SynthSys-Mammalian: Edinburgh Mammalian Synthetic Biology Research Centre

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

The vision for Edinburgh's Centre for Mammalian Synthetic Biology (SynthSys-Mammalian) is to pioneer the development of the underpinning tools and technologies needed to implement engineering principles and realise the full potential of synthetic biology in mammalian systems. We have an ambitious plan to build in-house expertise in cell engineering tool generation, whole-cell modelling, computer-assisted design and construction of DNA and high-throughput phenotyping to enable synthetic biology in mammalian systems for multiple applications. In this way we will not only advance basic understanding of mammalian biology but also generate tools and technologies for near-term commercial exploitation in areas such as the pharmaceutical and drug testing industries, biosensing cell lines sensing disease biomarkers for diagnositics, novel therapeutics, production of protein based drugs e.g. antibodies and also programming stem cell development and differentiation for regenerative medicine applications. In parallel we will develop and implement new understanding of the social and economic impact of this far-reaching technology to ensure its benefits to society.

Technical Summary

Synthetic biology (SB) is defined in the UK Synthetic Biology Roadmap1 as 'the design and engineering of biologically based parts, novel devices and systems as well as the re-design of existing natural biological systems.' SB is both a platform technology and a translational technology (providing the link between a wide range of underpinning disciplines - ranging from biochemistry to systems biology - and practical applications in a wide range of different market sectors). We aim to pioneer the development of the underpinning tools and technologies needed to implement engineering principles and realise the full potential of synthetic biology in mammalian systems. We will 1. Establish a robust pipeline for the production and screening of synthetic transcription factors (sTFs) and synthetic chromatin editors (sCEs) based on the DNA binding domains of TAL effectors (TALEs) and the CRISPR/Cas system fused to transcriptional activators, repressors or chromatin modifiers e.g. histone deacetylases. 2. Create an in silico tool for designing small-molecule control of engineered protein and demonstrate the utility of this tool by producing novel drug-controlled proteins. 3. Assemble synthetic chromosomes and chromosomal safe harbors for introduction of synthetic genetic circuits. 4. Reduce contextual effects by building predictive models through characterizing circuit-chassis interactions at the single-cell level. 5.Engineer memory and computation synthetic genetic circuits in mammalian cells to a) deliver mechanistic information on the cell state, and responses to perturbations, e.g. drug treatments and count cell divisions. Underpinning this will be the development of standards for mammalian synthetic biology in collaboration with our partners NPL and take the concept of RRI in new directions to include: the politics of standardisation; the use of strategic mapping methodologies; and new approaches to engagement informed by speculative design.

Planned Impact

The SBRC focuses on building mammalian engineering capacity to benefit the life sciences, biotechnology and biomedicine.

Our deliverables for engaging with stakeholders are:

1) Through community building we will increase membership of the SBRC and double our total collaborative research income by Year 5. We will reach out locally by continuing Open Centre Meetings (fortnightly), organise monthly PI lunches preceded by a PI seminar, record seminars and both live webcast and disseminate online, hold an annual Away Day, publish a monthly newsletter, and further explore novel ways of engagement.

2) To be an internationally recognised brand with a reputation as a centre of excellence in synthetic bioengineering of mammalian systems. To do so, we will strengthen links to local networks for national phenotyping and regenerative medicine, champion the iGEM competition, continue to be active participants in three RCUK networks, link with other SBRCs and DNA Synthesis Centres, build additional international links (particularly in China, Korea, and Hong Kong), and work to host the meeting for the international synthetic yeast genome project and SynBioBeta.

3) By Year 5, we will have created an innovation environment for synthetic biology that balances the objectives and concerns of public, industry, policy, and academic communities. We will set up a Stakeholder Forum with members from industry, policy makers, regulators, and investors; maintain high visibility at Science Festivals; deepen our involvement in art-in-science events; host a writer in residence to help communicate our research; continue to make best use of the University's Press Gangs and Officers; maintain a dynamic suite of websites, have a Twitter account, and all researchers will create and promote "Research in a Nutshell" BioPodcasts; arrange 6-monthly, off-site, SynthSys Cafes to foster engagement and build dialogue; raise the profile of our activity across government through invitations to MSPs, Chief Scientists and NGOs; and maintain and grow international influence through our membership of government leadership committees. We will create a community of activity around the SBRC with at least two industrial SBRC members participating in training activities and in reciprocal secondment of staff.

A further key impact will be to generate highly skilled, responsible, and enthusiastic scientists and engineers that will move into research, management, or operational roles in private and public sectors, building the UK's capacity in synthetic biology.

We anticipate the generation of considerable intellectual property (IP) of commercial value. We will draw on Edinburgh Research and Innovation Business Development Executive, our International Advisory Board, our industrial partners, and the strength of our broader industrial network to expedite the translation of IP. We are a key partner of the Synthetic Biology Innovation Commercial and Industrial Translation Engine (SynbiCITE) and are heavily involved in both the Scottish Industrial Biotechnology Innovation Centre and the CENSIS Innovation Centre in Sensor and Imaging Systems. We will target new market sectors by developing marketing materials tailored to specific industries, holding an annual Industry Information Day to consolidate and broaden our links, and by developing an industry-engagement plan to meet industry through site visits, missions overseas and industry partnering events. By year 5, we plan three innovations in early stages of product development and to be in advanced discussion with 3-4 industry partners around R&D collaborations.

Finally, in addition to academic impacts through refereed journals and presentations at international conferences, SBRC outputs will be published in industry and policy journals, talks at national and international festivals, in media presentations, and through a portfolio of policy briefing notes that are widely distributed.

Publications

10 25 50
 
Description The vision for the UK Centre for Mammalian Synthetic Biology (the 'Centre') at the University of Edinburgh is to pioneer the development of the essential tools and technologies needed to realize the full potential of synthetic biology for mammalian cell biology and human medicine. We remain convinced that this is a relevant, exciting and ambitious area for synthetic biological engineering and one in which we can forge a unique position. The Centre was officially launched on October 7th at a day-long event attended by over 100 delegates from academia, industry and government/NGOs. Our Leadership and Management team has worked hard this year to raise the profile of our new Centre both in the UK and internationally. They have represented the Centre at numerous national and international research and industry conferences over the year, notably the Mammalian
Synthetic Biology workshop in Boston, Synthetic Biology: Engineering, Evolution & Design (SEED) in Boston, Innovate UK, SynBioBeta in London and San Francisco (including a UKTI Trade Mission), a workshop at the National University of Singapore, and at Biomanufacturing Sheffield.
Despite some challenges in hiring suitably qualified staff in a timely manner, our research programme and spend is largely on schedule. We have made good progress in Work Theme 1 around tools development, with success in generating libraries of synthetic transcription factors and with developing 'drugable' protein modules. Although still early for substantive research outputs, we are encouraged at our first publication (on automation of DNA synthesis) and several others in preparation. Research activity and outputs will accelerate over the coming year.
Our first patent - of a rapid and cheap method for the production of synthetic transcription factors, the so-called STAR method - is filed and currently under licensing negotiations. One commercial collaboration (with IDT) for a multiplexing technology is under discussion.
We have proactively engaged industry through attending and exhibiting at conferences and site visits. The activities of the Centre are very interesting to industry: Over the past year, we have hosted visits from 16 companies that we had not previously engaged with and we will continue dialogue with them towards building collaborations for the future. One area not in the original Case for Support, but nevertheless of keen industry interest, was the application of the synthetic biology tools for bioproduction (e.g. biologics in CHO cells); we will incorporate this into the Centre research activities as a parallel work stream seeking funding from alternative sources (e.g. IB Catalyst, private funding).
Over the year we engaged with policy and strategy in synthetic biology development: The management team and PIs participated in the Synthetic Biology Roadmap Consultation (Birmingham, June); Professor Joyce Tait is active on the Synthetic Biology Leadership Council and had significant involvement in the drafting of the Strategic Plan for Synthetic Biology (Roadmap Refresh) and she is appointed to the US NAS Advisory Committee on 'Reprogramming Non-human Populations using "Gene Drives": Recommendations for Responsible Conduct.'
The creation of the Centre has drawn much attention both internally and externally, which has stimulated both new conversations and working collaborations: Professor Rosser is leading on a full application for a £5M BBSRC sLoLa award with five other PIs from across the University (two not on the original Centre grant); She is a Co-I on a £3M Innovate UK grant with the University of York; and Centre PIs have been awarded ~£200K of internal funds to kick-start several new projects.
We are keen to support growth of the synthetic biology community outside of the South East of the UK and hosted the first SynBioBeta Activate! Event in Scotland, drawing a sell-outcrowd of >100 academic and industry delegates. Regular engagement with SynbiCITE, through participation in events such as LEAN Launchpad, 4-Day MBA and other organised events, keeps us integrated with the wider UK community.
Exploitation Route Our first patent - of a rapid and cheap method for the production of synthetic transcription factors, the so-called STAR method - is filed and currently under licensing negotiations. One commercial collaboration (with IDT) for a multiplexing technology is under discussion.
We have proactively engaged industry through attending and exhibiting at conferences and site visits. The activities of the Centre are very interesting to industry: Over the past year, we have hosted visits from 16 companies that we had not previously engaged with and we will continue dialogue with them towards building collaborations for the future. One area not in the original Case for Support, but nevertheless of keen industry interest, was the application of the synthetic biology tools for bioproduction (e.g. biologics in CHO cells); we will incorporate this into the Centre research activities as a parallel work stream seeking funding from alternative sources (e.g. IB Catalyst, private funding).
Over the year we engaged with policy and strategy in synthetic biology development: The management team and PIs participated in the Synthetic Biology Roadmap Consultation (Birmingham, June); Professor Joyce Tait is active on the Synthetic Biology Leadership Council and had significant involvement in the drafting of the Strategic Plan for Synthetic Biology (Roadmap Refresh) and she is appointed to the US NAS Advisory Committee on 'Reprogramming Non-human Populations using "Gene Drives": Recommendations for Responsible Conduct.'
Sectors Agriculture, Food and Drink,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description The vision for the UK Centre for Mammalian Synthetic Biology (the 'Centre') at the University of Edinburgh is to pioneer the development of the essential tools and technologies needed to realize the full potential of synthetic biology for mammalian cell biology and human medicine. We remain convinced that this is a relevant, exciting and ambitious area for synthetic biological engineering and one in which we can forge a unique position. The Centre was officially launched on October 7th at a day-long event attended by over 100 delegates from academia, industry and government/NGOs. Our Leadership and Management team has worked hard this year to raise the profile of our new Centre both in the UK and internationally. They have represented the Centre at numerous national and international research and industry conferences over the year, notably the Mammalian Synthetic Biology workshop in Boston, Synthetic Biology: Engineering, Evolution & Design (SEED) in Boston, Innovate UK, SynBioBeta in London and San Francisco (including a UKTI Trade Mission), a workshop at the National University of Singapore, and at Biomanufacturing Sheffield. Despite some challenges in hiring suitably qualified staff in a timely manner, our research programme and spend is largely on schedule. We have made good progress in Work Theme 1 around tools development, with success in generating libraries of synthetic transcription factors and with developing 'drugable' protein modules. Although still early for substantive research outputs, we are encouraged at our first publication (on automation of DNA synthesis) and several others in preparation. Research activity and outputs will accelerate over the coming year. Our first patent - of a rapid and cheap method for the production of synthetic transcription factors, the so-called STAR method - is filed and currently under licensing negotiations. One commercial collaboration (with IDT) for a multiplexing technology is under discussion. We have proactively engaged industry through attending and exhibiting at conferences and site visits. The activities of the Centre are very interesting to industry: Over the past year, we have hosted visits from 16 companies that we had not previously engaged with and we will continue dialogue with them towards building collaborations for the future. One area not in the original Case for Support, but nevertheless of keen industry interest, was the application of the synthetic biology tools for bioproduction (e.g. biologics in CHO cells); we will incorporate this into the Centre research activities as a parallel work stream seeking funding from alternative sources (e.g. IB Catalyst, private funding). Over the year we engaged with policy and strategy in synthetic biology development: The management team and PIs participated in the Synthetic Biology Roadmap Consultation (Birmingham, June); Professor Joyce Tait is active on the Synthetic Biology Leadership Council and had significant involvement in the drafting of the Strategic Plan for Synthetic Biology (Roadmap Refresh) and she is appointed to the US NAS Advisory Committee on 'Reprogramming Non-human Populations using "Gene Drives": Recommendations for Responsible Conduct.' The creation of the Centre has drawn much attention both internally and externally, which has stimulated both new conversations and working collaborations: Professor Rosser is leading on a full application for a £5M BBSRC sLoLa award with five other PIs from across the University (two not on the original Centre grant); She is a Co-I on a £3M Innovate UK grant with the University of York; and Centre PIs have been awarded ~£200K of internal funds to kick-start several new projects. We are keen to support growth of the synthetic biology community outside of the South East of the UK and hosted the first SynBioBeta Activate! Event in Scotland, drawing a sell-outcrowd of >100 academic and industry delegates. Regular engagement with SynbiCITE, through participation in events such as LEAN Launchpad, 4-Day MBA and other organised events, keeps us integrated with the wider UK community.
First Year Of Impact 2016
Sector Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
 
Description Keck Futures Initiatives
Amount $50,000 (USD)
Organisation W M Keck Foundation 
Sector Charity/Non Profit
Country United States of America
Start 06/2015 
End 06/2017
 
Title synPHARM 
Description SynPharm is a database of ligand-responsive protein sequences, derived from interactions from the Guide to PHARMACOLOGY and using data from the Protein Data Bank. The sequences here are obtained by identifying the protein chain that interacts with a ligand for a given Guide to PHARMACOLOGY interaction, determining the binding residues, and producing a continuous 'bind sequence' that can be used to confer drugability to another protein. Each bind sequence also contains metrics such as atomic contact ratio and proportional length, and visualisations such as the residue distance matrix, to allow you to better judge whether a sequence is likely to be able to fold independently. The rationale for such a project was to enable the development of orthogonal molecular switches - switches which only respond to an exogenous molecular trigger, which itself will not interfere with endogenous receptors. 
Type Of Material Data analysis technique 
Year Produced 2016 
Provided To Others? Yes  
Impact Text written March 2017: We have used the tool to generate druggable versions of Cas9 and cpf1 for inducible gene editing (paper in preparation). The database was put on full public release so recently that we are not yet aware of external impacts, but we have just added a Google Analytics counter to track external use. 
URL http://synpharm.guidetopharmacology.org/
 
Title Fitderiv 
Description The software is written to provide a tool for estimating growth rates from optical density data and uses that language (although it can process any other type of data too). It has been described in more detail in the following publication Swain P S**, Stevenson K, Leary A, Montano-Gutierrez L F, Clark I B N, Vogel J and Pilizota T. Inferring time-derivatives, including cell growth rates, using Gaussian processes. Nature Communications 2016;7:13766 and made openly available at http://swainlab.bio.ed.ac.uk/software/fitderiv/ 
Type Of Technology Software 
Year Produced 2016 
Impact The software is currently used by several research groups and expected to be adopted wider (publication date is December 2016) 
URL http://swainlab.bio.ed.ac.uk/software/fitderiv/
 
Description BBC Arabic TV Visit 
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 Visit from Anees Al Qudaihi, from BBC Arabic World Service, who was making a future edition of a Science and Technology programme.
Year(s) Of Engagement Activity 2016
 
Description Edinburgh Doors Open Day 2015 
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 On September 26th, SynthSys opened the Waddington Building to the public for the first time during the Doors Open event. Over the course of the day we had 75 visitors come to explore about our multidisciplinary research that brings biology together with engineering. We had exhibits from the lab of Dr Timm Krueger who offered hands-on interactive on a novel method for sorting cells, useful potentially in medicine. The lab of Prof Chris French explained how cells can be engineered to detect arsenic in drinking water, a project that may help the 100 million people at risk in developing countries. Members from the lab of Dr Patrick Cai offered a fun demonstration of the value of high-throughput and automated technology for printing cells (see photos). Dr Louise Horsfall's lab treated guests to the wonders of fluorescent bacteria and how bugs can be designed to clean up contaminated soil. Finally, visitors could actually check for themselves how climate change impacts on plant growth by playing with parameters of a model generated in the lab of Professor Andrew Millar. Edinburgh Doors Open Day is organised by the Cockburn Association (Edinburgh's Civic Trust). Now in its 25th year, the event has become one of the capital's most popular free days out. For the day Edinburgh's most architecturally, culturally and socially significant buildings are opened to the public. Many of our visitors asked probing questions about our research and several were potential undergraduate students considering training in synthetic biology.
Year(s) Of Engagement Activity 2015
URL http://www.synthsys.ed.ac.uk/news/opening-doors-synthsys
 
Description Edinburgh Doors Open Day 2016 
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 Over 70 visitors enjoyed learning about synthetic biology and its many applications at the Edinburgh Doors Open event in the Roger Land Building on Saturday 24th at the King's Buildings Campus. Staff and postgraduate students from SynthSys, and this year's Edinburgh iGEM team, came along to explain more about their research and the power of synthetic biology. They were joined by staff from the Centre for Regenerative Medicine, who explained how stem cells are being used to create cells suited for therapy. Children had an opportunity to engineer their own fuzzy felt bugs, parents contemplated stem cells under a microscope and visitors were amazed at the metal munching power of microbes. Many of our visitors were quite unaware of the work we do and its potential impact for society. There were many animated conversations from both adults and children about synthetic biology.
Year(s) Of Engagement Activity 2016
URL http://www.synthsys.ed.ac.uk/news/open-doors-synthetic-biology
 
Description Edinburgh International Science Festival 
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 The Centre took synthetic biology to the Edinburgh Science Festival from March 31st to April 4th. Part of the School of Biological Science's 'Biodiscoveries' activities, the Centre sought to explain the fundamentals of synthetic biology to the primary school age visitors and their carers and to showcase some of the exciting research projects underway in Edinburgh. Over 2,500 attended the event, with lots of questions and interactions from the young visitors.
Year(s) Of Engagement Activity 2016
URL http://www.synthsys.ed.ac.uk/news/fuzzy-felt-festival-science
 
Description Exhibitor at 2016 Industrial Biotechnology Showcase 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Centre showcased its research activities and industry partnerships to over 400 delegates attending the annual conference of the Industrial Biotechnology Innovation Centre (IBioIC) in Glasgow on January 28th and 29th. We had a stand within the exhibition hall displaying pop-up banner and marketing materials. Professor Susan Rosser, Director of the Centre for Mammalian Synthetic Biology, chaired a session on the challenges and opportunities arising from synthetic biology. The meeting generated many new leads with key industry players and other potential academic collaborators.
Year(s) Of Engagement Activity 2016
URL http://www.synthsys.ed.ac.uk/news/synthsys-exhibits-annual-industrial-biotechnology-innovation-centr...
 
Description Exhibitor at SynBioBeta London 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact The Centre had a stand at SynBioBeta in London April 2016 alongside our other sister BBSRC funded SynBio Research Centres. Several hundred delegates attended from the UK and overseas. The meeting enabled us to network with other colleagues from across the UK and beyond, network with industry executives and investors and also better understand the commercial synbio landscape.
Year(s) Of Engagement Activity 2016
URL http://www.synthsys.ed.ac.uk/news/synbioblog-synbiobeta-london-2016
 
Description Formal Launch of the UK Centre for Mammalian Synthetic Biology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact The Centre was officially launched on October 7th at a day-long event attended by over 100 delegates from academia, industry and government/NGOs. There was an overview of the vision of the centre and some of the key work packages. One of our Board members provided a keynote talk and discussion by industry. During the event we also hosted first SynBioBeta Activate event in Scotland with over 80 attendees.
Year(s) Of Engagement Activity 2015
URL http://www.synthsys.ed.ac.uk/news/uk-centre-mammalian-synthetic-biology-launched
 
Description Foundry official launch event 
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 To celebrate the EGF opening, the University hosted a second SynBioBeta Activate! event in Scotland in partnership with Scottish Enterprise. This event attracted nearly 200 delegates and delivered a lively afternoon of discussion and debate on the role of automation and robotics in synthetic biology. There was a lineup of distinguished international speakers with an inspiring keynote from Ye Yin, CEO of BGI who talked about their ambitious plans in synthetic biology. Delegates then enjoyed short presentations from some of the leaders in DNA design and assembly automation including Cambridge Consultants, Labcyte, Thermo Scientific, Pacific Biosciences, Autodesk, m2p Labs.
Year(s) Of Engagement Activity 2016
URL http://www.synthsys.ed.ac.uk/news/edinburgh-map-dna-design-and-construction
 
Description MSP visit to Foundry 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact Visit from local MSPs Ian Murray and Daniel Johnson
Year(s) Of Engagement Activity 2016
 
Description Midlothian Science Festival 2016 
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 We took our 'Master Biobuilder' to he Midlothian Science Festival over a weekend in October. This enables us to reach out to less advantaged regions around Edinburgh and share our interest in Synthetic Biology. There was good engagement as this event from visitors.
Year(s) Of Engagement Activity 2016
 
Description Science Art Writing Training for Schools 
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 A group of 20 teachers, scientists, poets and artists went 'back to school' to learn the SAW Trust's innovative approach to teaching science with a view to applying this in schools. Over May/June they then developed and delivered innovative workshops for primary school children in five local schools. This was a great success and all schools felt that the activities enriched their teaching of the science subjects. Several schools are interested in participating again.
The activity has also enabled further engagement with key members of local education authority and Councis looking to better work with Higher Education and around the area of creativity and multidisciplinarity.
Year(s) Of Engagement Activity 2016
URL http://www.synthsys.ed.ac.uk/news/saw-trust-inspires-science-art-workshop