Award details

SynthSys-Mammalian: Edinburgh Mammalian Synthetic Biology Research Centre

Reference	BB/M018040/1
Principal Investigator / Supervisor	Professor Susan Rosser
Co-Investigators / Co-Supervisors	Professor Adrian Bird, Professor Yizhi Cai, Professor Jane Calvert, Professor Vincent Danos, Professor Jamie Davies, Professor William Charles Earnshaw, Professor Alistair Elfick, Professor Charles ffrench-Constant, Dr Emma Frow, Professor Andrew Millar, Dr Nacho Molina, Professor Teuta Pilizota, Professor Steven Pollard, Professor Peter Swain, Professor Joyce Tait
Institution	University of Edinburgh
Department	Sch of Biological Sciences
Funding type	Research
Value (£)	11,379,882
Status	Completed
Type	Research Grant
Start date	14/11/2014
End date	31/03/2022
Duration	89 months

Abstract

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.

Summary

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.

Impact Summary

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.

Committee	Research Committee D (Molecules, cells and industrial biotechnology)
Research Topics	Synthetic Biology, Technology and Methods Development
Research Priority	X – Research Priority information not available
Research Initiative	Synthetic Biology Research Centres (SBRC) [2013-2014]
Funding Scheme	X – not Funded via a specific Funding Scheme

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