Building national hardware and software infrastructure for UK DNA Foundries

To date, the BBSRC has invested over £50M towards establishing Synthetic Biology Research Centres (SBRCs) and building DNA synthesis facilities in the UK. This application seeks to build on this investment through establishing a collaboration between Edinburgh, Cambridge and TGAC to develop software infrastructure to improve efficiency and automation and to consolidate and further enhance the services offered at the national DNA foundries based in Edinburgh and Norwich. The software infrastructure will be developed by teams at Edinburgh, TGAC and Cambridge with well-established track records in high quality software engineering. The software will be made freely available under an open source license to all members of the SB community via software repositories. This proposal also complements EPSRC-funded SB work at Edinburgh and Cambridge as part of the nationwide Flowers Consortium thus providing a natural route to dissemination.

The infrastructure proposed will significantly enhance the Edinburgh and TGAC DNA synthesis facilities, and the implementation of the software infrastructure will establish a new collaboration between three strong software teams across the UK, with the intention that these collaborations will grow with time. Both hardware and software infrastructure will enhance the speed and efficiency with which DNA can be designed, synthesized, assembled and verified, increasing the capability to generate synthetic DNA sequences. Finally, we will also implement sequence screening protocols to safeguard synthetic biotechnology.

One of the enabling platform technologies in Synthetic Biology (SB) is the de novo DNA synthesis up to chromosome size. To drive down the currently prohibitive costs of DNA synthesis requires streamlining and therefore automating, where possible, the various steps of the synthesis processes. Our vision is that UK DNA synthesis facilities will be able to implement innovative software to support their state-of-the-art hardware, thus to enable the end-to-end design, construction and validation of large DNA constructs for academic and industrial application supporting a wide range of fundamental and biotechnology related research in the UK and beyond. We request funding to expand UK DNA synthesis facilities based in Edinburgh and TGAC by acquiring additional automated instruments such as an automated -80c freezer to streamline the sample storage and an benchtop nextgen sequencer to verify the synthesized DNA sequences. We request support to adapt open source LIMS system MISO for DNA synthesis purpose. Various CAD and CAM tools will be integrated into a cohesive package to boost the productivity of the UK DNA foundries. Finally, we will implement sequence screening protocol by collaborating with industrial DNA synthesis consortium ICSG to prevent the dual use of technology.

This application seeks to build on this investment through establishing a collaboration between Edinburgh, Cambridge and TGAC to develop software infrastructure to improve efficiency and automation and to consolidate and further enhance the services offered at the national DNA foundries based in Edinburgh and Norwich. The foundries will provide end to end design, construction and validation of large gene constructs for academic and industrial applications. Both hardware and software infrastructure will enhance the speed and efficiency with which DNA can be designed, synthesized, assembled and verified, increasing the capability to generate synthetic DNA sequences enabling 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 data infrastructure framework will support all aspects required to run a state-of-the-art DNA foundry, including tracking of samples and automation through a LIMS as well as sophisticated computer assisted design (CAD) and computer assisted manufacture (CAM) tools.
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, Autodesk) 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 both Life Technologies and Autodesk are in the process of negotiating a strategic partnership with them in this space.
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.