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SYNTHETIC BIOLOGY – ENGINEERING BIOLOGY AT IMPERIAL COLLEGE HISTORY Professor Richard Kitney: Co-Director of the Centre for Synthetic Biology and

Professor Paul Freemont: Co-Director of the Centre for Synthetic Biology and Innovation

Preliminary research in synthetic biology started at Imperial College London in 2004. In 2005 Professors Richard Kitney and Paul Freemont were awarded an internal grant by Imperial to establish a laboratory for synthetic biology research.

In addition to Kitney and Freemont, this PhD students - from the Life Sciences, Many international observers now comprised a handful of PhD students - Engineering and the Natural Sciences consider CSynBI to be one of the leading plus the part-time assistance of Kirsten departments. They were supported by international centres for research in Jensen as the laboratory manager. The the Science and Innovation Award and synthetic biology, indeed its international work of the laboratory, with limited funds, subsequently by a range of other grants influence is considerable. CSynBI has grew steadily until 2008. It was during made possible by the existence of CSynBI. been proud to welcome international this year that the Research Councils Within Imperial there are around another delegations from countries such as launched a call for synthetic biology as 40 scientists and engineers working , China and Singapore (including part of the programme for Science and on projects associated with CSynBI the Singaporean Economic Development Innovation Centres aimed at building demonstrating its collaborative reach. Board) and assist them in their synthetic academic capacity. Imperial’s application In addition, Professor Nik Rose and biology policy development. was successful and in the spring of collegues from the Department of Social Members of the Centre (principally 2009 the EPSRC Centre for Synthetic Science, Health and Medicine, at King’s Professors Kitney and Freemont) have Biology and Innovation (CSynBI) was College London study the responsible been heavily involved in the development established. CSynBI’s strategy is one of innovation issues (i.e. societal, ethical and of synthetic biology strategy for the UK. applying engineering to biology by way environmental considerations) relating to of systematic design. This involves the synthetic biology. application of the engineering principles The Centre’s collaborative reach is now of modularity, standardisation and international and it has strong links with characterisation - via the development the , including Stanford of platform technology - to a range of University and UC Berkeley - as well as applications. being a key member of European grants. CSynBI’s capacity has continued to It has significant ongoing collaboration build and expand and it now comprises with NTU and NUS in Singapore. 10 PIs and around another 60 researchers - consisting of Postdoctoral and In 2008 Professor Kitney chaired a published in July 2012. Both Kitney and written agreement between the groups. In Royal Academy of Engineering inquiry into Freemont made significant contributions the spring of 2012 the Flowers Consortium synthetic biology, which was published in to both the development of the strategy was awarded a significant grant by EPSRC May 2009. and the writing of the Roadmap. Again, for the specific purpose of developing this document has been influential platform technology (sometimes called Professor Freemont was also a key internationally. foundational technology) for synthetic member of the inquiry. The report of biology. the inquiry has been, and remains, Also in 2011, CSynBI organised a two- influential in the development of day workshop at Imperial College for the This project has been running synthetic biology strategy in many groups involved in synthetic biology at for two and a half years and last countries. In the autumn of 2011 the Rt the Universities of Cambridge, Edinburgh, summer underwent a full review by its Hon MP, the then Minister Newcastle and Kings College London. international advisory board - which of State for Universities and Research, The aim was to broaden activities to comprises leading synthetic biologists organised a roundtable discussion at encompass the additional strengths of from the United States and Europe. As the UK Government’s Department of these universities in the area of synthetic a result of the strength of the research Business Innovation and Skills to which biology. The plan was to establish a within the Flowers Consortium, CSynBI both Kitney and Freemont were invited. consortium of research activity. was invited to become a member of One of the results of the roundtable SynBERC. There will be a Flowers Because the workshop was held in discussion was the establishment of a Consortium session at the 2015 SynBERC the Flowers Building at Imperial, the working group to develop a roadmap for meeting, in Berkeley, USA. consortium was called the Flowers synthetic biology for the UK – this was Consortium and was established by a SYNTHETIC BIOLOGY HUB encompassing: CSynBI The Flowers Consortium SynbiCITE The Foundry Frontiers Engineering

Synthetic biology at Imperial College London continues to grow and CSynBI is now a leading centre of excellence with a network of research teams and innovation and knowledge centres. CSynBI is proud of the scale of its activities, which range from education to world-leading research to industrial applications. It influences strategy and spearheads engineering in synthetic biology. It is leading the way in automating the production of interchangeable genetic elements. Development of these elements is critical if we are to scale up synthetic biology processes such that we can make a real impact in the big challenges facing society. CSYNBI.. A programme of research, training, development and dissemination has, PRINCIPLE INVESTIGATORS.. The Centre for Synthetic Biology and through upstream involvement from IN THE CENTRE.. Innovation (CSynBI) is the academic arm the very outset of CSynBI, enhanced of the Hub, which is led by Professors capabilities to understand the ways that Professor Richard Kitney, Richard Kitney and Paul Freemont. developments in synthetic biology impact Co-Director: BioLogic, biosensors, It specialises in the research and and shape the world around us, and modelling development of foundational tools continues to facilitate the development Professor Paul Freemont, for synthetic biology and the use of of informed dialogue and an appropriate Co-Director: Biosensors, part these tools in new applications to solve regulatory and policy regime. CSynBI also characterisation problems for example in industry and works with key social scientists from the Professor Nik Rose, healthcare. CSynBI is committed to on responsible Kings College London: Ethical, legal responsible research and innovation research and innovation. and societal issues (RRI) and is therefore comprised of scientists and engineers at Imperial Academics in CSynBI were the first Dr Tom Ellis: College London and societal and ethical to design and implement synthetic DNA assembly, gene networks and issue researchers from the Department biology courses in the UK (and possibly modules of Social Science, Health and Medicine at in Europe). Consequently, researchers Dr Geoff Baldwin: King’s College London. at CSynBI play a large role in teaching Directed protein evolution synthetic biology at Imperial College Dr John Heap: The scientific research goals of CSynBI through undergraduate and postgraduate are to establish an engineering framework Development of foundational courses. Synthetic Biology is a technical biological technologies for the design and optimisation of new option for year 3 BEng and MEng biological parts, devices and systems, undergraduate students following both Dr Karen Polizzi: Biosensors for bioprocessing and, in tandem, to apply synthetic the Electrical and Mechanical pathways of biology to develop a wide range of the Biomedical Engineering programmes. Dr Clare Marris, novel biotechnologies. Led by Professor It is also available to students working Kings College London: Ethical, legal Nik Rose from Kings College London, towards a BSc in Biochemistry or Biology. and societal issues CSynBI is also addressing issues of At the postgraduate level CSynBI is proud Dr Guy-Bart Stan: public engagement and trust, as well as to offer an MRes in Systems and Synthetic Biomodelling analysis and control engaging with the central concerns of Biology and many PhD opportunities. policy and regulation in this novel and rapidly developing area. www.imperial.ac.uk/syntheticbiology THE FLOWERS CONSORTIUM.. Now half way through, the Flowers Project has achieved a number of The Flowers Consortium is made up important goals. of representatives from the Universities of Cambridge, Newcastle, Edinburgh The community now has the ability to and Kings College London. Professor Nik undertake multi-institutional research Rose and Dr Clare Marris at Kings College collaboration across the Flowers London, and Drs Jane Calvert, Emma Frow Consortium, enabling the cohesive and Professor Joyce Tait at the University development of platform technologies of Edinburgh, specialise in researching and the integration of tools and the ethical and societal issues associated methodologies which will impact with synthetic biology as part of the the ability to undertake systematic Flowers Consortium’s mission. design.

The fundamental aim of the Flowers The definition and implementation Consortium is to create a prototype of key emergent metrology concepts end-to-end synthetic biology systematic and standards (DICOM-SB and design platform that will be able to SBOL) and their integration into an interface with a range of existing and enabling IT infrastructure (SynBIS) - emerging design technologies and deliver built to enable efficient information usable chassis/constructs that can be exchange and extraction. This used in the design-build-test-learn cycle. facilitates knowledge aggregation and consolidation.

www.synbiuk.org

SYNBICITE.. To be an effective vehicle for the LEAP: SynbiCITE supports and support of small to medium sized participates in LEAP, a programme SynbiCITE is the UK’s national centre UK companies including start-ups in designed to develop early career for the commercialisation of synthetic synthetic biology researchers who aspire to be leaders biology. It is a resource of interacting in synthetic biology. partners from academia and business To actively engage in open dialogue brought together to accelerate growth with the public and other stakeholders 3 Day MBA: SynbiCITE offers this of high value industries. focusing on the risks and benefits of intensive programme to train and It is part of the core activity of synthetic synthetic biology technologies teach participants how to build a synthetic biology start-up from biology and is now becoming a major To achieve this SynbiCITE offers a scratch. component in the industrial translation variety of programmes, services and of the platform technology which expertise. is being developed by the Flowers BUSINESS DEVELOPMENT.. Consortium. SynbiCITE currently TRAINING AND SKILLS DEVELOPMENT.. SynbiCITE supports and develops comprises 19 academic institutions and synthetic biology based businesses by 56 industrial partners and associated SynbiCITE offers innovation offering funding, business incubation, organisations, ranging from small spin programmes and network training business support services and specialist out companies to large multinationals opportunities in business development, laboratory space and facilities. including GSK, Shell and as and professional well as the Northern Ireland, Scottish advancement. SERVICES.. and Welsh Regional Governments, plus Key training events include: the Authority. SynbiCITE offers problem-solution Lean Launchpad: an eleven week brokerage and can link members in its AIMS.. programme which redefines the network to specialists in synthetic biology SynbiCITE’s aims are three-fold: traditional business model and to assist with specific projects. provides participants with a unique To be a translation engine which www.synbicite.com opportunity to iterate their product translates university and industry based on extensive customer based research in synthetic biology consultation. into industrial process and products THE FOUNDRY.. execution of all the most common gene/ quantitative analyses. Also, to allow genomic assemblies and genomic editing the Foundry to function efficiently, a Designing, constructing and testing protocols. Automation of synthetic Laboratory Information Management DNA is a crucial element in the systematic biology techniques will greatly increase System (LIMS) has been developed. The design of biological devices. the robustness of the processes and ability to track the progress of various These devices are made from harmless reproducibility of data collected. The net assets through the process and directly cells, such as non-pathogenic yeast. result will be an increase in the size of link the data acquired is of critical Manmade yeast genes could then be used the experimental space covered by the importance. The LIMS provides an audit to create vaccines or even turn agricultural investigator, and greater quality of the trail for the synthesis, assembly and waste into biofuel. data and models produced. verification of the various components: DNA, parts, devices, circuits, modules The strength of the modular design of Imperial recently received £3.5M and systems. In addition, the database the platform is its ubiquity and the range (£4.5M total) to establish a ‘DNA and the ability to track the workflow of analytical techniques it can apply to Synthesis and Construction Foundry’. enables more efficient scientific characterisation and verification. Building interchangeable pieces of DNA, management of complex projects. The the building blocks of synthetic biology, Modularity also allows the exploitation Foundry has an automated sample is time consuming and expensive. of both conventional and acoustic management store to provide a freezer CSynBI and SynbiCITE have designed a liquid handling. The platforms have storage system for secure sample suite of automated platforms to perform been specifically designed to allow management of plates and tubes. gene assembly and verification of those the assembly and characterisation in The establishment of the DNA Synthesis assemblies. The platforms have a modular multiple chassis, including E.coli and and Construction Foundry complements design supplying the flexibility to perform other bacterial stains, but also yeast SynbiCITE, which aims to bridge the gap a range of different assembly protocols and mammalian cells. A diverse range between academia and industry to speed and cope with the development of new of cellular, biochemical and biophysical up developments in new synthetic biology techniques. Modularity also allows analytical tools capable of characterising technologies. the interchange of different robotic and DNA, RNA, protein and metabolite are analytical equipment, again to provide integrated with the platform to provide www.imperial.ac.uk/syntheticbiology/ maximum flexibility. The resulting a complete spectrum of qualitative and synbiohub/foundry automation allows the high-throughput Frontiers Engineering Frontiers Engineering Scaling up synthetic biology Scaling up synthetic biology

FRONTIERS ENGINEERING.. two consumer areas (therapeutics and The first is healthcare, specifically the chemicals manufacturing). manufacture of medicinal compounds and In 2013, Imperial College London was therapeutic proteins. These are already To develop these future biofactories, awarded £5 million to investigate how to largely made using biological systems, the Synthetic Biology Hub at Imperial is scale up synthetic biology. but the existing processes are expensive inventing new, generalised technologies and complicated. Also, in the future, it In order to realise the potential to underpin the new manufacturing would be more efficient to make these of synthetic biology in terms of processes. It is producing new biologically medicines as and when they are needed revolutionising the way industry makes a based sensors in order to be able to (point-of-care manufacture). The Hub’s host of consumer products from materials monitor the production processes as goals are to make simpler, more cost and energy to food and medicine, it is they occur to ensure product quality effective, point-of-care manufacturing necessary to find ways of translating (and allow intervention if necessary). systems using a combination of the above laboratory discoveries into operating The Hub is also researching new, mentioned platform technologies: enzyme industrial production processes. The more robust production cells that can microreactors, specialised cells, and challenge is to transition from existing tolerate the high levels of compounds biosensors. factories into the factories of the future. they make and new microreactors and/ Today many consumer products or compartmentalisation strategies for The second target is to produce bulk are made from fossil resources using using enzymes when whole cells are chemicals without the need for petroleum synthetic chemistry techniques. In the not required. Because the transition inputs. To do this, manufacturing future it will be necessary to reduce will not happen overnight, the Hub is techniques are being adjusted for dependence on petroleum products and developing intermediate production renewable inputs (such as biomass) move to renewable resources. At the same methods that combine biological and and new processed are being developed time, the advent of synthetic biology chemical catalysts. This requires solvents that use biology and/or environmentally techniques for rapidly tailoring biological that are less toxic to proteins and cells friendly chemistry to do the conversions. and proteins that are engineered to be systems for manufacturing purposes will Synthetic biology has never been more robust in the presence of chemicals. allow the transition away from synthetic attempted on such a large scale. The In order to develop processes that are chemistry to more environmentally challenge is to adapt the current parts, economical and efficient (minimal energy friendly production mechanisms using devices, and systems to operate at the and water usage), the Hub is creating non-pathogenic microorganisms. The required level. The overall outcome will be computer models to compare alternatives. synthetic biology Hub at Imperial College novel, cost effective, energy efficient, and The most promising processes will London is tackling the question of how sustainable routes to therapeutics and be implemented in the factories of to undergo this transition smoothly chemicals. by working with industrial partners, SynbiCITE’s industrial partners. www.imperial.ac.uk/syntheticbiology/ GlaxoSmithKline, Lonza Biologics and Two challenge areas have been selected synbiohub/frontiers Shell, on real-world applications in in which to test the new technologies. IGEM

iGEM is an extremely important annual international student competition in synthetic biology, attracting teams from the world’s leading universities. Since Imperial entered its first iGEM team in 2006, it has consistently entered talented teams with innovative projects ranging from water purification solutions, to drug delivery mechanisms, to soil erosion preventions. Imperial is proud to have maintained its enviable position as the most successful UK, and probably international, university in the competition. This is despite the competition increasing in size from 32 teams in 2006 to 220 teams in 2014. In both 2006 and 2014 Imperial placed second overall and each year won a gold medal and a raft of prizes. In total Imperial has achieved 8 gold medals and 17 major prizes and now has more than 60 alumniGEM. www.imperial.ac.uk/syntheticbiology/igem www.igem.org iGEM 2014 team with George Freeman MP, Parliamentary Under Secretary of State for Life Sciences

Project I.coli Prizes awarded Position/medals awarded 2nd overall Best documentation 2006 Total number of teams in competition 32 Best measurement and part characterisation

Project The Infector Detector Position/medals awarded Gold Total number of teams in competition 54 2007

Project Designer genes - Biofabricator subtilis Prizes awarded Position/medals awarded Gold Best manufacturing project 2008 Total number of teams in competition 84 Best natural new biobrick part

Project The Encapsulator Prizes awarded Position/medals awarded Gold Finalist Best human practices advance Total number of teams in competition 112 Best manufacturing 2009

Project Parasight Prizes awarded Position/medals awarded Gold Finalist, Best human practices advance 2010 Total number of teams in competition 130 Best wiki, iGEMers Prize

Project Auxin Prizes awarded Position/medals awarded 2nd overall European World finalist, Best Poster, Grand prize Winner, Gold winner (Europe), Best wiki (Europe), Safety Total number of teams in competition 165 commendation (Europe), iGEMers prize 2011

Project Plasticity Prizes awarded Position/medals awarded 3rd overall, Gold Best manufacturing project 2013 Total number of teams in competition 215 Best new engineered BioBrick part

Project Aqualose Prizes awarded Position/medals awarded 2nd overall, Gold Best part collection Total number of teams in competition 220 Best manufacturing project Policy and Practices Commendation 2014 RESEARCH CASE STUDIES AND GATE CIRCUIT DESIGN

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DEVELOPMENT OF.. molecules produced by bacteria, while means that, for example, their response its implementation in a cell-free platform times are very much longer – but IN VITRO BIOSENSORS FOR.. provides improved biosafety when compatible with the response times of THE DETECTION OF.. compared to whole-cell systems. After biological systems. We have recently demonstrating that these biosensors are completed the design and testing of a INFECTIOUS BACTERIA.. able to detect endogenous signalling more complex digital device called a half- Cell-free synthetic biology has gained molecules from cultured P. aeruginosa, we adder. This comprises multiple gates that increased popularity in recent years as an have now progressed to testing clinical work stably in unison. Immediate areas of alternative platform to live cells, enabling samples from cystic fibrosis patients with application are in advanced biosensors. In the study of biological systems in an P.aeruginosa infections. Ultimately the the longer term, there is the potential to environment of reduced complexity. We aim is to provide an improved detection development biologically-based devices have developed biosensors in cell-free method that can aid in the diagnosis and for information processing and control, systems for the detection of pathogenic monitoring of bacterial infections. e.g. in the application of human-imposed bacteria, with a focus on Pseudomonas intra-cellular control. aeruginosa – an opportunistic pathogen LOGIC GATES.. Sc2.0.. that can cause persistent infections in Logic gates (e.g. AND, OR and NAND) are humans with compromised immune the basis of all electronic digital devices CSynBI is leading the UK’s contribution systems. It is a particular concern for from mobile phones, to microprocessors, to the ground breaking Sc2.0 project cystic fibrosis patients, as it is able to to computers. Similarly, the development to synthesise a new version of colonise the lung and is resistant to of biologically based logic gates and Saccharomyces cerevisiae. This project antibiotic treatment. logical devices has major potential in will result in the construction of a To detect the presence of these bacteria, terms of information processing and eukaryotic genome. This will be the first we utilised their natural cell-to-cell control. We have designed and developed time that this has been achieved and once communication mechanism, known a range of modular, stable biological complete will provide synthetic biologists as quorum sensing (QS). Biosensors logic gates. The gates are conceptually with a tool to make valuable products have been constructed using the native similar to their electronic equivalents, but such as chemicals, vaccines or biofuels response elements of bacteria and different in operation. They are designed using synthetic genes and genomes. coupled to a detectable output. This to work in the biological domain, which enables the detection of QS signalling TIMELINE 2006 2008 2009

Imperial College Synthetic Biology CSynBI offers a final year Imperial College London and Kings Laboratory founded. option in Synthetic Biology to College London launch CSynBI with undergraduates studying for a just 4 Principle investigators and 6 First Imperial team enters the iGEM BSc in Biochemistry or Biology students. competition. or a BEng or MEng in Biomedical Engineering, representing the first CSynBI hosts its first panel debate: ‘Creating the organisms 2007 undergraduate synthetic biology programme in the UK. that evolution forgot?’. Held at the London School of Economics Research develops – research Professor Kitney chairs a Royal the event was chaired by Quentin student numbers increase. Academy of Engineering Inquiry Cooper, presenter of the most into synthetic biology to define the listened to science series in the UK, term ‘synthetic biology’, review The Material World on BBC Radio 4. the state of the field and consider potential future developments and 2010 their likely technological, economic and societal impact. CSynBI hosts a two day workshop: ‘Synthetic biology and open source: normative of biology’ at the London School of Economics. 2011 2013 2015

Creation of the Flowers consortium; Launch of SynbiCITE. CSynBI current population. 10 a collaboration between Imperial principle investigators, 60 other College London, University Professor Freemont delivers the researchers, 20 associated groups/ of Edinburgh, University of Royal Institution Lecture. centres at Imperial. Cambridge, CSynBI invited to join SynBERC, and Kings College London to Professor Kitney delivers Annual a major U.S. research programme develop foundational technologies. City and Fellowship Lecture. to make biology safer and easier CSynBI holds a workshop on the to engineer. The first organisation SynbiCITE brings Lean LaunchPad historical, social and philosophical outside of the US to do so. for Synthetic Biology to the UK for aspects of modelling and their the first time. CSynBI hosts a workshop on implications for synthetic biology the containment and release of Imperial hosts SynBioBeta London at the London School of Economics. engineered micro-organisms at 2015. Professors Kitney and Freemont are Kings College London. Professor Freemont to deliver the invited to join a working group to Royal Society of Medicine Ellison- develop a Roadmap for Synthetic 2014 Cliffe Lecture 2015. Biology for the UK. Professor Kitney delivers IET 2012 Kelvin Lecture.

CSynBI hosts a workshop on Publication of the influential synthetic biology and biosecurity at ‘Roadmap for Synthetic Biology for Kings College London. the UK’. METRICS 200 60 60 MRES ALUMNI

200 undergraduates have successfully completed the synthetic biology technical options of the Bioengineering BEng and MEng programmes. ACADEMIC 40 COLLABORATORS 53 40 PHD ALUMNI SynBio @Imperial

PUBLICATIONS GRANT INCOME over 150 since over £30M since 2006 2008 Centre for Synthetic Biology and Innovation Imperial College London South London SW7 2AZ Tel: +44 (0)20 7594 3649

imperial.ac.uk/syntheticbiology