Award details

Edinburgh Genome Foundry

Reference	BB/M00029X/1
Principal Investigator / Supervisor	Professor Susan Rosser
Co-Investigators / Co-Supervisors	Professor Yizhi Cai
Institution	University of Edinburgh
Department	Sch of Biological Sciences
Funding type	Research
Value (£)	2,000,295
Status	Completed
Type	Research Grant
Start date	16/09/2014
End date	15/09/2015
Duration	12 months

Abstract

This project aims to set up a genome foundry to enable the design and synthesis of large fragments of DNA based on the automation of technologies developed as part of the Sc 2.0 project (http://syntheticyeast.org/). Our vision is that the Edinburgh Genome Foundry will provide design, construction and validation of large gene constructs (up to 1Mbp) for academic and industrial application, and it will serve as an enabling technology platform for a wide range of fundamental and biotechnology related research in the UK and beyond. Through Edinburgh's deep involvement in the Sc2.0 project, we have developed and mastered the end-to-end synthesis methods for large DNA segments up to the chromosome scale. To scale up the synthesis throughput, lower the cost and shorten the turn around time, Edinburgh Genome Foundry will focus on automating DNA synthesis and assembly pipelines. All the automation machines are connected and the design is completely modular so that the foundry can be easily expanded in the future. We will be producing oligonucleotides in house. The reaction set up will be handled by liquid handlers and two acoustic dispensers that can effectively transfer nl droplet from a source plate to a destination plate using sound energy, which saves significantly on expensive conductive tips and avoids cross contaminations between samples. The ability to accurately transfer liquid droplets at nl scale will enable us to downscale reaction volumes from ul to nl scale. In addition we are planning to innovate by using acoustic dispensers to plate bacterial transformation cultures for single colony isolation, which is known to be very low throughput and difficult to automate.

Summary

Our vision is to establish a Genome Foundry at the University of Edinburgh that will provide end-to-end design, construction and validation of large gene constructs (up to 1Mbp) for academic and industrial applications. The Foundry will also provide a valuable test bed for novel processes and systems so we can realise a vision of full automation of the DNA synthesis process for next generation of synthetic biology. Our vision is that the design, construction and testing of up to chromosomal size synthetic constructs will become a routine part of lab life and will be available at a similar low cost to that of DNA sequencing today. However, there is much to be done to realise that goal as we need to find ways to reduce the labour-intensive and error-prone nature of the current synthetic process and better automate the workflow. The synthetic biology community needs the ability to assemble very large strands of DNA enabling the interrogation at a fundamental level of how biology works and has evolved, expression of large complex engineered genetic circuits and metabolic pathways. The Genome Foundry at Edinburgh will address these challenges: 1) It will provide a core national capability to design, build and validate large DNA constructs, generated using current state-of-the-art technologies, to support the next phase of synthetic biology. 2) It will act as a test bed for the development of new processes and systems, generated internally and externally, to facilitate the transformation of DNA synthesis to a fully automated process.

Impact Summary

Edinburgh Genome Foundry will provide end-to-end design, construction and validation of large gene constructs (up to 1Mbp) for academic and industrial applications. The novel tool development proposed will enable the University of Edinburgh and the UK to maintain a position of leadership in SB. This in turn will help to attract and retain high quality researchers in the UK. The ability to efficiently construct increasingly large, complex genetic circuits and metabolic pathways opens the opportunity e.g. to program stem cell differentiation, detect multiple changes in cancer cells, build synthetic viruses to generate vaccines or act as delivery vectors, engineer cell factories for novel drugs or "greener" chemicals and biofuels - all of which will contribute to a new revolutionary bioeconomy. We have a broad range of good working relationships with local (e.g. Ingenza, Genabler,) and international businesses (e.g. Life Technologies, Selex ES) with an interest in DNA synthesis, synthetic biology and its application and will build on these collaborations through the Foundry. Importantly, our existing and developing relationships with industry partners will ensure we work alongside, rather than compete with, commercial providers while safeguarding our potential to develop Intellectual Property addressing new markets. Currently there are no companies providing DNA synthesis of sequences at this scale so we are not competing with industry in this arena rather we are working with industry and innovating in an area which will be of great commercial interest in the future. We are working closely with Life Technologies and are in the process of negotiating a strategic partnership with them in this space. The Foundry will be established and grown in stages. Stage 1 (12-18 months): The Foundry will be hosted by the Centre for Synthetic and Systems Biology (SynthSys) and will benefit from interim Marketing, Business Development and Facility Management support from Dr Liz Fletcher (Centre Manager) and Lorraine Kerr (Facility Manager). Stage 2 (18-36 months): The Foundry will begin to operate on a fee-for-service basis and hire a full time Facility Manager to drive new business and build the Foundry towards sustainability. Stage 3 (beyond 36 months): Close working with Edinburgh's Research & Innovations, the University's commercialization support, we allow periodic review of the commercial potential of the Foundry. A business decision will be made as to whether the Foundry's longer-term sustainability would be best served by spinning out as a commercial venture (being mindful of the potential conflict with commercial providers) or to continue to be hosted by the School, akin to the status of Edinburgh Genomics. Societal and stakeholder engagement is considered vital to the continued emergence of SB technologies as product. We wholeheartedly recognize the importance of open communication of our research to as wide an audience as possible; both through the scientific and non-scientific press, through various media outlets including the internet and through participation at specialist and general science conferences and festivals.

Committee	Not funded via Committee
Research Topics	Microbiology, Synthetic Biology
Research Priority	X – Research Priority information not available
Research Initiative	DNA Synthesis (DNASyn) [2014]
Funding Scheme	X – not Funded via a specific Funding Scheme

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