957/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2017 |
| End | 11/2020 |
| Description | Next generation DNA synthesis (Race) |
| Amount | £2,219,000 (GBP) |
| Funding ID | BB/M025624/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2015 |
| End | 02/2016 |
| Description | Nicotinic Ligand Development to Target Smoking Cessation and Gain a Molecular Level Understanding of Partial Agonism |
| Amount | £724,553 (GBP) |
| Funding ID | EP/N024117/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2016 |
| End | 11/2019 |
| Description | Oracle for Research Cloud Fellowship |
| Amount | $100,000 (USD) |
| Organisation | Oracle Corporation |
| Sector | Private |
| Country | United States |
| Start | 02/2023 |
| End | 12/2023 |
| Description | PREDACTED Predictive computational models for Enzyme Dynamics, Antimicrobial resistance, Catalysis and Thermoadaptation for Evolution and Desig |
| Amount | € 2,482,332 (EUR) |
| Funding ID | 101021207 |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 09/2021 |
| End | 09/2026 |
| Description | Phase 2 - Engineered red blood cells with enhanced compatibility and storage properties (Toye) |
| Amount | £250,000 (GBP) |
| Organisation | Defence Science & Technology Laboratory (DSTL) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2019 |
| End | 06/2021 |
| Description | Precision Docking of Very Large DNA Cargos in Mammalian Genomes (DNA-DOCK) |
| Amount | € 2,498,578 (EUR) |
| Funding ID | 834631 |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 08/2019 |
| End | 08/2024 |
| Description | Programmed assembly of protocellular materials |
| Amount | £392,155 (GBP) |
| Funding ID | EP/T01508X/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2020 |
| End | 06/2023 |
| Description | Proof of Concept (Perriman) |
| Amount | £70,000 (GBP) |
| Organisation | SynbiCITE |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 02/2018 |
| End | 10/2018 |
| Description | Proof of Concept (Woolfson) |
| Amount | € 135,000 (EUR) |
| Organisation | European Commission H2020 |
| Sector | Public |
| Country | Belgium |
| Start | 03/2018 |
| End | 09/2019 |
| Description | Proximity to Discovery (Boyce) |
| Amount | £3,500 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2017 |
| End | 05/2017 |
| Description | Research Project Grant |
| Amount | £140,582 (GBP) |
| Funding ID | RPG-2016-147 |
| Organisation | The Leverhulme Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2017 |
| End | 12/2019 |
| Description | Research fellow Enhancement Award (Gorochowski) |
| Amount | £81,200 (GBP) |
| Organisation | The Royal Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 12/2017 |
| End | 03/2021 |
| Description | Responsive Mode (Mann) |
| Amount | £706,499 (GBP) |
| Funding ID | BB/P017320/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2017 |
| End | 09/2020 |
| Description | Responsive Mode (Willis) |
| Amount | £725,000 (GBP) |
| Funding ID | BB/R007853/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2018 |
| End | 03/2021 |
| Description | Responsive mode (Woolfson) |
| Amount | £878,290 (GBP) |
| Funding ID | BB/R00661X/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2018 |
| End | 12/2021 |
| Description | Royal Society for Engineering Enterprise fellowship (Carter) |
| Amount | £42,548 (GBP) |
| Organisation | Royal Academy of Engineering |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2018 |
| End | 03/2019 |
| Description | Specialist Research Institute (Woolfson) |
| Amount | £45,000 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 01/2017 |
| End | 07/2019 |
| Description | Specialist Research Institute: Bristol BioDesign Institute |
| Amount | £45,000 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 01/2017 |
| End | 07/2019 |
| Description | Supercharged protein-surfactant bioconjugates for next-generation cell therapies |
| Amount | £934,902 (GBP) |
| Funding ID | MR/S016430/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2019 |
| End | 04/2023 |
| Description | SynbiCITE 2.0 |
| Amount | £3,058,262 (GBP) |
| Funding ID | EP/S001859/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2018 |
| End | 09/2024 |
| Description | SynbiCITE poof of concept award |
| Amount | £50,000 (GBP) |
| Funding ID | EP/L011573/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2014 |
| End | 05/2015 |
| Description | Synthetic Biology Centre for Doctoral Training (Co-I) |
| Amount | £4,705,815 (GBP) |
| Funding ID | EP/L016494/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2014 |
| End | 09/2022 |
| Description | Synthetic biology for growth: SynBio CDT equipment (Co-I) |
| Amount | £134,262 (GBP) |
| Funding ID | EP/J013501/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2014 |
| End | 12/2014 |
| Description | Synthetic biology for transparent materials (Race) |
| Amount | £93,253 (GBP) |
| Funding ID | ACC101800 |
| Organisation | Defence Science & Technology Laboratory (DSTL) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2017 |
| End | 05/2018 |
| Description | Translational award (Zentraxa) |
| Amount | £100,000 (GBP) |
| Funding ID | 133271 |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2018 |
| End | 09/2018 |
| Description | Understanding supply and demand for heme in cells |
| Amount | £750,000 (GBP) |
| Funding ID | BB/W007908/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2022 |
| End | 03/2026 |
| Description | University Research Fellowsip (Gorochowski) |
| Amount | £532,040 (GBP) |
| Organisation | The Royal Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2017 |
| End | 09/2022 |
| Description | University of Bristol EPSRC Institutional Support Award |
| Amount | £30,000 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 08/2015 |
| End | 03/2016 |
| Description | Unlocking the potential of engineered C-C bond forming enzymes for biocatalysis |
| Amount | £770,153 (GBP) |
| Funding ID | BB/T001968/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2019 |
| End | 09/2024 |
| Description | UoB BBSRC IAA GCRF: Bristol - Thailand Vaccine technology development (Davidson) |
| Amount | £24,220 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 11/2016 |
| End | 03/2017 |
| Description | UoB Impact Acceleration Award (Davidson) |
| Amount | £10,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2017 |
| End | 02/2018 |
| Description | UoB International Strategic Fund: MaxSynBio bilateral (Mann) |
| Amount | £5,000 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 03/2017 |
| End | 03/2018 |
| Description | Using hydrodynamics and geometry to design bacteriaphobic surfaces (Bennett) |
| Amount | £400,000 (GBP) |
| Organisation | University of Bristol |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 11/2018 |
| End | 10/2021 |
| Description | Vaccine Manufacturing Research Hub (Berger) |
| Amount | £10,000,000 (GBP) |
| Funding ID | EP/R013764/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2017 |
| End | 03/2021 |
| Description | Wellcome Investigator Award (Collinson) |
| Amount | £1,506,091 (GBP) |
| Funding ID | 104632/Z/14/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2014 |
| End | 09/2020 |
| Description | Wellcome Multi-User Equipment: CryoEM (Schaffitzel) |
| Amount | £2,314,580 (GBP) |
| Funding ID | 110084/Z/15/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2016 |
| End | 08/2021 |
| Description | emPOWER: in-body artificial muscles for physical augmentation, function restoration, patient empowerment and future healthcare |
| Amount | £6,142,804 (GBP) |
| Funding ID | EP/T020792/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2021 |
| End | 08/2026 |
| Description | https://gtr.ukri.org/person/2A2990B1-E1E1-4888-8848-7C256C3A3B43 |
| Amount | £20,009,000 (GBP) |
| Funding ID | https://gtr.ukri.org/person/2A2990B1-E1E1-4888-8848-7C256C3A3B43 |
| Organisation | United Kingdom Research and Innovation |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2006 |
| End | 02/2033 |
| Title | A HIGH-RESOLUTION LUMINESCENT ASSAY FOR RAPID AND CONTINUOUS MONITORING OF PROTEIN TRANSLOCATION ACROSS BIOLOGICAL MEMBRANES |
| Description | Protein translocation is a fundamental process in biology. Major gaps in our understanding of this process arise due the poor sensitivity, low time-resolution and irreproducibility of translocation assays. To address this, we applied NanoLuc split-luciferase to produce a new strategy for measuring protein transport. The system reduces the timescale of data collection from days to minutes, and allows continuous acquisition with a time-resolution in the order of seconds - yielding kinetics parameters suitable for mechanistic elucidation and mathematical fitting. To demonstrate its versatility, we implemented and validated the assay in vitro and in vivo for the bacterial Sec system, and the mitochondrial protein import apparatus. Overall, this technology represents a major step forward, providing a powerful new tool for fundamental mechanistic enquiry of protein translocation and for inhibitor (drug) screening, with an intensity and rigour unattainable through classical methods. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | see paper Pereira, G.C., Allen, W.J., Watkins, D.W., Buddrus, L., Noone, D., Liu, X., Richardson, A.P., Chacinska, A. and Collinson, I. (2019) A high-resolution luminescent assay for rapid and continuous monitoring of protein translocation across biological membranes: bioRxiv - https://doi.org/10.1101/456921 In Press at J. Mol. Biol |
| URL | https://doi.org/10.1101/456921 |
| Title | An expandable, modular de novo protein platform for precision redox engineering |
| Description | Pioneering study signals new era of environment-friendly programmable bioelectronics Image shows the design of a protein nanowire, with the green arrow indicating electron flow. Ross Anderson Image shows structural analysis of the protein-based wire, comparing the model of the designed protein (shown in red) with the experimentally determined structure (in grey). Ross Anderson Press release issued: 25 July 2023 Researchers have created a unique microscopic toolkit of 'green' tuneable electrical components, paving the way for a new generation of bioelectronic devices and sensors. The University of Bristol-led study, published today in The Proceedings of the National Academy of Sciences (PNAS), demonstrates how to make conductive, biodegradable wires from designed proteins. These could be compatible with conventional electronic components made from copper or iron, as well as the biological machinery responsible for generating energy in all living organisms. The miniscule wires are the size of transistors on silicon chips or one thousandth of the breadth of the finest human hair. They are made completely of natural amino acids and heme molecules, found in proteins such as hemoglobin, which transports oxygen in red blood cells. Harmless bacteria were used for their manufacture, eliminating the need for potentially complex and environmentally damaging procedures commonly used in the production of synthetic molecules. Lead author Ross Anderson, Professor of Biological Chemistry at the University of Bristol, said: "While our designs take inspiration from the protein-based electronic circuits necessary for all life on Earth, they are free from much of the complexity and instability that can prevent the exploitation of their natural equivalents on our own terms. We can also build these minute electronic components to order, specifying their properties in a way that is not possible with natural proteins." Leading experts in biomolecular engineering and simulation worked together to produce this unique new method of designing tailor-made proteins with tuneable electronic properties. The multidisciplinary team used advanced computational tools to design simple building blocks that could be combined into longer, wire-like protein chains for conducting electrons. They were able to visualise the structures of these wires using protein X-ray crystallography and electron cryo-microscopy (cryo-EM), techniques which allow structures to be viewed in the finest detail. Pushing the technical boundaries of cryo-EM, images of the smallest individual protein ever studied were obtained with this technique. Ultimately, these nanoscale designer wires have the potential to be used in a wide range of applications, including biosensors for the diagnosis of diseases and detection of environmental pollutants. It is also hoped this invention will form the foundation of new electrical circuits for creating tailor-made catalysts for green industrial biotechnology and artificial photosynthetic proteins for capturing solar energy. The breakthrough was possible thanks to a £4.9 million grant from the Biotechnology and Biological Science Research Council (BBSRC), the UK's largest bioscience funder, which resulted in a five-year project entitled 'The Circuits of Life' involving the Universities of Bristol, Portsmouth, East Anglia, and University College London (UCL). The team harnessed their expertise in protein design, electron transfer, biomolecular simulation, structural biology and spectroscopy, gaining insight into how electrons flow through natural biological molecules, a fundamental process which underpins cellular respiration and photosynthesis. Further advances are expected as the project, which began last year, progresses, presenting significant opportunities to help meet the transition to net zero and more sustainable industrial processes. Co-author Adrian Mulholland, Professor of Chemistry at the University of Bristol, said: "These proteins show how protein design is increasingly delivering practically useful tools. They offer exciting possibilities as components for engineering biology and also are great systems for investigating the fundamental mechanisms of biological electron transfer." Paper 'An expandable, modular de novo protein platform for precision redox engineering' by George H. Hutchins, Claire E.M. Noble, Adrian Bunzel et al published in PNAS |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | Pioneering study signals new era of environment-friendly programmable bioelectronics Image shows the design of a protein nanowire, with the green arrow indicating electron flow. Ross Anderson Image shows structural analysis of the protein-based wire, comparing the model of the designed protein (shown in red) with the experimentally determined structure (in grey). Ross Anderson Press release issued: 25 July 2023 Researchers have created a unique microscopic toolkit of 'green' tuneable electrical components, paving the way for a new generation of bioelectronic devices and sensors. The University of Bristol-led study, published today in The Proceedings of the National Academy of Sciences (PNAS), demonstrates how to make conductive, biodegradable wires from designed proteins. These could be compatible with conventional electronic components made from copper or iron, as well as the biological machinery responsible for generating energy in all living organisms. The miniscule wires are the size of transistors on silicon chips or one thousandth of the breadth of the finest human hair. They are made completely of natural amino acids and heme molecules, found in proteins such as hemoglobin, which transports oxygen in red blood cells. Harmless bacteria were used for their manufacture, eliminating the need for potentially complex and environmentally damaging procedures commonly used in the production of synthetic molecules. Lead author Ross Anderson, Professor of Biological Chemistry at the University of Bristol, said: "While our designs take inspiration from the protein-based electronic circuits necessary for all life on Earth, they are free from much of the complexity and instability that can prevent the exploitation of their natural equivalents on our own terms. We can also build these minute electronic components to order, specifying their properties in a way that is not possible with natural proteins." Leading experts in biomolecular engineering and simulation worked together to produce this unique new method of designing tailor-made proteins with tuneable electronic properties. The multidisciplinary team used advanced computational tools to design simple building blocks that could be combined into longer, wire-like protein chains for conducting electrons. They were able to visualise the structures of these wires using protein X-ray crystallography and electron cryo-microscopy (cryo-EM), techniques which allow structures to be viewed in the finest detail. Pushing the technical boundaries of cryo-EM, images of the smallest individual protein ever studied were obtained with this technique. Ultimately, these nanoscale designer wires have the potential to be used in a wide range of applications, including biosensors for the diagnosis of diseases and detection of environmental pollutants. It is also hoped this invention will form the foundation of new electrical circuits for creating tailor-made catalysts for green industrial biotechnology and artificial photosynthetic proteins for capturing solar energy. The breakthrough was possible thanks to a £4.9 million grant from the Biotechnology and Biological Science Research Council (BBSRC), the UK's largest bioscience funder, which resulted in a five-year project entitled 'The Circuits of Life' involving the Universities of Bristol, Portsmouth, East Anglia, and University College London (UCL). The team harnessed their expertise in protein design, electron transfer, biomolecular simulation, structural biology and spectroscopy, gaining insight into how electrons flow through natural biological molecules, a fundamental process which underpins cellular respiration and photosynthesis. Further advances are expected as the project, which began last year, progresses, presenting significant opportunities to help meet the transition to net zero and more sustainable industrial processes. Co-author Adrian Mulholland, Professor of Chemistry at the University of Bristol, said: "These proteins show how protein design is increasingly delivering practically useful tools. They offer exciting possibilities as components for engineering biology and also are great systems for investigating the fundamental mechanisms of biological electron transfer." Paper 'An expandable, modular de novo protein platform for precision redox engineering' by George H. Hutchins, Claire E.M. Noble, Adrian Bunzel et al published in PNAS |
| URL | https://www.bristol.ac.uk/news/2023/july/protein-nanowires.html |
| Title | Breeders tool kit meeting |
| Description | Novel wheat lines and novel wheat molecular markers to be transferred to the commercial sector |
| Type Of Material | Biological samples |
| Year Produced | 2018 |
| Provided To Others? | No |
| Impact | Novel materials and markers to be supplied to the wheat breeding community |
| Title | COVID is airborne |
| Description | Multscale model of SARS-CoV-2 in respiratory aerosol |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | HPC2021 Gordon Bell Special Prize Finalist Skip to main content U.S. flagAn official website of the United States government Here's how you know NIH NLM Logo Log in Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation Search PMC Full-Text Archive Search in PMC Run this search in PubMed Advanced Search User Guide Journal List SAGE Choice PMC9527558 Logo of sageopen The International Journal of High Performance Computing Applications Int J High Perform Comput Appl. 2023 Jan; 37(1): 28-44. Published online 2022 Oct 2. doi: 10.1177/10943420221128233 PMCID: PMC9527558 PMID: 36647365 #COVIDisAirborne: AI-enabled multiscale computational microscopy of delta SARS-CoV-2 in a respiratory aerosol Monitoring Editor: Mark Parsons Abigail Dommer,1,†Lorenzo Casalino,1,†Fiona Kearns,1,†Mia Rosenfeld,1 Nicholas Wauer,1 Surl-Hee Ahn,1 John Russo,2 Sofia Oliveira,3 Clare Morris,1 Anthony Bogetti,4 Anda Trifan,5,6 Alexander Brace,5,7 Terra Sztain,1,8 Austin Clyde,5,7 Heng Ma,5 Chakra Chennubhotla,4 Hyungro Lee,9 Matteo Turilli,9 Syma Khalid,10 Teresa Tamayo-Mendoza,11 Matthew Welborn,11 Anders Christensen,11 Daniel GA Smith,11 Zhuoran Qiao,12 Sai K Sirumalla,11 Michael O'Connor,11 Frederick Manby,11 Anima Anandkumar,12,13 David Hardy,6 James Phillips,6 Abraham Stern,13 Josh Romero,13 David Clark,13 Mitchell Dorrell,14 Tom Maiden,14 Lei Huang,15 John McCalpin,15 Christopher Woods,3 Alan Gray,13 Matt Williams,3 Bryan Barker,16 Harinda Rajapaksha,16 Richard Pitts,16 Tom Gibbs,13 John Stone,6,13 Daniel M. Zuckerman,2 Adrian J. Mulholland,3 Thomas Miller, III,11,12 Shantenu Jha,9 Arvind Ramanathan,5 Lillian Chong,4 and Rommie E Amaro1 Author information Copyright and License information Disclaimer Previous version available: This article is based on a previously available preprint: "#COVIDisAirborne: AI-Enabled Multiscale Computational Microscopy of Delta SARS-CoV-2 in a Respiratory Aerosol". Go to: Abstract We seek to completely revise current models of airborne transmission of respiratory viruses by providing never-before-seen atomic-level views of the SARS-CoV-2 virus within a respiratory aerosol. Our work dramatically extends the capabilities of multiscale computational microscopy to address the significant gaps that exist in current experimental methods, which are limited in their ability to interrogate aerosols at the atomic/molecular level and thus obscure our understanding of airborne transmission. We demonstrate how our integrated data-driven platform provides a new way of exploring the composition, structure, and dynamics of aerosols and aerosolized viruses, while driving simulation method development along several important axes. We present a series of initial scientific discoveries for the SARS-CoV-2 Delta variant, noting that the full scientific impact of this work has yet to be realized. Keywords: molecular dynamics, deep learning, multiscale simulation, weighted ensemble, computational virology, SARS-CoV-2, aerosols, COVID-19, HPC, AI, GPU, Delta Go to: Justification We develop a novel HPC-enabled multiscale research framework to study aerosolized viruses and the full complexity of species that comprise them. We present technological and methodological advances that bridge time and length scales from electronic structure through whole aerosol particle morphology and dynamics. Performance attributes Performance attribute Our submission Category of achievement Scalability, Time-to-solution Type of method used Explicit, Deep Learning Results reported on the basis of Whole application including I/O Precision reported Mixed Precision System scale Measured on full system Measurement mechanism Hardware performance counters Application timers Performance Modeling Open in a separate window Overview of the problem Respiratory pathogens, such as SARS-CoV-2 and influenza, are the cause of significant morbidity and mortality worldwide. These respiratory pathogens are spread by virus-laden aerosols and droplets that are produced in an infected person, exhaled, and transported through the environment (Wang et al., 2021) (Figure 1). Medical dogma has long focused on droplets as the main transmission route for respiratory viruses, where either a person has contact with an infected surface (fomites) or direct droplet transmission by close contact with an infected individual. However, as we continue to observe with SARS-CoV-2, airborne transmission also plays a significant role in spreading disease. We know this from various super spreader events, for example, during a choir rehearsal (Miller et al., 2021). Intervention and mitigation decisions, such as the relative importance of surface cleaning or whether and when to wear a mask, have unfortunately hinged on a weak understanding of aerosol transmission, to the detriment of public health. An external file that holds a picture, illustration, etc. Object name is 10.1177_10943420221128233-fig1.jpg Figure 1. Overall schematic depicting the construction and multiscale simulations of Delta SARS-CoV-2 in a respiratory aerosol. (N.B.: The size of di-valent cations has been increased for visibility.) A central challenge to understanding airborne transmission has been the inability of experimental science to reliably probe the structure and dynamics of viruses once they are inside respiratory aerosol particles. Single particle experimental methods have poor resolution for smaller particles (<1 micron) and are prone to sample destruction during collection. Airborne viruses are present in low concentrations in the air and are similarly prone to viral inactivation during sampling. In addition, studies of the initial infection event, for example, in the deep lung, are limited in their ability to provide a detailed understanding of the myriad of molecular interactions and dynamics taking place in situ. Altogether, these knowledge gaps hamper our collective ability to understand mechanisms of infection and develop novel effective antivirals, as well as prevent us from developing concrete, science-driven mitigation measures (e.g., masking and ventilation protocols). Here, we aim to reconceptualize current models of airborne transmission of respiratory viruses by providing never-before-seen views of viruses within aerosols. Our approach relies on the use of all-atom molecular dynamics (MD) simulations as a multiscale "computational microscope." MD simulations can synthesize multiple types of biological data (e.g., multiresolution structural datasets, glycomics, lipidomics, etc.) into cohesive, biologically "accurate" structural models. Once created, we then approximate the model down to its many atoms, creating trajectories of its time dependent dynamics under cell-like (or in this case, aerosol-like) conditions. Critically, MD simulations are more than just "pretty movies." MD equations are solved in a theoretically rigorous manner, allowing us to compute experimentally testable macroscopic observables from time-averaged microscopic properties. What this means is that we can directly connect MD simulations with experiments, each validating and providing testable hypotheses to the other, which is the real power of the approach. An ongoing challenge to the successful application of such methods, however, is the need for technological and methodological advances that make it possible to access length scales relevant to the study of large, biologically complex systems (spanning nanometers to ~one micron in size) and, correspondingly, longer timescales (microseconds to seconds). Such challenges and opportunities manifest in the study of aerosolized viruses. Aerosols are generally defined as being less than 5 microns in diameter, able to float in the air for hours, travel significant distances (i.e., can fill a room, like cigarette smoke), and be inhaled. Fine aerosols < 1 micron in size can stay in the air for over 12 h and are enriched with viral particles (Fennelly 2020; Coleman et al., 2021). Our work focuses on these finer aerosols that travel deeper into the respiratory tract. Several studies provide the molecular recipes necessary to reconstitute respiratory aerosols according to their actual biologically relevant composition (Vejerano and Marr 2018; Walker et al., 2021). These aerosols can contain lipids, cholesterol, albumin (protein), various mono- and di-valent salts, mucins, other surfactants, and water (Figure 1). Simulations of aerosolized viruses embody a novel framework for the study of aerosols: they will allow us and others to tune different species, relative humidity, ion concentrations, etc. to match experiments that can directly and indirectly connect to and inform our simulations, as well as test hypotheses. Some of the species under study here, for example, mucins, have not yet been structurally characterized or explored with simulations and thus the models we generate are expected to have impact beyond their roles in aerosols. In addition to varying aerosol composition and size, the viruses themselves can be modified to reflect new variants of concern, where such mutations may affect interactions with particular species in the aerosol that might affect its structural dynamics and/or viability. The virion developed here is the Delta variant (B.1.617.2 lineage) of SARS-CoV-2 (Figure 2), which presents a careful integration of multiple biological datasets: (1) a complete viral envelope with realistic membrane composition, (2) fully glycosylated full-length spike proteins integrating 3D structural coordinates from multiple cryoelectron microscopy (cryoEM) studies (McCallum et al., 2021; Wrapp et al., 2020; Walls et al., 2020; Bangaru et al., 2020) (3) all biologically known features (post-translational modifications, palmitoylation, etc.), (4) any other known membrane proteins (e.g. the envelope (E) and membrane (M) proteins), and (5) virion size and patterning taken directly from cryoelectron tomography (cryoET). Each of the individual components of the virus are built up before being integrated into the composite virion, and thus represent useful molecular-scale scientific contributions in their own right (Casalino et al., 2020; Sztain et al., 2021). An external file that holds a picture, illustration, etc. Object name is 10.1177_10943420221128233-fig2.jpg Figure 2. Individual protein components of the SARS-CoV-2 Delta virion. The spike is shown with the surface in cyan and with Delta's mutated residues and deletion sites highlighted in pink and yellow, respectively. Glycans attached to the spike are shown in blue. The E protein is shown in yellow and the M-protein is shown in silver and white. Visualized with VMD. Altogether in this work, we dramatically extend the capabilities of data-driven, multiscale computational microscopy to provide a new way of exploring the composition, structure, and dynamics of respiratory aerosols. While a seemingly limitless number of putative hypotheses could result from these investigations, the first set of questions we expect to answer are: How does the virus exist within a droplet of the same order of magnitude in size, without being affected by the air-water interface, which is known to destroy molecular structure (D'Imprima et al. 2019)? How does the biochemical composition of the droplet, including pH, affect the structural dynamics of the virus? Are there species within the aerosols that "buffer" the viral structure from damage, and are there particular conditions under which the impact of those species changes? Our simulations can also provide specific parameters that can be included in physical models of aerosols, which still assume a simple water or water-salt composition even though it is well known that such models, for example, using kappa-Kohler theory, break down significantly as the molecular species diversify (Petters and Kreidenweis 2007). Go to: Current state of the art Current experimental methods are unable to directly interrogate the atomic-level structure and dynamics of viruses and other molecules within aerosols. Here we showcase computational microscopy as a powerful tool capable to overcome these significant experimental limitations. We present the major elements of our multiscale computational microscope and how they come together in an integrated manner to enable the study of aerosols across multiple scales of resolution. We demonstrate the impact such methods can bring to bear on scientific challenges that until now have been intractable, and present a series of new scientific discoveries for SARS-CoV-2. Parallel molecular dynamics All-atom molecular dynamics simulation has emerged as an increasingly powerful tool for understanding the molecular mechanisms underlying biophysical behaviors in complex systems. Leading simulation engines, NAMD (Phillips et al., 2020), AMBER (Case et al. [n. d.]), and GROMACS (Páll et al., 2020), are broadly useful, with each providing unique strengths in terms of specific methods or capabilities as required to address a particular biological question, and in terms of their support for particular HPC hardware platforms. Within the multiscale computational microscopy platform developed here, we show how each of these different codes contributes different elements to the overall framework, oftentimes utilizing different computing modalities/architectures, while simultaneously extending on state-of-the-art for each. Structure building, simulation preparation, visualization, and post hoc trajectory analysis are performed using VMD on both local workstations and remote HPC resources, enabling modeling of the molecular systems studied herein (Humphrey et al., 1996; Stone et al., 2013a,b, 2016b; Sener et al., 2021). We show how further development of each of these codes, considered together within the larger-scale collective framework, enables the study of SARS-CoV-2 in a wholly novel manner, with extension to numerous other complex systems and diseases. AI-enhanced WE simulations Because the virulence of the Delta variant of SARS-CoV-2 may be partly attributable to spike protein (S) opening, it is of pressing interest to characterize the mechanism and kinetics of the process. Although S-opening in principle can be studied via conventional MD simulations, in practice the system complexity and timescales make this wholly intractable. Splitting strategies that periodically replicate promising MD trajectories, among them the weighted ensemble (WE) method (Huber and Kim 1996; Zuckerman and Chong 2017), have enabled simulations of the spike opening of WT SARS-CoV-2 (Sztain et al., 2021; Zimmerman et al., 2021). WE simulations can be orders of magnitude more efficient than conventional MD in generating pathways and rate constants for rare events (e.g. protein folding (Adhikari et al., 2019) and binding (Saglam and Chong 2019)). The WESTPA software for running WE (Zwier et al., 2015) is well-suited for high-performance computing with nearly perfect CPU/GPU scaling. The software is interoperable with any dynamics engine, including the GPU-accelerated AMBER dynamics engine (Salomon-Ferrer et al., 2013) that is used here. As shown below, major upgrades to WESTPA (v. 2.0) have enabled a dramatic demonstration of spike opening in the Delta variant (Figures 5 and and6)6) and exponentially improved analysis of spike-opening kinetics (Russo et al., 2022). An external file that holds a picture, illustration, etc. Object name is 10.1177_10943420221128233-fig5.jpg Figure 5. Delta variant spike opening from WE simulations, and AI/haMSM analysis. A) The integrated workflow. B) Snapshots of the "down," "up," and "open" states for Delta S-opening from a representative pathway generated by WE simulation, which represents ~ 105 speedup compared to conventional MD. C) Rate constant estimation with haMSM analysis of WE data (purple lines) significantly improves direct WE computation (red), by comparison to experimental measurement (black dashed). Varying haMSM estimates result from different featurizations which will be individually cross-validated. D) The first three dimensions of the ANCA-AE embeddings depict a clear separation between the closed (darker purple) and open (yellow) conformations of the Delta spike. A sub-sampled landscape is shown here where each sphere represents a conformation from the WE simulations and colored with the root-mean squared deviations (Å) with respect to the closed state. Visualized with VMD. An external file that holds a picture, illustration, etc. Object name is 10.1177_10943420221128233-fig6.jpg Figure 6. WE simulations reveal a dramatic opening of the Delta S (cyan), compared to WT S (white). While further investigation is needed, this super open state seen in the Delta S may indicate increased capacity for binding to human host-cell receptors. The integration of AI techniques with WE can further enhance the efficiency of sampling rare events (Noe 2020; Brace et al., 2021b; Casalino et al., 2021). One frontier area couples unsupervised linear and non-linear dimensionality reduction methods to identify collective variables/progress coordinates in high-dimensional molecular systems (Bhowmik et al., 2018; Clyde et al., 2021). Such methods may be well suited for analyzing the aerosolized virus. Integrating these approaches with WE simulations is advantageous in sampling the closed ? open transitions in the Delta S landscape (Figure 5) as these unsupervised AI approaches automatically stratify progress coordinates (Figure 5(D)). Dynamical non-equilibrium MD Aerosols rapidly acidify during flight via reactive uptake of atmospheric gases, which is likely to impact the opening/closing of the S protein (Vejerano and Marr 2018; Warwicker 2021). Here, we describe the extension of dynamical non-equilibrium MD (D-NEMD) (Ciccotti and Ferrario 2016) to investigate pH effects on the Delta S. D-NEMD simulations (Ciccotti and Ferrario 2016) are emerging as a useful technique for identifying allosteric effects and communication pathways in proteins (Galdadas et al., 2021; Oliveira et al., 2019), including recently identifying effects of linoleic acid in the WT spike (Oliveira et al., 2021b). This approach complements equilibrium MD simulations, which provide a distribution of configurations as starting points for an ensemble of short non-equilibrium trajectories under the effect of the external perturbation. The response of the protein to the perturbation introduced can then be determined using the Kubo-Onsager relation (Oliveira et al., 2021a; Ciccotti and Ferrario 2016) by directly tracking the change in atomic positions between the equilibrium and non-equilibrium simulations at equivalent points in time (Oliveira et al., 2021a). OrbNet Ca2+ ions are known to play a key role in mucin aggregation in epithelial tissues (Hughes et al., 2019). Our RAV simulations would be an ideal case-study to probe such complex interactions between Ca2+, mucins, and the SARS-CoV-2 virion in aerosols. However, Ca2+ binding energies can be difficult to capture accurately due to electronic dispersion and polarization, terms which are not typically modeled in classical mechanical force fields. Quantum mechanical (QM) methods are uniquely suited to capture these subtle interactions. Thus, we set out to estimate the correlation in Ca2+ binding energies between CHARMM36m and quantum mechanical estimates enabled via AI with OrbNet. Calculation of energies with sufficient accuracy in biological systems can, in many cases, be adequately described with density functional theory (DFT). However, its high cost limits the applicability of DFT in comparison to fixed charge force fields. To capture quantum quality energetics at a fraction of the computational expense, we employ a novel approach (OrbNet) based on the featurization of molecules in terms of symmetry-adapted atomic orbitals and the use of graph neural network methods for deep learning quantum-mechanical properties (Qiao et al., 2020). Our method outperforms existing methods in terms of its training efficiency and transferable accuracy across diverse molecular systems, opening a new pathway for replacing DFT in large-scale scientific applications such as those explored here. (Christensen et al., 2021). Innovations realized Construction and simulation of SARS-CoV-2 in a respiratory aerosol Our approach to simulating the entire aerosol follows a composite framework wherein each of the individual molecular pieces is refined and simulated on its own before it is incorporated into the composite model. Simulations of each of the components are useful in their own right, and often serve as the basis for biochemical and biophysical validation and experiments (Casalino et al., 2020). Throughout, we refer to the original circulating SARS-CoV-2 strain as "WT," whereas all SARS-CoV-2 proteins constructed in this work represent the Delta variant (Figure 2). All simulated membranes reflect mammalian ER-Golgi intermediate compartment (ERGIC) mimetic lipid compositions. VMD (Humphrey et al., 1996; Stone et al., 2016a), psfgen (Phillips et al., 2005), and CHARMM-GUI (Park et al., 2019) were used for construction and parameterization. Topologies and parameters for simulations were taken from CHARMM36m all-atom additive force fields (Guvench et al., 2009; Huang and Mackerell 2013; Huang et al., 2017; Klauda et al., 2010; Beglov and Roux 1994; Han et al., 2018; Venable et al., 2013). NAMD was used to perform MD simulations (Phillips et al., 2020), adopting similar settings and protocols as in (Casalino et al., 2020). All systems underwent solvation, charge neutralization, minimization, heating, and equilibration prior to production runs. Refer to Table 1 for Abbreviations, PBC dimensions, total number of atoms, and total equilibration times for each system of interest. Table 1. Summary of all systems constructed in this work. See Figure 3 for illustration of aerosol construction. asystems bAbb c(Å × Å × Å) dNa e (ns) fM dimers M 125 × 125 × 124 164,741 700 fE pentamers E 123 × 125 × 102 136,775 41 Spikes f (Open) S 206 × 200 × 410 1,692,444 330 f (Closed) S 204 × 202 × 400 1,658,224 330 g (Closed, head) SH 172 × 184 × 206 615,593 73µs Mucins fshort mucin 1 m1 123 × 104 × 72 87,076 25 fshort mucin 2 m2 120 × 101 × 72 82,155 25 flong mucin 1 m3 810 × 104 × 115 931,778 23 flong mucin 2 m4 904 × 106 × 109 997,029 15 flong mucin 3 m5 860 × 111 × 113 1,040,215 18 fS+m1/m2+ALB SMA 227 × 229 × 433 2,156,689 840 fVirion V 1460 × 1460 × 1460 305,326,834 41 fResp.Aero.+Vir RAV 2834 × 2820 × 2828 1,016,813,441 2.42 Total FLOPS 2.4 ZFLOPS Open in a separate window aM, E, S, SH, and V models represent SARS-CoV-2 Delta strain. bAbbreviations used throughout document. cPeriodic boundary dimensions. dTotal number of atoms. eTotal aggregate simulation time, including heating and equilibration runs. fSimulated with NAMD. gSimulated with NAMD, AMBER, and GROMACS. Simulating the SARS-CoV-2 structural proteins Fully glycosylated Delta spike (S) structures in open and closed conformations were built based on WT constructs from Casalino et al. (Casalino et al., 2020) with the following mutations: T19R, T95I, G142D, E156G, ?157-158, L452R, T478K, D614G, P681R, and D950N (McCallum et al., 2021; Kannan et al., 2021). Higher resolved regions were grafted from PDB 7JJI (Bangaru et al., 2020). Additionally, coordinates of residues 128-167-accounting for a drastic conformational change seen in the Delta variant S-graciously made available to us by the Veesler Lab, were similarly grafted onto our constructs (McCallum et al., 2021). Finally, the S proteins were glycosylated following work by Casalino et al. (Casalino et al., 2020). By incorporating the Veesler Lab's bleeding-edge structure (McCallum et al., 2021) and highly resolved regions from 7JJI (Bangaru et al., 2020), our models represent the most complete and accurate structures of the Delta S to date. The S proteins were inserted into membrane patches and equilibrated for 3 × 110 ns. For non-equilibrium and weighted ensemble simulations, a closed S head (SH, residues 13-1140) was constructed by removing the stalk from the full-length closed S structure, then resolvated, neutralized, minimized, and subsequently passed to WE and D-NEMD teams. The M-protein was built from a structure graciously provided by the Feig Lab (paper in prep). The model was inserted into a membrane patch and equilibrated for 700 ns. RMSD-based clustering was used to select a stable starting M-protein conformation. From the equilibrated and clustered M structure, VMD's Mutator plugin (Humphrey et al., 1996) was used to incorporate the I82T mutation onto each M monomer to arrive at the Delta variant M. To construct the most complete E protein model to-date, the structure was patched together by resolving incomplete PDBs 5X29 (Surya et al., 2018), 7K3G (Mandala et al., 2020) and 7M4R (Chai et al., 2021). To do so, the transmembrane domain (residues 8-38) from 7K3G were aligned to the N-terminal domain (residues 1-7) and residues 39 to 68 of 5X29 and residues 69 to 75 of 7M4R by their Ca atoms. E was then inserted into a membrane patch and equilibrated for 40 ns. Constructing the SARS-CoV-2 Delta virion The SARS-CoV-2 Delta virion (V) model was constructed following Casalino et al. (Casalino et al., 2021) using CHARMM-GUI (Lee et al., 2016), LipidWrapper (Durrant and Amaro 2014), and Blender (Blender Online Community 2020), using a 350 Å lipid bilayer with an equilibrium area per lipid of 63 Å2 and a 100 nm diameter Blender icospherical surface mesh (Turonova et al., 2020). The resulting lipid membrane was solvated in a 1100 Å3 waterbox and subjected to four rounds of equilibration and patching (Casalino et al., 2021). 360 m dimers and 4 E pentamers were then tiled onto the surface, followed by random placement of 29 full-length S proteins (9 open, 20 closed) according to experimentally observed S protein density (Ke et al., 2020). M and E proteins were oriented with intravirion C-termini. After solvation in a 1460 Å waterbox, the complete V model tallied >305 million atoms (Table 1). V was equilibrated for 41 ns prior to placement in the respiratory aerosol (RA) model. The equilibrated membrane was 90 nm in diameter and remains in close structural agreement with the experimental studies (Ke et al., 2020). Building and simulating the respiratory aerosol Respiratory aerosols contain a complex mixture of chemical and biological species. We constructed a respiratory aerosol (RA) fluid based on a composition from artificial saliva and surrogate deep lung fluid recipes (Walker et al., 2021). This recipe includes 0.7 mm DPPG, 6.5 mm DPPC, 0.3 mm cholesterol, 1.4 mm Ca2+, 0.8 mm Mg2+, and 142 mm Na+ (Vejerano and Marr 2018; Walker et al., 2021), human serum albumin (ALB) protein, and a composition of mucins (Figure 3). Mucins are long polymer-like structures that are decorated by dense, heterogeneous, and complex regions of O-glycans. This work represents the first of its kind as, due to their complexity, the O-glycosylated regions of mucins have never before been constructed for molecular simulations. Two short (m1, m2, ~5 nm) and three long (m3, m4, m5 ~55 nm) mucin models were constructed following known experimental compositions of protein and glycosylation sequences (Symmes et al., 2018; Hughes et al., 2019; Markovetz et al., 2019; Thomsson et al., 2005; Mariethoz et al., 2018) with ROSETTA (Raveh et al., 2010) and CHARMM-GUI Glycan Modeller (Jo et al., 2011). Mucin models (short and long) were solvated, neutralized by charge matching with Ca2+ ions, minimized, and equilibrated for 15-25 ns each (Table 1). Human serum albumin (ALB), which is also found in respiratory aerosols, was constructed from PDB 1AO6 (Sugio et al., 1999). ALB was solvated, neutralized, minimized, and equilibrated for 7ns. Equilibrated structures of ALB and the three long mucins were used in construction of the RAV with m3+m4+m5 added at 6 g/mol and ALB at 4.4 g/mol. An external file that holds a picture, illustration, etc. Object name is 10.1177_10943420221128233-fig3.jpg Figure 3. Image of RAV with relative mass ratios of RA molecular components represented in the colorbar. Water content is dependent on the relative humidity of the environment and is thus omitted from the molecular ratios. Constructing the respiratory aerosolized virion model A 100 nm cubic box with the RA fluid recipe specified above was built with PACKMOL (Martínez et al., 2009), minimized, equilibrated briefly on TACC Frontera, then replicated to form a 300 nm cube. The RA box was then carved into a 270 nm diameter sphere. To make space for the placement of V within the RA, a spherical selection with volume corresponding to that of the V membrane + S crown (radius 734 Å) was deleted from the center of the RA. The final equilibrated V model, including surrounding equilibrated waters and ions (733 Å radius), was translated into the RA. Atom clashes were resolved using a 1.2 Å cutoff. Hydrogen mass repartitioning (Hopkins et al., 2015) was applied to the structure to improve performance. The simulation box was increased to 2800 Å per side to provide a 100 Å vacuum atmospheric buffer. The RAV simulation was conducted in an NVT ensemble with a 4 fs timestep. After minimizing, the RAV was heated to 298 K with 0.1 kcal/mol Å2 restraints on the viral lipid headgroups, then equilibrated for 1.5 ns. Finally, a cross-section of the RAV model-including and open S, m1/m2, and ALB (called the SMA system)-was constructed with PACKMOL to closely observe atomic scale interactions within the RAV model (Figure 4). An external file that holds a picture, illustration, etc. Object name is 10.1177_10943420221128233-fig4.jpg Figure 4. SMA system captured with multiscale modeling from classical MD to AI-enabled quantum mechanics. For all panels: S protein shown in cyan, S glycans in blue, m1/m2 shown in red, ALB in orange, Ca2+ in yellow spheres, viral membrane in purple. A) Interactions between mucins and S facilitated by glycans and Ca2+. B) Snapshot from SMA simulations. C) Example Ca2+ binding site from SMA simulations (1800 sites, each 1000+ atoms) used for AI-enabled quantum mechanical estimates from OrbNet Sky. D) Quantification of contacts between S and mucin from SMA simulations. E) OrbNet Sky energies versus CHARMM36m energies for each sub-selected system, colored by total number of atoms. Performance of OrbNet Sky versus DFT in subplot (?B97x-D3/def-TZVP, R2=0.99, for 17 systems of peptides chelating Ca2+ (Hu et al., 2021)). Visualized with VMD. Parameter evaluation with OrbNet Comparison to quantum methods reveals significant polarization effects, and shows that there is opportunity to improve the accuracy of fixed charge force fields. For the large system sizes associated with solvated Ca2+-protein interaction motifs (over 1000 atoms, even in aggressively truncated systems), conventional quantum mechanics methods like density functional theory (DFT) are impractical for analyzing a statistically significant ensemble of distinct configurations (see discussion in Performance Results). In contrast, OrbNet allows for DFT accuracy with over 1000-fold speedup, providing a useful method for benchmarking and refining the force field simulation parameters with quantum accuracy (Christensen et al., 2021). To confirm the accuracy of OrbNet versus DFT (?B97X-D/def2-TZVP), the inset of Figure 4(E) correlates the two methods for the Ca2+-binding energy in a benchmark dataset of small Ca2+-peptide complexes (Hu et al., 2021). The excellent correlation of OrbNet and DFT for the present use case is clear from the inset figure; six datapoints were removed from this plot on the basis of a diagnostic applied to the semi-empirical GFN-xTB solution used for feature generation of OrbNet (Christensen et al., 2021). Figure 4 presents a comparison of the validated OrbNet method with the CHARMM36m force field for 1800 snapshots taken from the SMA MD simulations. At each snapshot, a subsystem containing a solvated Ca2+-protein complex was extracted (Figure 4(E)), with protein bonds capped by hydrogens. For both OrbNet and the force field, the Ca2+-binding energy was computed and shown in the correlation plot. Lack of correlation between OrbNet and the force field identifies important polarization effects, absent in a fixed charge description. Similarly, the steep slope of the best-fit line in Figure 4(E) reflects the fact that some of the configurations sampled using MD with the CHARMM36m force field are relatively high in energy according to the more accurate OrbNet potential. This approach allows us to test and quantify limitations of empirical force fields, such as lack of electronic polarization. The practicality of OrbNet for these simulation snapshots with 1000+ atoms offers a straightforward multiscale strategy for refining the accuracy of the CHARMM36m force field. By optimizing the partial charges and other force field parameters, improved correlation with OrbNet for the subtle Ca2+-protein interactions could be achieved, leading to near-quantum accuracy simulations with improved configurational sampling. The calculations presented here present a proof-of-concept of this iterative strategy. AI-WE simulations of delta spike opening While our previous WE simulations of the WT SARS-CoV-2 S-opening (Sztain et al., 2021) were notable in generating pathways for a seconds-timescale process of a massive system, we have made two critical technological advancements in the WESTPA software that greatly enhance the efficiency and analysis of WE simulations. These advances enabled striking observations of Delta variant S opening (Figures 5 and and6).6). First, in contrast to prior manual bins for controlling trajectory replication, we have developed automated and adaptive binning that enables more efficient surmounting of large barriers via early identification of "bottleneck" regions (Torrillo et al., 2021). Second, we have parallelized, memory-optimized, and implemented data streaming for the history-augmented Markov state model (haMSM) analysis scheme (Copperman and Zuckerman 2020) to enable application to the TB-scale S-opening datasets. The haMSM approach estimates rate constants from simulations that have not yet reached a steady state (Suarez et al., 2014). Our WE simulations generated >800 atomically detailed, Delta variant S-opening pathways (Figures 5(B) and and6)6) of the receptor binding domain (RBD) switching from a glycan-shielded "down" to an exposed "up" state using 72 µs of total simulation time within 14 days using 192 NVIDIA V100 GPUs at a time on TACC's Longhorn supercomputer. Among these pathways, 83 reach an "open" state that aligns with the structure of the human ACE2-bound WT S protein (Benton et al., 2020) and 18 reach a dramatically open state (Figure 6). Our haMSM analysis of WT WE simulations successfully provided long-timescale (steady state) rate constants for S-opening based on highly transient information (Figure 5(C)). We also leveraged a simple, yet powerful unsupervised deep learning method called Anharmonic Conformational Analysis enabled Autoencoders (ANCA-AE) Clyde et al. (2021) to extract conformational states from our long-timescale WE simulations of Delta spike opening (Figures 5(A) and (D)). ANCA-AE first minimizes the fourth order correlations in atomistic fluctuations from MD simulation datasets and projects the data onto a low dimensional space where one can visualize the anharmonic conformational fluctuations. These projections are then input to an autoencoder that further minimizes non-linear correlations in the atomistic fluctuations to learn an embedding where conformations are automatically clustered based on their structural and energetic similarity. A visualization of the first three dimensions from the latent space articulates the RBD opening motion from its closed state (Figure 5(D)). It is notable that while other deep learning techniques need special purpose hardware (such as GPUs), the ANCA-AE approach can be run with relatively modest CPU resources and can therefore scale to much larger systems (e.g., the virion within aerosol) when optimized. D-NEMD explores pH effects on delta spike We performed D-NEMD simulations of the SH system with GROMACS (Abraham et al., 2015) using a ?pH=2.0 (from 7.0 to 5.0) as the external perturbation. We ran 3200-ns equilibrium MD simulations of SH to generate 87 configurations (29 configurations per replicate) that were used as the starting points for multiple short (10 ns) D-NEMD trajectories under the effect of the external perturbation (?pH=2.0). The effect of a ?pH was modeled by changing the protonation state of histidines 66, 69, 146, 245, 625, 655, 1064, 1083, 1088, and 1101 (we note that other residues may also become protonated (Lobo and Warwicker 2021); the D-NEMD approach can also be applied to examine those). The structural response of the S to the pH decrease was investigated by measuring the difference in the position for each Ca atom between the equilibrium and corresponding D-NEMD simulation at equivalent points in time (Oliveira et al., 2021a), namely after 0, 0.1, 1, 5, and 10 ns of simulation. The D-NEMD simulations reveal that pH changes, of the type expected in aerosols, affect the dynamics of functionally important regions of the spike, with potential implications for viral behavior (Figure 7). As this approach involves multiple short independent non-equilibrium trajectories, it is well suited for cloud computing. All D-NEMD simulations were performed using Oracle Cloud. An external file that holds a picture, illustration, etc. Object name is 10.1177_10943420221128233-fig7.jpg Figure 7. D-NEMD simulations reveal changes in key functional regions of the S protein, including the receptor binding domain, as the result of a pH decrease. Color scale and ribbon thickness indicate the degree of deviation of Ca atoms from their equilibrium position. Red spheres indicate the location of positively charged histidines. How performance was measured WESTPA For the WE simulations of spike opening using WESTPA, we defined the time-to-solution as the total simulation time required to generate the first spike opening event. Spike opening is essentially impossible to observe via conventional MD. WESTPA simulations were run using the AMBER20 dynamics engine and 192 NVIDIA V100 GPUs at a time on TACC's Longhorn supercomputer. NAMD NAMD performance metrics were collected using hardware performance counters for FLOPs/step measurements, and application-internal timers for overall simulation rates achieved by production runs including all I/O for simulation trajectory and checkpoint output. NAMD FLOPs/step measurements were conducted on TACC Frontera, by querying hardware performance counters with the rdmsr utility from Intel msr-tools1 and the "TACC stats" system programs.2 For each simulation, FLOP counts were measured for NAMD simulation runs of two different step counts. The results of the two simulation lengths were subtracted to eliminate NAMD startup operations, yielding an accurate estimate of the marginal FLOPs per step for a continuing simulation (Phillips et al., 2002). Using the FLOPs/step values computed for each simulation, overall FLOP rates were computed by dividing the FLOPs/step value by seconds/step performance data reported by NAMD internal application timers during production runs. GROMACS GROMACS 2020.4 benchmarking was performed on Oracle Cloud Infrastructure (OCI)3 compute shape BM.GPU4.8 consisting of 8×NVIDIA A100 tensor core GPUs, and 64 AMD Rome CPU cores. The simulation used for benchmarking contained 615,563 atoms and was run for 500,000 steps with 2 fs time steps. The simulations were run on increasing numbers of GPUs, from 1 to 8, using eight CPU cores per GPU, running for both the production (Nose-Hoover) and GPU-accelerated (velocity rescaling) thermostats. Particle-mesh Ewald (PME) calculations were pinned to a single GPU, with additional GPUs for multi-GPU jobs used for particle-particle calculations. Performance data (ns/day and average single-precision TFLOPS, calculated as total number of TFLOPs divided by total job walltime) were reported by GROMACS itself. Each simulation was repeated four times and average performance figures reported. Performance results Table 2. Table 2. MD simulation floating point ops per timestep. MD Simulation Code Atoms aFLOPs/step Spike, head AMBER, GROMACS 0.6 m 62.14 GFLOPs/step Spike NAMD 1.7 m 43.05 GFLOPs/step S+m1/m2+ALB NAMD 2.1 m 54.86 GFLOPs/step Resp. Aero.+Vir NAMD 1B 25.81 TFLOPs/step Open in a separate window aFLOPs/step data were computed by direct FLOP measurements from hardware performance counters for NAMD simulations, or by using the application-reported FLOP rates and ns/day simulation performance in the case of GROMACS. NAMD performance NAMD was used to perform all of the simulations listed in Table 1, except for the closed spike "SH" simulations described further below. With the exception of the aerosol and virion simulation, the other NAMD simulations used conventional protocols and have performance and parallel scaling characteristics that closely match the results reported in our previous SARS-CoV-2 research Casalino et al. (2021). NAMD 2.14 scaling performance for the one billion-atom respiratory aerosol and virion simulation run on ORNL Summit is summarized in Tables 3 and and4.4. A significant performance challenge associated with the aerosol virion simulation relates to the roughly 50% reduction in particle density as compared with a more conventional simulation with a fully populated periodic cell. The reduced particle density results in large regions of empty space that nevertheless incur additional overheads associated with both force calculations and integration, and creates problems for the standard NAMD load balancing scheme that estimates the work associated with the cubic "patches" used for parallel domain decomposition. The PME electrostatics algorithm and associated 3-D FFT and transpose operations encompass the entire simulation unit cell and associated patches, requiring involvement in communication and reduction operations despite the inclusion of empty space. Enabling NAMD diagnostic output on a 512-node 1B-atom aerosol and virion simulation revealed that ranks assigned empty regions of the periodic cell had 66 times the number of fixed-size patches as ranks assigned dense regions. The initial load estimate for an empty patch was changed from a fixed 10 atoms to a runtime parameter with a default of 40 atoms, which reduced the patch ratio from 66 to 19 and doubled performance on 512 nodes. Table 3. NAMD performance: Respiratory Aerosol + Virion, 1B atoms, 4 fs timestep w/HMR, and PME every three steps. Nodes Summit Speedup Efficiency CPU + GPU 256 4.18 ns/day ~1.0× ~100% 512 7.68 ns/day 1.84× 92% 1024 13.64 ns/day 3.27× 81% 2048 23.10 ns/day 5.53× 69% 4096 34.21 ns/day 8.19× 51% Open in a separate window Table 4. Peak NAMD FLOP rates, ORNL Summit. NAMD Simulation Atoms, B Nodes Sim rate Performance Resp. Aero.+Vir 1 4096 34.21 ns/day 2.55 PFLOPS Open in a separate window WESTPA performance Our time to solution for WE simulations of spike opening (to the "up" state) (Figure 5) using the WESTPA software and AMBER20 was 14 µs of total simulation time, which was completed in 4 days using 192 NVIDIA V100 GPUs at a time on TACC's Longhorn supercomputer. For reference, conventional MD would require an expected ~5 orders of magnitude more computing. The WESTPA software is highly scalable, with nearly perfect scaling out to >1000 NVIDIA V100 GPUs and this scaling is expected to continue until the filesystem is saturated. Thus, WESTPA makes optimal use of large supercomputers and is limited by filesystem I/O due to the periodic restarting of trajectories after short time intervals. AI-enhanced WE simulations DeepDriveMD is a framework to coordinate the concurrent execution of ensemble simulations and drive them using AI models Brace et al. (2021a); Lee et al. (2019). DeepDriveMD has been shown to improve the scientific performance of diverse problems: from-protein folding to conformation of protein-ligand complexes. We coupled WESTPA to DeepDriveMD, which is responsible for resource dynamism and concurrent heterogeneous task execution (ML and AMBER). The coupled workflow was executed on 1024 nodes on Summit (OLCF), and, in spite of the spatio-temporal heterogeneity of tasks involved, the resource utilization was in the high 90%. Consistent with earlier studies, the coupling of WESTPA to DeepDriveMD results in a 100x improvement in the exploration of phase space. GROMACS performance Figure 8 shows GROMACS parallelizes well across the eight NVIDIA A100 GPUs available on each BM.GPU4.8 instance used in the Cluster in the Cloud4 running on OCI. There is a performance drop for two GPUs due to inefficient division of the PME and particle-particle tasks. Methods to address this exist for the two GPU case Páll et al. (2020), but were not adopted as we were targeting maximum raw performance across all eight GPUs. Production simulations achieved 27% of the peak TFLOPS available from the GPUs. Multiple simulations were run across 10 such compute nodes, enabling the ensemble to run at an average combined speed of 425 TFLOPS and sampling up to 1µs/day. We note that the calculations will be able to run 20%-40% faster once the Nose-Hoover thermostat that is required for the simulation is ported to run on the GPU. Benchmarking using a velocity rescaling thermostat that has been ported to GPU shows that this would enable the simulation to extract 34% of the peak TFLOPS from the cards, enabling each node to achieve an average speed of 53.4 TFLOPS, and 125 ns/day. A cluster of 10 nodes would enable GROMACS to run at an average combined speed of over 0.5 PFLOPs, simulating over 1.2 µs/day. An external file that holds a picture, illustration, etc. Object name is 10.1177_10943420221128233-fig8.jpg Figure 8. GROMACS performance across 1-8 A100 GPUs in ns/day (thicker, blue lines) and the fraction of maximum theoretical TFLOPS (thinner, green lines); production setup shown with solid line, and runs with the GPU-accelerated thermostat in dashed. A significant innovation is that this power is available on demand: Cluster in the Cloud with GPU-optimized GROMACS was provisioned and benchmarked within 1 day of inception of the project. This was handed to the researcher, who submitted the simulations. Automatically, up to 10 BM.GPU4.8 compute nodes were provisioned on-demand based on requests from the Slurm scheduler. These simulations were performed on OCI, using Cluster in the Cloud Williams (2021) to manage automatic scaling. Cluster in the Cloud was configured to dynamically provision and terminate computing nodes based on the workload. Simulations were conducted using GROMACS 2020.4 compiled with CUDA support. Multiple simultaneous simulations were conducted, with each simulation utilizing a single BM.GPU4.8 node without multinode parallelism. This allowed all production simulations to be completed within 2 days. The actual compute cost of the project was less than $6125 USD (on-demand OCI list price). The huge reduction in "time to science" that low-cost cloud enables changes the way that researchers can access and use HPC facilities. In our opinion, such a setup enables "exclusive on-demand" HPC capabilities for the scientific community for rapid advancement in science. OrbNet performance Prior benchmarking reveals that OrbNet provides over 1000-fold speedup compared to DFT (Christensen et al., 2021). For the calculations presented here, the cost of corresponding high quality range-separated DFT calculations (?B97X-D/def2-TZVP) can be estimated. In Figure 4(E), we consider system sizes which would require 14,000-47,000 atomic orbitals for ?B97X-D/def2-TZVP, exceeding the range of typical DFT evaluations. Estimation of the DFT computational cost of the 1811 configurations studied in Figure 4(E) suggests a total of 115M core-hours on NERSC Cori Haswell nodes; in contrast, the OrbNet calculations for the current study require only 100k core-hours on the same nodes. DFT cost estimates were based on extrapolation from a dataset of over 1M ChEMBL molecules ranging in size from 40 to 107 atom systems considering only the cubic cost component of DFT (Christensen et al., 2021). Go to: Implications Our major scientific achievements are 1. We showcase an extensible AI-enabled multiscale computational framework that bridges time and length scales from electronic structure through whole aerosol particle morphology and dynamics. 2. We develop all-atom simulations of respiratory mucins, and use these to understand the structural basis of interaction with the SARS-CoV-2 spike protein. This has implications for viral binding in the deep lung, which is coated with mucins. We expect the impact of our mucin simulations to be far reaching, as malfunctions in mucin secretion and folding have been implicated in progression of severe diseases such as cancer and cystic fibrosis. 3. We present a significantly enhanced all-atom model and simulation of the SARS-CoV-2 Delta virion, which includes the hundreds of tiled M-protein dimers and the E-protein ion channels. This model can be used as a basis to understand why the Delta virus is so much more infectious than the WT or alpha variants. 4. We develop an ultra-large (1 billion+) all-atom simulation capturing massive chemical and biological complexity within a respiratory aerosol. This simulation provides the first atomic-level views of virus-laden aerosols and is already serving as a basis to develop an untold number of experimentally testable hypotheses. An immediate example suggests a mechanism through which mucins and other species, for example, lipids, which are present in the aerosol, arrange to protect the molecular structure of the virus, which otherwise would be exposed to the air-water interface. This work also opens the door for developing simulations of other aerosols, for example, sea spray aerosols, that are involved in regulating climate. 5. We evidence how changes in pH, which are expected in the aerosol environment, may alter dynamics and allosteric communication pathways in key functional regions of the Delta spike protein. 6. We characterize atomically detailed pathways for the spike-opening process of the Delta variant using WE simulations, revealing a dramatically open state that may facilitate binding to human host cells. 7. We demonstrate how parallelized haMSM analysis of WE data can provide physical rate estimates of spike opening, improving prior estimates by many orders of magnitude. The pipeline can readily be applied to the any variant spike protein or other complex systems of interest. 8. We show how HPC and cloud resources can be used to significantly drive down time-to-solution for major scientific efforts as well as connect researchers and greatly enable complex collaborative interactions. 9. We demonstrate how AI coupled to HPC at multiple levels can result in significantly improved effective performance, for example, with AI-driven WESTPA, and extend the reach and domain of applicability of tools ordinarily restricted to smaller, less complex systems, for example, with OrbNet. 10. While our work provides a successful use case, it also exposes weaknesses in the HPC ecosystem in terms of support for key steps in large/complex computational science campaigns. We find lack of widespread support for high performance remote visualization and interactive graphical sessions for system preparation, debugging, and analysis with diverse science tools to be a limiting factor in such efforts. Go to: Acknowledgements We thank Prof. Kim Prather for inspiring and informative discussions about aerosols and for her commitment to convey the airborne nature of SARS-CoV-2. We thank D. Veesler for sharing the Delta spike NTD coordinates in advance of publication. We thank B. Messer, D. Maxwell, and the Oak Ridge Leadership Computing Facility at Oak Ridge National Laboratory supported by the DOE under Contract DE-AC05-00OR22725. We thank the Texas Advanced Computing Center Frontera team, especially D. Stanzione and T. Cockerill, and for compute time made available through a Director's Discretionary Allocation (NSF OAC-1818253). We thank the Argonne Leadership Computing Facility supported by the DOE under DE-AC02-06CH11357. We thank the Pittsburgh Supercomputer Center for providing priority queues on Bridges-2 through the XSEDE allocation NSF TG-CHE060063. We thank N. Kern and J. Lee of the CHARMM-GUI support team for help converting topologies between NAMD and GROMACS. We thank J. Copperman, G. Simpson, D. Aristoff, and J. Leung for valuable discussions and support from NIH grant GM115805. NAMD and VMD are funded by NIH P41-GM104601. This work was supported by the NSF Center for Aerosol Impacts on Chemistry of the Environment (CAICE), National Science Foundation Center for Chemical Innovation (NSF CHE-1801971), as well as NIH GM132826, NSF RAPID MCB-2032054, an award from the RCSA Research Corp., a UC San Diego Moore's Cancer Center 2020 SARS-CoV-2 seed grant, to R.E.A. This work was also supported by Oracle Cloud credits and related resources provided by the Oracle for Research program. AJM and ASFO receive funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (PREDACTED Advanced Grant, Grant agreement No.: 101021207). Go to: Notes 1. https://github.com/intel/msr-tools 2. https://github.com/TACC/tacc_stats 3. https://www.oracle.com/cloud/ 4. https://cluster-in-the-cloud.readthedocs.io/ Go to: Footnotes The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by National Science Foundation (CHE- 1801971); National Science Foundation (MCB- 2032054); National Science Foundation (OAC-1818253); National Science Foundation (TG-CHE060063); U.S. Department of Energy (DE-AC02-06CH11357); U.S. Department of Energy (DE-AC05- 00OR22725); National Institutes of Health (P41-GM104601); National Institutes of Health (R01-GM132826). Go to: ORCID iDs Lorenzo Casalino https://orcid.org/0000-0003-3581-1148 Mia Rosenfeld https://orcid.org/0000-0002-8961-8231 Surl-Hee Ahn https://orcid.org/0000-0002-3422-805X John Russo https://orcid.org/0000-0002-2813-6554 Sofia Oliveira https://orcid.org/0000-0001-8753-4950 Clare Morris https://orcid.org/0000-0002-4314-5387 Alexander Brace https://orcid.org/0000-0001-9873-9177 Hyungro Lee https://orcid.org/0000-0002-4221-7094 Zhuoran Qiao https://orcid.org/0000-0002-5704-7331 Anima Anandkumar https://orcid.org/0000-0002-6974-6797 James Phillips https://orcid.org/0000-0002-2296-3591 John McCalpin https://orcid.org/0000-0002-2535-1355 Christopher Woods https://orcid.org/0000-0001-6563-9903 Matt Williams https://orcid.org/0000-0003-2198-1058 Richard Pitts https://orcid.org/0000-0002-2037-3360 Daniel Zuckerman https://orcid.org/0000-0001-7662-2031 Adrian Mulholland https://orcid.org/0000-0003-1015-4567 Arvind Ramanathan https://orcid.org/0000-0002-1622-5488 Lillian Chong https://orcid.org/0000-0002-0590-483X Rommie E Amaro https://orcid.org/0000-0002-9275-9553 Go to: References Abraham MJ, Murtola T, Schulz R, et al. 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| Title | New markers and new genotyping platform for wheat breeding |
| Description | New Axiom markers for use in wheat breeding |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | New markers and new GbyS genotyping platform for screening and genotyping wheat |
| Title | CCDC 1839028: Experimental Crystal Structure Determination |
| Description | Related Article: Agnieszka J. Szwalbe, Katherine Williams, Zhongshu Song, Kate de Mattos-Shipley, Jason L. Vincent, Andrew M. Bailey, Christine L. Willis, Russell J. Cox, Thomas J. Simpson|2019|Chemical Science|10|233|doi:10.1039/C8SC03778G |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc1zqnhv&sid=DataCite |
| Title | CCDC 1839029: Experimental Crystal Structure Determination |
| Description | Related Article: Agnieszka J. Szwalbe, Katherine Williams, Zhongshu Song, Kate de Mattos-Shipley, Jason L. Vincent, Andrew M. Bailey, Christine L. Willis, Russell J. Cox, Thomas J. Simpson|2019|Chemical Science|10|233|doi:10.1039/C8SC03778G |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc1zqnjw&sid=DataCite |
| Title | CerealsDB |
| Description | The CerealsDB web-site was created by members of the Functional Genomics Group at the University of Bristol. The site provides a range of facilities for the study of the wheat genome. The site has been designed with breeders in mind, and we hope that is will be easy and straightforward to use. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | There have been over 1,528,817 unique visits to the websites and our various datasets have been downloaded 48,295 times (35K Wheat breeders Array: 45,445 downloads and 820K High Density Wheat Array; 2,850 downloads). The trend of increased numbers of researchers visiting our web site shows no sign of slowing down; running as it is at greater than 50,000 unique visits per month. |
| URL | http://www.cerealsdb.uk.net/ |
| Title | Chemical Shift Files for mupirocin mAcpD |
| Description | BMRB code 34451: NMR chemical shifts associated with PDB code 6TG5 and deposited in BioMagResBank |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | This work contributed to a recent publication (ACS Chem. Biol. 2020, https://doi.org/10.1021/acschembio.9b00969, A Priming Cassette Generates Hydroxylated Acyl Starter Units in Mupirocin and Thiomarinol Biosynthesis). Understanding starter unit selection has widespread application in bioengineering, synthetic biology and natural product research for increasing the chemical diversity of engineered high-value compounds of commercial and therapeutic value. |
| URL | http://www.bmrb.wisc.edu |
| Title | Data associated with the publication "Assembling membraneless organelles from de novo designed proteins" |
| Description | Raw data used in the manuscript "Assembling membraneless organelles from de novo designed proteins" |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | Supporting data for publication |
| URL | https://zenodo.org/record/7878607 |
| Title | Data from Understanding metabolic behaviour whole-cell model |
| Description | We provide tools to analyse single gene knock-out simulations of the Mycoplasma Genitalium whole-cell model. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| URL | https://data.bris.ac.uk/data/dataset/3u1v7dy42fk332watjl81m13y0/ |
| Title | Engineering protein stability with atomic precision in a monomeric miniprotein |
| Description | |
| Type Of Material | Database/Collection of data |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| URL | https://bmrb.io/data_library/summary/?bmrbId=34033 |
| Title | Engineering protein stability with atomic precision in a monomeric miniprotein |
| Description | |
| Type Of Material | Database/Collection of data |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| URL | https://bmrb.io/data_library/summary/?bmrbId=34032 |
| Title | Engineering protein stability with atomic precision in a monomeric miniprotein |
| Description | |
| Type Of Material | Database/Collection of data |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| URL | https://bmrb.io/data_library/summary/?bmrbId=34031 |
| Title | High Efficiency Excitation Energy Transfer in Biohybrid Quantum Dot-Bacterial Reaction Center Nanoconjugates |
| Description | Transient absorption, linear absorption and fluorescence, time resolved fluorescence data underpinning published paper. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://data.bris.ac.uk/data/dataset/3hqsgdntr1g842l47xrke8duj0/ |
| Title | Minimal Genome Design Algorithms using whole-cell models Rees-Garbutt and Chalkley et al 2019 |
| Description | In the future, entire genomes tailored to specific functions and environments could be designed using computational tools. However, computational tools for genome design are currently scarce. Here we present algorithms that enable the use of design-simulate-test cycles for genome design, using genome minimisation as a proof-of-concept. Minimal genomes are ideal for this purpose as they have a simple functional assay whether the cell replicates or not. We used the first (and currently only published) whole-cell model for the bacterium Mycoplasma genitalium. Our computational design-simulate-test cycles discovered novel in-silico minimal genomes which, if biologically correct, predict in-vivo genomes smaller than JCVI-Syn3.0; a bacterium with, currently, the smallest genome that can be grown in pure culture. In the process, we identified 10 low essential genes and produced evidence for at least two Mycoplasma genitalium in-silico minimal genomes. This work brings combined computational and laboratory genome engineering a step closer. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| URL | https://data.bris.ac.uk/data/dataset/1jj0fszzrx9qf2ldcz654qp454/ |
| Title | NMR structure of repeat domain 13 of the fibrillar adhesin CshA from Streptococcus gordonii. |
| Description | |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| URL | https://bmrb.io/data_library/summary/?bmrbId=34439 |
| Title | Protein PDB coordinates for MupZ |
| Description | PDB code 6FXD: Crystal structure coordinates of MupZ from the mupirocin biosynthetic gene cluster from Pseudomonas Fluoroscens. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | The discovery that MupZ can direct an anti-Baldwin ring closure, and is promiscuous, has led to further investigations into its application as a biocatalyst. This relates to follow on funding studying Diels-Alderase enzymes and work with Industrial Partners AstraZeneca who have invested over £100K to begin to develop the application of these enzymes further in industrial processes. |
| URL | https://www.rcsb.org |
| Title | Solution structure of MacpD, a acyl carrier protein, from Pseudomonas fluorescens involved in Mupirocin biosynthesis. |
| Description | |
| Type Of Material | Database/Collection of data |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| URL | https://bmrb.io/data_library/summary/?bmrbId=34451 |
| Title | Upgrade to cerealsdb (cerealsdb3) |
| Description | We have carried out a significant upgrade of cerealsdb to include new analytical tools and a much larger data set |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| Impact | Increased level of data downloads and use of tools to detect introgressions in wheat |
| URL | http://www.cerealsdb.uk.net/cerealgenomics/CerealsDB/indexNEW.php |
| Description | Biomolecular simulation for TB drug lead discovery |
| Organisation | Ubon Ratchathani University |
| Country | Thailand |
| Sector | Academic/University |
| PI Contribution | The enoyl-acyl carrier protein reductase InhA of Mycobacterium tuberculosis is an attractive, validated target for antituberculosis drug development. Moreover, direct inhibitors of InhA remain effective against InhA variants with mutations associated with isoniazid resistance, offering the potential for activity against MDR isolates. Here, structure-based virtual screening supported by biological assays was applied to identify novel InhA inhibitors as potential antituberculosis agents. High-speed Glide SP docking was initially performed against two conformations of InhA differing in the orientation of the active site Tyr158. The resulting hits were filtered for drug-likeness based on Lipinski's rule and avoidance of PAINS-like properties and finally subjected to Glide XP docking to improve accuracy. Sixteen compounds were identified and selected for in vitro biological assays, of which two (compounds 1 and 7) showed MIC of 12.5 and 25 µg/mL against M. tuberculosis H37Rv, respectively. Inhibition assays against purified recombinant InhA determined IC50 values for these compounds of 0.38 and 0.22 µM, respectively. A crystal structure of the most potent compound, compound 7, bound to InhA revealed the inhibitor to occupy a hydrophobic pocket implicated in binding the aliphatic portions of InhA substrates but distant from the NADH cofactor, i.e., in a site distinct from those occupied by the great majority of known InhA inhibitors. This compound provides an attractive starting template for ligand optimization aimed at discovery of new and effective compounds against M. tuberculosis that act by targeting InhA. |
| Collaborator Contribution | Discovery of new and potent InhA inhibitors as antituberculosis agents: Structure-based virtual screening validated by biological assays and X-ray crystallography. Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) remains a major worldwide public health problem, especially in areas of high population density and low- and middle-income countries. It is the leading cause of death by infectious disease and the ninth leading overall cause of death worldwide. World Health Organization (WHO) data identified 1.6 million TB deaths and 10 million new TB cases in 2017. (1) Although TB is considered treatable, this is threatened by the spread of drug-resistant strains; it is estimated that globally there are 4.9 million cases of patients infected with multidrug-resistant tuberculosis (MDR-TB) strains resistant to isoniazid and rifampicin, the two most important anti-TB agents. In 2017, 558 000 new cases of TB were identified that were resistant to rifampicin (RR-TB), the most effective first-line drug, with 82% of these MDR-TB. About 8% of TB patients worldwide are estimated to be infected with rifampicin-susceptible, isoniazid-resistant strains (HR-TB). (2) The M. tuberculosis enoyl-acyl carrier protein (ACP) reductase (M. tuberculosis InhA) is an attractive potential target for development of new antituberculosis drugs. InhA catalyzes the NADH-specific reduction of 2-trans-enoyl-ACP (Figure 1A) in the elongation cycle of the fatty acid synthase type II (FAS II) pathway, the final step of fatty acid biosynthesis in M. tuberculosis. (3,4) InhA is the primary target of isoniazid (INH), the second first-line drug for tuberculosis treatment. (5-7) However, the inhibitory activity of isoniazid is reduced by mutations either in InhA or, more commonly, in the KatG catalase-peroxidase responsible for converting the INH prodrug into its active form. (8-10) Thus, identifying inhibitors that directly bind to InhA without the requirement for activation by KatG (direct InhA inhibitors) may represent a valid strategy to overcome isoniazid resistance. (11,12) Hence multiple academic and pharmaceutical efforts have led to the discovery of direct InhA inhibitors. (13-18) However, most of the direct InhA inhibitors so far identified display good InhA inhibitory activity in vitro but poor activity against M. tuberculosis. (13,19-21) Figure 1 Figure 1. NADH-specific reduction of 2-trans-enoyl-ACP catalyzed by InhA (A), in and out conformations of Tyr158 side chain (B). Tyr158 in the in conformation (yellow) in the ternary InhA structure complexed with the C16 substrate analogue THT (trans-2-hexadecenoyl-(N-acetylcysteamine)-thioester (yellow carbon atom) and NAD+ (gray) and Tyr158 in the out conformation (pink) in the binary InhA structure complexed with NAD+ (gray). PDB codes of these structures are 1BVR (3) and 1ENY, (6) respectively. The interactions of InhA with substrate, cofactor, and inhibitors have been extensively studied. (22) One outcome of these investigations is the identification of the active site residue Tyr158 as important both to stabilizing the substrate during the catalytic reaction of M. tuberculosis InhA and to the binding of direct InhA inhibitors. (3,4,23) Two different conformations of the Tyr158 side chain have been identified in binding of direct InhA inhibitors (Figure 1B), an "in" conformation associated with the ternary InhA complex (substrate/cofactor-bound form) and an "out" conformation resembling that observed in the binary InhA complex (cofactor-bound form). (19-24) In the present work, we have applied structure-based virtual screening to select candidate InhA inhibitors from the compound library of the Specs database (www.specs.net), seeking to account for the mobility of Tyr158 by including both conformations of this residue in the screening workflow. This protocol identified two compounds that showed both inhibitory activity against M. tuberculosis cell growth and submicromolar inhibition of purified InhA in in vitro activity assays. A crystal structure for the complex of the most potent of these with InhA identified inhibitor binding in a hydrophobic active site pocket utilized in substrate binding and with Tyr158 in the in conformation. These findings demonstrate that these approaches can identify compounds with InhA inhibitory activity that are active against M. tuberculosis. Further experiments and simulations in progress. |
| Impact | Training in interactive virtual reality, molecular modelling, simulation and structural biology. Exchange visits. Biological assays. Publications: 1: Pakamwong B, Thongdee P, Kamsri B, Phusi N, Taveepanich S, Chayajarus K, Kamsri P, Punkvang A, Hannongbua S, Sangswan J, Suttisintong K, Sureram S, Kittakoop P, Hongmanee P, Santanirand P, Leanpolchareanchai J, Spencer J, Mulholland AJ, Pungpo P. Ligand-Based Virtual Screening for Discovery of Indole Derivatives as Potent DNA Gyrase ATPase Inhibitors Active against Mycobacterium tuberculosis and Hit Validation by Biological Assays. J Chem Inf Model. 2024 Aug 12;64(15):5991-6002. doi: 10.1021/acs.jcim.4c00511. Epub 2024 Jul 12. PMID: 38993154; PMCID: PMC11323271. 2: Kamsri B, Kamsri P, Punkvang A, Chimprasit A, Saparpakorn P, Hannongbua S, Spencer J, Oliveira ASF, Mulholland AJ, Pungpo P. Signal Propagation in the ATPase Domain of Mycobacterium tuberculosis DNA Gyrase from Dynamical- Nonequilibrium Molecular Dynamics Simulations. Biochemistry. 2024 Jun 4;63(11):1493-1504. doi: 10.1021/acs.biochem.4c00161. Epub 2024 May 14. PMID: 38742407; PMCID: PMC11154950. 3: Kamsri B, Pakamwong B, Thongdee P, Phusi N, Kamsri P, Punkvang A, Ketrat S, Saparpakorn P, Hannongbua S, Sangswan J, Suttisintong K, Sureram S, Kittakoop P, Hongmanee P, Santanirand P, Leanpolchareanchai J, Goudar KE, Spencer J, Mulholland AJ, Pungpo P. Bioisosteric Design Identifies Inhibitors of Mycobacterium tuberculosis DNA Gyrase ATPase Activity. J Chem Inf Model. 2023 May 8;63(9):2707-2718. doi: 10.1021/acs.jcim.2c01376. Epub 2023 Apr 19. PMID: 37074047. 4: Thongdee P, Hanwarinroj C, Pakamwong B, Kamsri P, Punkvang A, Leanpolchareanchai J, Ketrat S, Saparpakorn P, Hannongbua S, Ariyachaokun K, Suttisintong K, Sureram S, Kittakoop P, Hongmanee P, Santanirand P, Mukamolova GV, Blood RA, Takebayashi Y, Spencer J, Mulholland AJ, Pungpo P. Virtual Screening Identifies Novel and Potent Inhibitors of Mycobacterium tuberculosis PknB with Antibacterial Activity. J Chem Inf Model. 2022 Dec 26;62(24):6508-6518. doi: 10.1021/acs.jcim.2c00531. Epub 2022 Aug 22. PMID: 35994014. 5: Hanwarinroj C, Thongdee P, Sukchit D, Taveepanich S, Kamsri P, Punkvang A, Ketrat S, Saparpakorn P, Hannongbua S, Suttisintong K, Kittakoop P, Spencer J, Mulholland AJ, Pungpo P. In silico design of novel quinazoline-based compounds as potential Mycobacterium tuberculosis PknB inhibitors through 2D and 3D-QSAR, molecular dynamics simulations combined with pharmacokinetic predictions. J Mol Graph Model. 2022 Sep;115:108231. doi: 10.1016/j.jmgm.2022.108231. Epub 2022 May 28. PMID: 35667143. 6: Hanwarinroj C, Phusi N, Kamsri B, Kamsri P, Punkvang A, Ketrat S, Saparpakorn P, Hannongbua S, Suttisintong K, Kittakoop P, Spencer J, Mulholland AJ, Pungpo P. Discovery of novel and potent InhA inhibitors by an in silico screening and pharmacokinetic prediction. Future Med Chem. 2022 May;14(10):717-729. doi: 10.4155/fmc-2021-0348. Epub 2022 Apr 29. PMID: 35485258. 7: Pakamwong B, Thongdee P, Kamsri B, Phusi N, Kamsri P, Punkvang A, Ketrat S, Saparpakorn P, Hannongbua S, Ariyachaokun K, Suttisintong K, Sureram S, Kittakoop P, Hongmanee P, Santanirand P, Spencer J, Mulholland AJ, Pungpo P. Identification of Potent DNA Gyrase Inhibitors Active against Mycobacterium tuberculosis. J Chem Inf Model. 2022 Apr 11;62(7):1680-1690. doi: 10.1021/acs.jcim.1c01390. Epub 2022 Mar 29. PMID: 35347987. 8: Kamsri P, Hanwarinroj C, Phusi N, Pornprom T, Chayajarus K, Punkvang A, Suttipanta N, Srimanote P, Suttisintong K, Songsiriritthigul C, Saparpakorn P, Hannongbua S, Rattanabunyong S, Seetaha S, Choowongkomon K, Sureram S, Kittakoop P, Hongmanee P, Santanirand P, Chen Z, Zhu W, Blood RA, Takebayashi Y, Hinchliffe P, Mulholland AJ, Spencer J, Pungpo P. Discovery of New and Potent InhA Inhibitors as Antituberculosis Agents: Structure-Based Virtual Screening Validated by Biological Assays and X-ray Crystallography. J Chem Inf Model. 2020 Jan 27;60(1):226-234. doi: 10.1021/acs.jcim.9b00918. Epub 2019 Dec 27. PMID: 31820972. 9: Kamsri P, Punkvang A, Hannongbua S, Suttisintong K, Kittakoop P, Spencer J, Mulholland AJ, Pungpo P. In silico study directed towards identification of the key structural features of GyrB inhibitors targeting MTB DNA gyrase: HQSAR, CoMSIA and molecular dynamics simulations. SAR QSAR Environ Res. 2019 Nov;30(11):775-800. doi: 10.1080/1062936X.2019.1658218. PMID: 31607177. 10: Punkvang A, Kamsri P, Mulholland A, Spencer J, Hannongbua S, Pungpo P. Simulations of Shikimate Dehydrogenase from Mycobacterium tuberculosis in Complex with 3-Dehydroshikimate and NADPH Suggest Strategies for MtbSDH Inhibition. J Chem Inf Model. 2019 Apr 22;59(4):1422-1433. doi: 10.1021/acs.jcim.8b00834. Epub 2019 Mar 14. PMID: 30840825. |
| Start Year | 2015 |
| Description | BrisSynBio - Bruker |
| Organisation | Bruker Corporation |
| Country | United States |
| Sector | Private |
| PI Contribution | Expected contribution will include access to the BrisSynBio 700MHz Nuclear Magnetic Resonance spectrometer fitted 1.7mm cryogenically coiled RF probe optimised for ultra low sample volumes. |
| Collaborator Contribution | Cash contribution of £80,000 in exchange for obsolete NMR equipment and for access to the BrisSynBio NMR instrument In kind contribution of 10 days per year for five years enabling access to Bruker NMR specialist scientists and factory development groups. |
| Impact | None yet |
| Start Year | 2014 |
| Description | BrisSynBio - GSK |
| Organisation | GlaxoSmithKline (GSK) |
| Country | Global |
| Sector | Private |
| PI Contribution | Expected contribution is academic discovery and intellectual input in the field of pharmaceutics. |
| Collaborator Contribution | Access to in house screening for anti-microbials via the GSK Open Lab facility in Tres Cantos GSK will have board position on the BrisSynBio Scientific Advisory Board |
| Impact | None yet. |
| Start Year | 2014 |
| Description | BrisSynBio - IEU |
| Organisation | University of Bristol |
| Department | MRC Integrative Epidemiology Unit |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Expected contribution is academic collaboration and intellectual input in the field of Nuclear Magnetic Resonsnce technology and technology development. The IEU have a high-throughput NMR instrument for metabolomic studies which will be located adjacent to the BrisSynBio NMR instrument. Access to the BrisSynBio NMR instrument. |
| Collaborator Contribution | Cash contribution of £7500 towards the purchase of the BrisSynBio NMR instrument. |
| Impact | None yet. |
| Start Year | 2014 |
| Description | BrisSynBio - Syngenta |
| Organisation | Syngenta International AG |
| Country | Switzerland |
| Sector | Private |
| PI Contribution | Expected contribution is academic discovery and intellectual input in the field of agri-chemicals. |
| Collaborator Contribution | Input into BrisSynBio via contribution to the Scientific Advisory Board and attendance at other BrisSynBio scientific meetings (4 staff days per year for five years) Access to platform of in vitro and whole organism screens for novel compounds via the Centre for Agrochemical Activity Hosting of student and researcher visits Access to conference facilities for a joint BrisSynBio - Syngenta meeting |
| Impact | None yet |
| Start Year | 2014 |
| Description | BrisSynBio - UCB Celltech |
| Organisation | UCB Pharma |
| Department | UCB Celltech |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Expected contribution includes academic discovery and intellectual input to the development of innovate technologies to positively impact on the progression of UCB drug discovery projects. Access to the BrisSynBio NMR instrument. |
| Collaborator Contribution | Cash contribution of £100,000 towards the purchase of a 700MHz Nuclear Magnetic resonance spectrometer equipped with a 1.7mm cryogenically coiled RF probe optimised for ultra low sample volumes. |
| Impact | None yet. |
| Start Year | 2014 |
| Description | Collaboartion with Syngenta to exchnage knowledge on trasformation and double haploid production |
| Organisation | Syngenta International AG |
| Department | Syngenta Ltd (Bracknell) |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | exchange of personal to improve our technology in double haploid production |
| Collaborator Contribution | Spent time at Syngenta providing input into transformation technolgy |
| Impact | Better transformation and double haploid technology available to Bristol |
| Start Year | 2019 |
| Description | Max Planck Bristol Centre for Minimal Biology |
| Organisation | Max Planck Society |
| Country | Germany |
| Sector | Charity/Non Profit |
| PI Contribution | The Max Planck Bristol Centre (MPBC) for Minimal Biology is to be a joint initiative of the Max Planck Society for the Advancement of Science (MPG) and the University of Bristol, UK. The initiative is initially for 5 years, to be extended following an evaluation by a further 5 years to complete the full Centre lifetime (10 years). The proposal arises from emerging interactions and collaborations between the groups of Spatz (MPI for Medical Research, Heidelberg), Schwille (MPI for Biochemistry, München), Weil (MPI for Polymer Research, Mainz) and Berger (Department School of Biochemistry, Bristol), Mann (School of Chemistry, Bristol) and Woolfson (Bristol BioDdesign Institute) in the new interdisciplinary field of minimal biology that embraces state-of-the-art discoveries in chemistry, biology and microscale engineering. Together, we will pioneer an unprecedented approach that seeks to discover, understand and formalize three key frontier areas: synthetic cellularity/protobiology; crafting synthetic cytoskeletons de novo; and synthetic nanoscale biology. |
| Collaborator Contribution | As above |
| Impact | None yet |
| Start Year | 2019 |
| Description | Oracle for Research |
| Organisation | Oracle Corporation |
| Department | Oracle Corporation UK Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | We provide high value research problems with advanced cloud comuting requirements |
| Collaborator Contribution | Oracle for Research provide cloud computing infrastructure |
| Impact | 'Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2' by K Gupta et al in Nature Communications 'Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein' by O Staufer et al in Nature Communications 'Free fatty acid binding pocket in the locked structure of SARS CoV-2 spike protein' by C Toelzer et al in Science. |
| Start Year | 2019 |
| Description | Reconstitution of peptidoglycan transport through AmpG with Dr Patrick Moynihan |
| Organisation | University of Birmingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | WE are reconstituting nano reactors for reconstitution and monitoring the transport of peptidoglycan through the transporter AmpG |
| Collaborator Contribution | Provision of expertise and substrates fro transport (native and derivatives) |
| Impact | Not yet |
| Start Year | 2016 |
| Description | The Bacterial Sec Machinery with Dr Andrew Woodland |
| Organisation | University of Dundee |
| Department | Drug Discovery Unit |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Provision of samples and expertise for measurement of ATP driven protein transport through the bacterial Sec machinery |
| Collaborator Contribution | Expertise for high-throughput analysis and exposure to large small chemical libraries to search fro potent inhibitors (potential anti-bacterial) |
| Impact | Work in progress |
| Start Year | 2012 |
| Description | Wellcome Trust Centre for Mitochondrial Research Newcastle UK |
| Organisation | Newcastle University |
| Department | Mitochondrial Research Group |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Upon discovery of mitochondrial editing tools we will collaborate with the Newcastle group to use in primary cells. |
| Collaborator Contribution | Supply/availability of primary cells |
| Impact | None as yet |
| Start Year | 2016 |
| Title | Confidential |
| Description | Confidential |
| IP Reference | Confidential |
| Protection | Patent / Patent application |
| Year Protection Granted | 2024 |
| Licensed | Commercial In Confidence |
| Impact | Confidential |
| Title | BSim 2.0 (di Bernardo) |
| Description | BSim is an agent-based modelling tool designed to allow for the study of bacterial populations. |
| Type Of Technology | Software |
| Year Produced | 2016 |
| Open Source License? | Yes |
| Impact | Not yet evaluated. |
| URL | https://pubs.acs.org/doi/abs/10.1021/acssynbio.7b00121 |
| Title | BrisSynBio equipment calendar (Woods) |
| Description | A webtool for managing lab equipment bookings. Used by BrisSynBio. |
| Type Of Technology | Software |
| Year Produced | 2014 |
| Impact | This has been rolled out to other groups at University of Bristol where it has streamlined booking processes and enabled collection and analysis of booking and usage data. |
| Title | DNAplotlib (Gorochowski) |
| Description | DNAplotlib is a library that enables highly customizable visualization of individual genetic constructs and libraries of design variants. The tool's online code repository is shared by over 131 developers from across the world and it has been integrated into cutting-edge genetic software such as Cello. |
| Type Of Technology | Software |
| Year Produced | 2015 |
| Open Source License? | Yes |
| Impact | Not yet evaluated. |
| URL | https://pubs.acs.org/doi/abs/10.1021/acssynbio.6b00252 |
| Title | Elfin (Parmeggiani) |
| Description | Elfin is a software for the rapid design of proteins with custom shapes using experimentally validated protein building blocks. |
| Type Of Technology | Software |
| Year Produced | 2017 |
| Open Source License? | Yes |
| Impact | Not yet evaluated. |
| URL | https://www.sciencedirect.com/science/article/pii/S1047847717301417?via%3Dihub |
| Title | ISAMBARD |
| Description | Builds parametric models of proteins for protein design. |
| Type Of Technology | Software |
| Year Produced | 2017 |
| Open Source License? | Yes |
| Impact | Becoming widely used by protein designers and engineers. |
| URL | http://woolfson-group.github.io/index.html |
| Company Name | CDotBio |
| Description | CDotBio operates a biotechnology company which screens and develops desired genetic traits for crops. |
| Year Established | 2021 |
| Impact | None yet |
| Website | http://cdotbio.co.uk |
| Company Name | Glaia |
| Description | Glaia develops biostimulants for the agricultural sector, aiming to increase crop yield, without increasing greenhouse gases, by enhancing the rate of photosynthesis. |
| Year Established | 2019 |
| Impact | None yet |
| Website | http://glaia.co.uk |
| Company Name | Halo Therapeutics |
| Description | Halo Therapeutics develops antivirals to treat a range of Coronavirus diseases. |
| Year Established | 2020 |
| Impact | None yet |
| Website | http://halo-therapeutics.com |
| Company Name | Hone Bio |
| Description | Hone Bio develops cell membrane augmentation technology, with applications in cell therapies for various disorders. |
| Year Established | 2017 |
| Impact | Not yet evaluated. |
| Website | http://sciencecreates.co.uk |
| Company Name | Imophoron |
| Description | Imophoron develops a range of therapeutics. |
| Year Established | 2017 |
| Impact | Not yet evaluated. |
| Website | http://imophoron.com |
| Company Name | Rosa Biotech |
| Description | Rosa Biotech develops artificially intelligent biosensing tools based on nano-scale peptide barrels, with applications in industrial research and clinical diagnostics. |
| Year Established | 2019 |
| Impact | NA |
| Website | http://www.rosabio.tech |
| Company Name | Scarlet Therapeutics |
| Description | Scarlet Therapeutics develops engineered red blood cell-based therapeutics for a range of disease applications. |
| Year Established | 2021 |
| Impact | None yet |
| Website | http://scarlet-tx.com |
| Company Name | Zentraxa |
| Description | Zentraxa operates a synthetic biology platform that designs, produces and tests novel peptides, which can then be used to treat human diseases. |
| Year Established | 2017 |
| Impact | Not yet evaluated. |
| Website | http://zentraxa.com |
| Description | 'Dynamic Cell' Interactive Experience (Einsteins Garden, Green Man Music Festival, August 2017) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Dynamic Cell was an immersive experience exploring complex cellular processes. The project was a collaboration between University of Bristol scientists, a puppet-maker and performers. It was produced by Einstein's Garden for Green Man Festival, 2016. In the festival programme Dynamic Cell was described as follows: Experience the alien world of a cell: a weird, constantly transforming landscape of fascinating complex processes on a microscopic scale. Journey through this bizarre environment then join cell biologists to uncover the secrets of life by measuring, modelling and manipulating the cell. During the 3-day festival, the Dynamic Cell experience was open for approximately 6 hours each day. Visitors to the cell were invited to enter the cell with a small group to experience the complexity of the cellular environment, illustrated by a short puppet show. Particular themes in represented in the cell included: the central dogma (DNA-RNA-protein, transcription, translation etc.); protein folding; the DNA damage response; genome editing. In particular, one element of Dynamic Cell was an interactive set of 'CRISPR gloves' which were a talking point around which conversations about genome engineering, and in some cases mitochondrial genome engineering, took place. Dynamic Cell will be redelivered in the South West in the summer of 2017. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://einsteinsgarden.net/portfolio/dynamic-cell/ |
| Description | 6th form symposium King's College Taunton: Do Scientists dream of Synthetic sheep? (Heal) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | In collaboration with colleagues from other two other local independent schools in Taunton, King's College hosted a chemistry symposium for lower 6th pupils. Dr Jack Heal performed his stand up comedy show "Do Scientists dream of Synthetic sheep?", alongide other invited speakers. Purpose: To get the Chemists of the future enthused about science. |
| Year(s) Of Engagement Activity | 2016 |
| Description | ADDomer Media Campaign |
| 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 | Media (as a channel to the public) |
| Results and Impact | Comprehensive media campaign to raise awareness of the ADDomer vaccine platform technology. The social media campaign went viral, and the story has continued to propagate though the media and beyond. This has resulted in new collaborations and partnerships. We expect to see clinical impact from the underpinning research in due course. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.bbc.co.uk/news/business-49974477 |
| Description | Altering Plants, Microbes and People Panel event at the Watershed in Bristol |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | I was one of five expert panel members at this event, which we ran twice: once for professional synthetic biologists from the South West region (GW4 alliance of universities - Exeter, Bath, Bristol and Cardiff) and again for the general public in Bristol. Each time 50-100 people attended. The audience were clearly highly engaged in the discussions at both events. |
| Year(s) Of Engagement Activity | 2015,2016 |
| URL | http://www.bristol.ac.uk/engineering/events/2016/plants-microbes-people.html |
| Description | BBC Documentary (Paul Race) |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | The Truth about Antibiotics: A BBC documentary exploring ways that scientists are trying to fight bacterial infections, as they try to combat antibiotic resistance. Wild alligators and a sewage works are just two of the places Angela Rippon discovers that scientists are looking for new ways to fight bacterial infections. Angela reveals how a growing number of bacterial diseases are becoming resistant to the antibiotics currently in use. If nothing is done, millions could die. Angela Rippon investigated the latest scientific breakthroughs, meets a GP on the front line in the fight against infection and finds out how we can all take part in the effort to keep the miracle cure effective. Less |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.bbc.co.uk/iplayer/episode/b0c1nl68/the-truth-about-19-antibiotics |
| Description | BBC Newsnight: Coronavirus Research |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | BBC Newsnight focus on research being undertaken in the Bristol BioDesign Institute to tackle the 2019/2020 COVID-19 epidemic. The piece showcased the BrisSynBio founded BioSuite facility which includes robotic liquid handling platforms for protein production and purification. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.bbc.co.uk/iplayer/episode/m000g1rz/newsnight-05032020 |
| Description | BBC Radio Bristol Invincible Interview |
| 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 | Radion interview with BrisSynBio Director Professor Dek Woolfson and Kilter Theatre Director Oliver Langdon about the immersive, site specific, synthetic biology theatre, Invincible. Dr Phil Hammond's BBC Radio Bristol saturday Morningshow. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.bbc.co.uk/programmes/p05y3tjr |
| Description | BBI in Berlin: Better together |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Imre Berger, EPSRC SynBio CDT Student Julien Capin, and Bristol BioDesign Institute Scientific Manager Dr Kathleen Sedgley, were invited to present the Max Planck Bristol Centre for Minimal Biology at the British Embassy in Berlin on the 13 and 14 May 2019. Russel Group Universities' UK-Europe Knowledge Diplomacy Reception was opened by Chris Skidmore MP, and followed by a panel discussion Chaired by Dr Julie Maxton CBE, Executive Director of the Royal Society. The UK and Germany work together more than they work with any other country in Horizon 2020, in fact the UK is involved in over half of all German-led EU bids. Between 2013 and 2017 70,000 scientific publications were co-authored between academics in the UK and Germany, 2,177 (3.1%) of which involved the University of Bristol. Read more about the importance of UK-German collaboration, and the Max Planck Bristol Centre for Minimal Biology (page 11) of the Russell Group Knowledge Diplomacy Reception Brochure. The second event was organised in collaboration between BUILA (the British Universities International Liaison Association), and their German counterpart DAIA, (the Deutsche Assoziation für Internationalen Bildungsaustausch) supported by the British Council and Universities UK International. The Max Planck Bristol Centre for Minimal Biology was one of only 10 partnerships selected to to showcase collaborations between the UK, Germany and Europe. Here's the team with University of Bristol's Director International, Caroline Baylon. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://bristolbiodesign.blogs.bristol.ac.uk/category/bbi-events/ |
| Description | BBSRC PR: Designer barrel proteins |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Science publication, Computational design of water-soluble a-helical barrels [Science 24 October 2014: Vol. 346 no. 6208 pp. 485-488 DOI: 10.1126/science.1257452] was publicised on the BBSRC news page. Unknown. |
| Year(s) Of Engagement Activity | 2014 |
| URL | http://www.bbsrc.ac.uk/news/industrial-biotechnology/2014/141024-pr-bristol-team-creates-barrel-prot... |
| Description | Bath Royal Literary and Scientific Institution (led by postdoc Dr Lisa Buddrus) |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | In partnership with the Bath Royal Literary and Scientific Institution and with the support of the University of Bristol Public Engagement Office, I have run several hands-on workshops for children aged 11 to 13 around microbiology and biochemistry, introducing biotechnology, antimicrobials and antimicrobial resistance, and various aspects of hygiene and spread of infections. In partnership with the University of Bath (UoB), I also organised a workshop at the UoB Department of Biology and Biochemistry teaching labs, exploring DNA and synthetic biology. I was also involved in the events at We the Curious during World Antibiotic Awareness Week, demystifying appropriate antibiotic use and spread of antibiotic resistance with children of various ages. |
| Year(s) Of Engagement Activity | 2017,2018 |
| Description | BioIndustry Association SynBio special interest group |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | BrisSynBio invited attendance at the BioIndustry Association Synthetic Biology special interest group in May 2014. This group comprises SMEs, big business (including GSK and Syngenta) and and venture capitalists allied to synthetic biology. The meeting was also attended by the three Synthetic Biology Research Centres and SynBiCITE. Unknown. |
| Year(s) Of Engagement Activity | 2014 |
| URL | http://www.bioindustry.org/advisory-committees/synthetic-biology-advisory-committee-sbac/ |
| Description | Bright club Southampton: Do Scientists dream of Synthetic Sheep? (Heal) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Dr Jack Heal performs his stand up comedy show "Do Scientists dream of Synthetic sheep?" as the headline act at Bright Club, Southampton. Bright Club is a comedy night with researchers attempting to perform comedy about their work. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.southampton.ac.uk/per/university/bright-club.page |
| Description | ERASynBio workshop of the European Synthetic Biology Centres |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | The key results of this activity were to inspire and feed further ERASynBio developments and recommendations to the European Commission. None yet |
| Year(s) Of Engagement Activity | 2014 |
| URL | https://www.erasynbio.eu/ |
| Description | Engagement with industry |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Discussion with breeder regarding marker development for tracking introgressions |
| Year(s) Of Engagement Activity | 2017 |
| Description | Engagement with industry |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Meeting with service providers for genotyping technical development |
| Year(s) Of Engagement Activity | 2017 |
| Description | Engagement with industry |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Discussion with technology provider regarding optimisation of new technology for wheat |
| Year(s) Of Engagement Activity | 2018 |
| Description | Engagement with industry |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Transfer of markers to technology provider to aid the development of a new genotyping platform |
| Year(s) Of Engagement Activity | 2017 |
| Description | Engagement with industry |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Germplasm exchange for technical development |
| Year(s) Of Engagement Activity | 2017 |
| Description | Engagement with industry |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Meeting with technology provider regarding a new genotyping platform and its application |
| Year(s) Of Engagement Activity | 2017 |
| Description | Festival (Gorochowski) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Dynamic Cell Talk to members of the public attending Bristol International Balloon Fiesta. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Festival (Heal) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Green Man Festival: Do scientist dream of synthetic sheep? |
| Year(s) Of Engagement Activity | 2016 |
| Description | GARNet Gene Editing Workshop 26 -27 March 2018 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Plant gene editing workshop held at Bristol University. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Gene editing workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | Workshop speakers: John Dupré, Director of the ESRC Centre for Genomics in Society, University of Exeter: Responsible Research and Innovation in the field of gene editing Sabine Gokolok, Centre for Regenerative Medicine, University of Edinburgh: TALENS and gene editing in mammalian cells Lorenz Mayr, Vice President & Global Head, Biological reagents & Assay Development, AstraZeneca: CRISPR / Cas9 Nicola Paton, Head of Synthetic Biology, Sainsbury Laboratory: Gene editing in plants Workshop format: The morning consisted of talks from the above. We then asked our speakers to tell us about their difficulties and challenges in gene editing as well as their successes. This was followed by an open format during the afternoon where attendees had the opportunity to discuss techniques with the speakers. A small number of commercial suppliers also attended to demonstrate products and trouble shoot. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Gloucestershire college: Do Scientists dream of Synthetic Sheep? (Heal) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Talk/discussion to Biology students on the Access to Higher Education Course. Dr Jack Heal performs his stand up comedy show "Do Scientists dream of Synthetic sheep?". The audience will be students on an Access to Higher Education Course which is a one year course for adults without A Levels who wish to go to university. Most of them are intending to enter health professions. The show coincides with one of the lessons on the Biology course. All Biology students were invited to attend. |
| Year(s) Of Engagement Activity | 2016 |
| Description | International knowledge exchange (Sedgley) |
| 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 the Invincible theatre project to This delegation: engagement with public and industry |
| Year(s) Of Engagement Activity | 2017 |
| Description | Invited talk at the 2014 Gordon Research Conference on Tetrapyrroles (Rhode Island) |
| 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 work from my grant at the GRC tetrapyrroles meeting in Rhode Island in the summer of 2014. This was attended by many leading researchers in the heme and tetrapyrrole-containing protein field and represented an excellent opportunity to publicise my work amongst my peers. |
| Year(s) Of Engagement Activity | 2014 |
| URL | https://www.grc.org/programs.aspx?id=12064 |
| Description | Invited talk at the 67th Mosbacher Kolloquium (Protein design - from first principles to biomedical applications) in Mosbach, Germany |
| 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 my work at an international conference focussed on protein design, including all of the key founders and current leaders of the field. This resulted in many stimulating conversations with my peers and the scientific leaders in protein design and helped to promote the work of my group and the work performed in the grant. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://onlinelibrary.wiley.com/doi/10.1002/cbic.201600256/abstract?systemMessage=Pay+per+view+articl... |
| Description | Keynote presentation at 2019 Monogram |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Keynote, plenary lecture at Monogram 2019 |
| Year(s) Of Engagement Activity | 2019 |
| Description | Kilter Theatre production - Invincible |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | YouTube audience |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.youtube.com/watch?v=71K6h3wg1i8 |
| Description | Meeting with South African deligation to discuss meiosis, genotyping and wheat breeding |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Meeting with British Council lead South African delegation to discuss wheat breeding and possible further links |
| Year(s) Of Engagement Activity | 2018 |
| Description | Meeting with international experts in wheat breeding and recombination |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Meeting of international experts in wheat breeding and recombination/marker development to consider future prospects |
| Year(s) Of Engagement Activity | 2018 |
| Description | New Scientist Live (Paul Race) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | New Scientist Live 2018 Antibiotic discovery in the abyss Saturday 22nd September, Earth Stage Microbes are growing increasingly resistant to antibiotics, creating a global public health issue. The UK's strategy for overcoming this growing threat depends on the discovery and development of new antibiotics. Natural products have historically proven to be one of the most fruitful sources of antibiotics, with over half of all current clinically used antibiotics being derived from, or inspired by, natural products. In this talk, Paul Race outlines a major research project seeking to identify new antimicrobials from microorganisms that live in previously unexplored habitats on the seabed of the Atlantic Ocean, which can only be accessed using remotely operated robotic submersibles. This project is already yielding a rich diversity of novel antimicrobial agents that show promise for future use in public health. Paul Race is a senior lecturer in Biological Chemistry at the University of Bristol. He leads the EPSRC funded Manufacturing Immortality project, is a project lead within the BBSRC/EPSRC funded BrisSynBio Synthetic Biology Research Centre, was a founding Director of the Bristol BioDesign Institute, and is a co-founder and non-executive Director of the biomaterials spin-out company Zentraxa Ltd. His research focuses on the discovery and optimisation of natural product molecules as leads for new drugs and materials. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://live.newscientist.com/speakers/paul-race |
| Description | Panel Discussion (Bristol) "Synthetic Biology: Microbes, Plants and People" |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | "Exper panel" discussion on Synthetic Biology, based on questions and discussion from a non-specialist audience. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Parliamentary Science Committee presentation 2014 |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Approximately 200 people attended the Parliamentary and Scientific Committee meeting on the 17th June 2014. The audience included Parliamentarians, members of scientific bodies, science-based industry and academics. http://www.scienceinparliament.org.uk/sample-page/programme/ This meeting has subsequently been written up and included in the Autumn 2014 Science in Parliament (Vol 71 No 4: pgs 20 - 26) publication. Unknown |
| Year(s) Of Engagement Activity | 2014 |
| URL | http://www.scienceinparliament.org.uk/wp-content/uploads/2013/09/Autumn-Contents-page.pdf |
| Description | Pint of Science Festival - Where is your next meal coming from? (Edwards) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | A night on farming and food production of the future open to the public for debate, questions and discussions. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://pintofscience.co.uk/event/wheres-your-next-meal-coming-from |
| Description | Pint of Science Festival: Dark side of protein science |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | As part of the Pint of Science Festival, researchers from BrisSynBio participated in the 'Dark Matters' event. The event was held in Friska café, Bristol, and involved scientific crafts and discussions between researchers and the public. Director of BrisSynBio, Professor Dek Woolfson, along with Gail Bartlett, Jack Heal, Drew Thomson and Chris Wood organised the event 'Dark Matters'. Analogous to the idea of dark matter, protein science focuses on the protein structures that could theoretically exist but are not present in natural biology. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://www.bristol.ac.uk/publicengagementstories/stories/2015/dark-side-protein-science.html |
| Description | Pint of Science, Bristol, UK, May 2015, "From galaxies of stars to a new universe of proteins" |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Part of the Pint of Science 2015 Programme in Bristol. About 60 people attended. |
| Year(s) Of Engagement Activity | 2015 |
| URL | https://pintofscience.co.uk/event/dark-matters/ |
| Description | Public Engagement talk, Science controversy talk at the Smoke and Mirrors Pub, Bristol, 6th July 2016, Designer Babies and the use of gene editing, British Science Association |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Public understanding of science lecture in a local pub on designer babies and the future role of gene editing, including some interactive sessions to prompt discussion. Extensive discussion and opinion on the pros and cons of such technology |
| Year(s) Of Engagement Activity | 2016 |
| Description | Public dialog and debate |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | A pint of science debate on the price of bread and wheat breeding |
| Year(s) Of Engagement Activity | 2017 |
| Description | Public lecture (University of Bristol) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Public lecture to approx 200-300 people. Sparked interest in science, and discussion afterwards |
| Year(s) Of Engagement Activity | 2015 |
| Description | RCUK workshop on DNA synthesis |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Following the first phase of DNA Synthesis investments earlier in 2014, BBSRC, on behalf of the Research Councils, hosted a one day workshop to discuss mechanisms for implementing the second phase of capital investment (approximately £8M) for precompetitive DNA synthesis research/capabilities. The purpose of the capital money is to create a 'national capability' in DNA synthesis which will support the long term growth of UK synthetic biology. Attendees were required to complete a questionnaire in advance of the workshop identifying the (up to) five biggest research challenges for the next generation of DNA synthesis and the barriers to a coordinated state-of -the-art national capability. At the workshop attendees further considered what capability is already available and therefore what the existing requirements and bottlenecks for a UK capability are. The key outcome of the activity was the generation of a small number of short strategic cases for capital investment. These are currently being reviewed by BBSRC. Representatives from the private sector were also present at the workshop and it is anticipated that they will work closely with the academic community in the development of technologies that tackle challenges that underpin the next generation of DNA synthesis, but also in bringing the technologies/ capabilities developed closer to market/ into wider use. Long term there will be tangible impacts generated from the instruments purchased via this award if successful. The impact is likely to be mainly in the academic and industrial spheres, and in the areas of fine and speciality chemicals, pharmaceuticals, and life science technologies. |
| Year(s) Of Engagement Activity | 2014 |
| Description | RSC: Synthetic Biology: The Free Edinburgh Festival Fringe Show (Heal) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Supported by an award from the Royal Society of Chemistry,the Edinburgh Fringe Festival hosted its first science stand-up on the subject of synthetic biology. Jack Heal's 'Do Scientists Dream of Synthetic Sheep?' show took a comedic approach to genome engineering, de-extinction and more - with the crowd helping to shape its direction with questions and discussion. The show considered questions from artificial life to Jurassic Park, and ran for 21 days. Purpose: To interest the public in science. Outcome: The comic felt freshly enthused about doing [synthetic biology] research. Reflection: Free shows encourage people to take risks in their choices of which shows to see. This spirit is perfect for science outreach events which have to try hard to avoid becoming 'by scientists, for scientists'. None yet. |
| Year(s) Of Engagement Activity | 2014,2015 |
| URL | http://www.bristol.ac.uk/publicengagementstories/stories/2016/jack-heal.html?platform=hootsuite |
| Description | Radio Play - Blood Culture (Toye) |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Five 2-part 30 minute episodes in the form of an entertaining who-done-it including a post-show chat on the issues raised. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.blood-culture.com/audio.html |
| Description | Radio broadcast Farming today |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | Interview for farming today on wheat breeding and its importance; 14th July 2017 |
| Year(s) Of Engagement Activity | 2017 |
| Description | Rank Prize acceptance speech |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Rank prize (2018) acceptance speech |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.rankprize.org/index.php/prizes/prizes-2018 |
| Description | Rank Symposium on "The shape of wheat to come" |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | The Rank Symposium of "The shape of wheat to come" was a four day event organised by Edwards and Higgins to promote the area of recombination to a wide range of international scientists ranging from PhD students to retired professors |
| Year(s) Of Engagement Activity | 2018 |
| Description | Reverse Science Cafe |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | Reverse Science Cafe: Have your say your way This public event known as a "reverse science cafe" is where the scientists will be asking questions of the public. Tables Turned: Have a Say, Your Way Should we use engineered stem cells in therapy? When is it OK to release an engineered organism into the environment? Researchers working at the cutting edge of biological design need your help to decide how they work and what they make in the future. Join researchers from BrisSynBio in a discussion event exploring the ethical and societal issues related to research that is taking place at the University of Bristol on genetic engineering. Researchers will share some of the challenges they are facing and will work with you to find potential solutions |
| Year(s) Of Engagement Activity | 2018 |
| Description | SBLC SBRC subgroup |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Accepted membership of the BIS commissioned Synthetic Biology Leadership Committee, Synthetic Biology Research Centre sub group. The first meeting of this group took place on May 2014. This was attended by the following: Jim Hasslehoff, Cambridge Nigel Minton, Nottingham John Ward, UCL Paul Freemont, Imperial Dick Kitney (chair), Imperial John Collins, Imperial Paul Race, BrisSynBio Bristol Anne Osbourn, John Innes Centre Kathleen Sedgley, BrisSynBio Bristol The purpose of this meeting was to share information about the three SBRCs and SynBiCITE to feed up to BIS via the SBLC. This will be an ongoing activity. Unknown. |
| Year(s) Of Engagement Activity | 2014 |
| 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 (Caldicott School) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Talk attended by ~ 40 year 12 and 13 students at Caldicott School, which sparked questions and discussion afterwards. |
| Year(s) Of Engagement Activity | 2015 |
| Description | School engagement (Gorochowski) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Teaching antimicrobial concepts using interactive biofilm in virtual reality: Developed in collaboration with Clevedon School, Somerset. |
| Year(s) Of Engagement Activity | 2017 |
| Description | School visit (Beechen Cliff) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Talk given at Beechen Cliff School to year 12 students, with questions and discussion afterwards. |
| Year(s) Of Engagement Activity | 2019 |
| Description | School visit (QEH school) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Talk given at QEHSchool to year 12 students, with questions and discussion afterwards. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Schools Visit (Warminster School) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Talk sparked questions and discussion. Positive feedback from staff and pupils. |
| Year(s) Of Engagement Activity | 2013 |
| Description | Sci-Art collaboration (Connor) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Knowledge link through Art and Science workshop, Max Planck led. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Sci-art collaboration (Toye) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | Blood culture: reimage(in)ing life at a cellular scale. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://katyconnor.wordpress.com/ |
| Description | Science Cafe - Synthetic biology - creating artificial enzymes (Anderson) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | British Science Association: Bristol and Bath branch. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Science Cafe: Lab grown blood becomes a reality (Toye) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | BrisSynBio researchers are growing blood in the laboratory; work that will have potentially profound effects for patients needing regular transfusions, or rare types of donated blood in the future. This Science Café on blood production was presented by a panel of experts including Professor David Anstee from the NHS Blood Service and biochemists Dr Ashley Toye, BrisSynBio, and Dr Jan Frayne from Bristol University. Outcome: Attendees learnt how scientists aim to use this blood to study rare diseases, engineer new therapeutic qualities by using synthetic biology, and offer an alternative to patients with certain conditions. |
| Year(s) Of Engagement Activity | 2016 |
| Description | SoapBox Science London Southbank |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | From the web site: "The UK's leading female scientists take to their soapboxes to showcase science to the general public. The event's mission remains the same: to help eliminate gender inequality in science by raising the profile, and challenging the public's view, of women and science." I spoke about "Synthetic Biology - Designing Life". An estimated 3000 people attended. There was lively discussion including comments from people who told me they were professional regulators. It was a very well informed two-way conversation with a people ranging from toddlers in push chairs to the elderly in wheelchairs. The experience diffused a lot of my fears about engaging with he public about this controversial topic, leading me to take on more public engagement work about synthetic biology. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://soapboxscience.org/soapboxscience-2015-london/ |
| Description | Stakeholder Workshop: Social Responsibility and Wheat Research 13/9/18 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Stakeholders talked about their own interests (and/or those of their community) in relation to the many uses of wheat. The event also considered stakeholder responses as the basis for a report on social responsibility and wheat research targeted at policy audiences |
| Year(s) Of Engagement Activity | 2018 |
| Description | SynBioExpo (Space Gallery, Bristol). |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | A collaborative exhibition between Bristol-based artists Imogen Coulter, Claudia Sticker and Theo Wood and researchers at BrisSynBio, exploring the possibilities and ethical questions of CRISPR. Curated and organised by Grace Mullally. Feedback from the public about the challenging questions surrounding gene editing were collected. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://theislandbristol.com/event/synbioexpo/ |
| Description | Synthetic Biology Research Centres Ethical Legal and Social Aspects meeting |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | This was a BBSRC hosted one-day ELSA workshop for the SBRC grant holders to ensure they incorporate appropriate and meaningful ELSA consideration into their Centres. Additionally the workshop networked the SBRCs and the broader synthetic biology community including the EPSRC-BBSRC synthetic biology CDT. The main results of the activity were to share the ELSA plans across the SBRCs, exploration of strengths and challenges. Joint publications between SynBio researchers and social scientists will be a measurable metric of success in this for the SBRCs. None yet |
| Year(s) Of Engagement Activity | 2014 |
| Description | Synthetic Biology through different lenses |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Panel discussion exploring synthetic biology through different lenses: Claudia Stoker, Illustrator, Vivid Biology Nick Matthews, Social Scientist, SYNBIOCHEM Jim Scown, Environmental Humanities, Cardiff and Bristol Cassidy Nelson, Future Humanities Institute |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://synbioukac.wixsite.com/synbiouk |
| Description | Synthetic proteins for a synthetic biology: faster, fitter, stronger |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Better Humans Science Café, Bristol, UK, October 5 2016, "Synthetic proteins for a synthetic biology: faster, fitter, stronger" |
| Year(s) Of Engagement Activity | 2016 |
| Description | The rise and rise of synthetic biology in the UK: science, policy and public perception |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Invited to Houses of Parliament, London, UK, June 2014, to speak to the Parliamentary and Scientific Committee. |
| Year(s) Of Engagement Activity | 2014 |
| URL | http://www.scienceinparliament.org.uk/wp-content/uploads/2014/05/17-June-AGM-agenda.pdf |
| Description | The value of naturalness in the age of marvelous technologies (Meacham) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | On 16 April 2015, BrisSynBio hosted a public debate at Bristol's Watershed Arts Centre on the "value of naturalness in the age of marvelous technologies." Sir Roland Jackson from the Nuffield Council on Bioethics, Professor Alison Assiter from UWE, Bristol, Professor Nima Yeganefar from the Université de Poitiers and a lively audience discussed and debated in the role of the concepts of "nature" and "naturalness" in ethical and political discourse surrounding emerging biotechnologies. The event was organised and chaired by Darian Meacham. Sir Roland Jackson blogged about the event: http://nuffieldbioethics.org/blog/2015/why-do-we-value-naturalness-a-lively-discussion/ The debate was sponsored by UWE's Social Science in the City, The Royal Institute of Philosophy in collaboration with the Bristol Festival of Ideas. |
| Year(s) Of Engagement Activity | 2015 |
| URL | https://www.youtube.com/watch?v=rk25Fl4ajEY |
| Description | Tools and Developments for DNA Synthesis |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | BrisSynBio attendance at a SynBiCITE hosted workshop jointly organised by Thermo Fisher Scientific, which incorporates Life Technologies and gene Art. Early stage discussions initiates with Gene Art around the use of their technologies throughout BrisSynBio and longer term development projects. Meeting planned for early 2015. Early stage discussions initiated with Midven venture capitalists about potential investment opportunities arising from BrisSynBio. Meeting planned for December 2014. |
| Year(s) Of Engagement Activity | 2014 |
| Description | UCAS Open Day |
| 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 | Schools |
| Results and Impact | Participation in the School of Biochemistry UCAS open day. Demonstration of single molecule magnetic tweezers. |
| Year(s) Of Engagement Activity | 2017 |
| Description | UCAS post offer day |
| 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 | Schools |
| Results and Impact | Participation in the School of Biochemistry UCAS post-offer day. Demonstration of single molecule magnetic tweezers and talk about genome editing. |
| Year(s) Of Engagement Activity | 2017 |
| Description | UCL Chemical and Physical Society evening talk: Do Scientists dream of Synthetic sheep? (Heal) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Dr Jack Heal performed his stand up comedy show "Do Scientists dream of Synthetic sheep?" to UCL Chemical and Physical Society. CPS was founded in 1876 and is believed to be the oldest scientific student body in the country. It is run predominantly by students and hosts lectures weekly throughout term time as well as organising many other events for students and staff throughout the year. The lecture programme has a general science remit and our audience mainly comprises staff and students of the chemistry department (as well as a growing cohort of natural science students) and members of SCI London, who sponsor the society. |
| Year(s) Of Engagement Activity | 2016 |
| Description | University of Bristol Open Days |
| 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 | Public/other audiences |
| Results and Impact | One-to-one discussions with members of the public about our research, biochemical sciences generally, and other aspects of University study. It is difficult to report specific impacts. I have no doubt that the discussions influenced the life choices of many of the young people that I spoke with. |
| Year(s) Of Engagement Activity | 2007,2008,2009,2010,2011,2012,2013,2014,2015 |
| Description | We the Curious, Bristol, UK, September 2019, Futures 2019 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Woolfson gave an interactive talk on protein design and synthetic biology to a general as part of Bristol Futures 2019 at We the Curious, Bristol, UK, in September 2019. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.futures2019.co.uk/events/we-the-curious/ |
| Description | Women in Science Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Around 100 children from local secondary schools were invited to participate in a number of live science demonstrations held in the Anson room at the University of Bristol's Students Union Building. Staff and students from across the University organized the live science demonstrations with children actively encouraged to ask questions and take part. I spoke to groups of schoolchildren and their teachers asking them questions about their perceptions of the history of human impacts on the natural world, human self-improvement, and what they think the future implications of synthetic biology might be. |
| Year(s) Of Engagement Activity | 2015,2016,2017 |
| URL | https://www.bristol.ac.uk/translational-health-sciences/news/2017/women-in-science-outreach-event.ht... |
| Description | Women in Science Day - Designing Life (Grierson) |
| 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 | 100 school pupils and their teachers were the audience for this talk, prompting questions and discussion about ethical issues in science. |
| Year(s) Of Engagement Activity | 2017 |
| Description | You tube (Meacham) |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Professor Dek Woolfson speaks about the potential of Synthetic Biology. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.youtube.com/watch?v=4tcyPej7hos |
| Description | You tube (Meacham) |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Dr Darian Meacham raises philosophical questions in the context of biology about what we regard as 'natural' and how this relates to the way we think about Synthetic Biology and the role of public engagement in science. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.youtube.com/watch?v=y1no4L1dfhU |
| Description | You tube (Meacham) |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Professor Dek Woolfson (Synthetic Biology researcher) and Dr Darian Meacham (Philosopher) discuss responsible research and innovation within Synthetic Biology. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://www.youtube.com/watch?v=ARUtqdLQf2Q |