Software systems for Imperial College DNA Foundry (LIMS/automation/interfaces)

Lead Research Organisation: Imperial College London
Department Name: Dept of Bioengineering

Abstract

Synthetic biology has the tremendous potential for enabling the design and implementation of sophisticated biochemical mechanisms for sensing, computing, control, production, and activation. This approach is anticipated to lead to many breakthrough applications in biotherapeutics, bioremediation, biomaterials, and in vivo-sensing and activation and self-assembly. The hardware available to exploit synthetic biology has evolved to deliver the many protocols for synthesizing DNA and verifying its assembly. Advances in liquid handling, automation, miniaturization, microfluidics and spectroscopy have collectively combined to make possible the rapid construction of synthetic genes, engineered pathways and synthetic genomes. The initial capital funding of this technology at the Centres of DNA Synthesis (The Foundries) has made possible the development of automated workstations organized to synthesize DNA components and assemblies designed to meet defined biofunctional performance parameters. As a direct consequence of the automation of DNA synthesis and assembly there has been a massive increase in throughput, size and complexity of experimental space covered. The research challenge now faced is the lack of an integrated suite of software tools to support DNA synthesis at the Foundry scale. This is part logistical, in the management of the process and data, and part statistical in the interpretation and modeling of the massive amounts of data generated by the Foundry. Similar to the automation of DNA sequencing, automation of synthetic biology in the Foundry will result in the generation and processing of huge amounts of data.
The aims of this proposal:

- Maximize the efficiencies of the Foundry by developing an open source operating system to support an integrated engineering design workflow allowing seamless inter-tool communication for hardware and software.
- Develop a 'Knowledge Centre' capable of providing storage, processing, analysis and predictive modeling of the data coming from DNA design, sequencing, characterization and process metrics generated by the Foundry.
- Build the computational infrastructure to comply with the International Gene Synthesis Consortium (IGSC) to prevent the misuse of synthetic genes. Sequences of DNA synthesized will be screened and users vetted to ensure vigilance and biosecurity of the Foundry.

Technical Summary

The operating system will establish a platform to support a suite of synthetic biology software tools, allowing the seamless integration of hardware, management and analysis of the data generated by the Foundry.
The operating system will have two main components:

A suite of interchangeable technologies and software tools serving the needs of the Foundry. These will range from CAD/CAM tools to design the various DNA components, device control linking hardware and software, automated execution of experimental and process workflows, and sample and inventory tracking.

A data management system 'Knowledge Centre' for the storage, processing, analysis, and predictive modeling of data generated by the Foundry. The data, which comes from a range of diverse sources such as DNA design, sequencing, functional data from the characterization process and the Laboratory Information Management System (LIMS), will be an analyzed to uncover meaningful patterns in the high-throughput data generated by the Foundry. The data will be explored using comprehensive set of traditional and advanced statistical algorithms. In the rapidly advancing field of synthetic biology, the ability to conduct sophisticated analyses on large volumes of data and visualize the significance adds a vital new dimension.

Planned Impact

The British Government clearly recognises the importance of synthetic biology in relation to the UK's economic development. The field has been identified as one of the Government's "8 Great Technologies" and this has been endorsed by The World Economic Forum. Synthetic biology is a classic example of a knowledge-based industrial area, which is leveraging the UKs science and engineering base. Effective industrial translation is, therefore, a key element in the development of new processes and industries. Standardisation is central to industrial translation and industrial processes. Consequently, an important component of this process in synthetic biology is the handling, assembly and verification of DNA components of various lengths - and in the context of various cellular hosts. The proposal, building on the funding already in place for the foundry, is based on the development of an operating system of integrated software tools to complete the design, build, test, report and learn cycle paradigm. The impact of this will be to create a foundry capable of providing automated end-to-end design, construction and validation of large gene constructs for academia and industry. The Foundries ability to effectively translate academic research into industrial products and services is critically dependent on the availability and integration of software to manage and engineer the design process. Modern process development and production is heavily dependent software design tools to perform Design of Experiments (DoE), Quality by Design (QbD) and Six-sigma, without access to these tools it will be increasing difficult to interact with any commercial partners. Investment in the development and integration of a suite of software tools for DNA synthesis aligns with the Foundry's mission to provide a standardized framework for DNA synthesis, gene and genome assembly and assembly verification. It is envisioned that an integrated suite of software tools for DNA synthesis developed, and the open source operating structure, will interface with other software and hardware. The creation of a standardized operating system for DNA synthesis and assembly has the potential to encourage commercial software developers and hardware companies to develop tools which will interface with the operating system. The integration of industry-standard hardware and open source software, when fully implemented and tested it will be possible to replicate the operating system at multiple foundries around the UK.
In summary, we believe the operating system we are proposing, is strategically important for synthetic biology research, its translation and the development of UK industry in the field. Our strategy is to create and implement an operating system to serve the Foundry, which will enable the UK to have significant capability and expertise in DNA synthesis, assembly and verification now and in the longer term.

Publications

10 25 50
 
Description The most significant achievement of this award was the development and implementation of an operating system capable of programming and integrating the London DNA Foundry hardware with the flexibility to handle a rapidly expanding number of synthetic biology protocols. The delivery of this unique operating system combines a design & build software interface (AMOS), with visual analytics and a laboratory information management system (LIMS). The web-based operating system, maximises user experience, providing seamless ease of access to third-party software tools, and automated access and visualisation of data.
The operation of the London DNA Foundry represents unique public-private collaborative effort to accelerate and translate academic research into commercial products and services. Funding from the award was matched with contributions from industrial partners providing a significant return on investment to the taxpayer.
Exploitation Route The London DNA Foundry plans to function as a core facility for the synthetic biology community. With a growing number of academic collaborators and industrial customers funding activities the foundry, it is hoped that the Foundry will become economically sustainable in the near future. This outcome would ensure that the funders initial investment is extended beyond the lifetime of the grant.
The key functionality of the operating system is open sourced, and freely available to developers of synthetic biology tools to use. The London DNA Foundry is active seeking collaborations to disseminate the lessons learnt in the development of the software to operate the Foundry.
Sectors Education,Manufacturing, including Industrial Biotechology,Other

 
Description The purpose of the LIMS grant was to develop software systems associated with the Imperial College DNA foundry. Since the start of the grant, very significant progress has been made in the development of software systems - particularly in relation to the development of sophisticated workflow associated with synthetic biology. Advances in liquid handling, automation and miniaturisation has developed into the concept and implementation of an advanced biofoundry, called the London Biofoundry. Associated with this has been the development of advanced workflow, which is based on a web-based information system called SynBIS and its underlying data model. This has been incorporated into a workflow that starts with detailed characterisation of bio parts for genetic constructs (including detailed descriptions of experimental procedures/protocols and meta data). How have the findings from this award contributed to any non-academic impacts? The development of the LIMS workflow has enabled us to design experiments much more accurately, resulting in much higher levels of reliability and reproducibility (in terms of gene circuits and devices). A key aspect of this has been the development of a Bio Design knowledge centre that comprises the components of the Design Build Test and Learn (DBTL) Paradigm. Specifically, in relation to Bio Design and the contribution to companies, it has been possible to develop a workflow which incorporates Design of Experiments (DoE). Following the basic design, the next stage is optimisation. A given gene circuit design, may comprise a number of components, which can be of different types (e.g. multiple constitutive promoters of different strengths) and in different orders within the gene circuit (see example below). How have your findings been used? The impact which has been achieved is that information system (LIMS) and the DoE software allows statistical sampling of the design space. Hence, for example, for gene circuit that may comprise 1 constitutive promoter, 3 RBS', 3 coding sequences and a terminator, there is the possibility of 810 component configurations. With the use of the LIMS and DoE, this can be reduced to 88 possible configurations- which for industrial yields can make a two order of magnitude difference. The ability to use the LIMS to access a range of component databases across the network (national and international), coupled to the use of DoE has had a significant impact in terms of the companies that we work with. Currently, we are working with over 20 companies (start-ups, SMEs and large companies) on Bio Design, utilising our Knowledge Centre, LIMS, DoE and the underlying information system. Specific examples of companies include: LabGenius (development of advanced proteins); Puraffinity (advanced filtration systems to remove PFOE - a highly toxic chemical); Prokarium (a biopharmaceutical company focused on developing vaccines and immunotherapy solutions based in synthetic biology.
First Year Of Impact 2015
Sector Digital/Communication/Information Technologies (including Software),Environment,Healthcare,Manufacturing, including Industrial Biotechology
Impact Types Economic

 
Description UK Synthetic Biology Strategic Plan 2016 - Biodesign for the Bioeconomy.
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact Minister for Life Sciences George Freeman MP visited SynbiCITE at Imperial College London, the UK innovation and knowledge centre for synthetic biology, on 24th February 2016 to announce the release of the UK Synthetic Biology Strategic Plan 2016 - Biodesign for the Bioeconomy. This strategic plan, published by the Synthetic Biology Leadership Council (SBLC), aims to accelerate the commercialisation of synthetic biology products and services with clear public benefit, building upon the strength of the UK research base. It focuses on five key areas of strategic importance: Accelerating industrialisation and commercialisation Maximising the capability of the innovation pipeline Building an expert workforce Developing a supportive business environment, and Building value from national and international partnerships. It builds on the recommendations made in the Synthetic Biology Roadmap for the UK, which was first published by Innovate UK in 2012. The roadmap led directly to major funding and policy activities, including the establishment of new synthetic biology research centres, the Innovation and Knowledge Centre at SynbiCITE, DNA synthesis facilities, training centres and a seed fund for innovative companies. In addition, the Synthetic Biology Leadership Council (SBLC) was founded to manage the continued growth of this field. During 2015, the Synthetic Biology Leadership Council (SBLC) consulted a broad cross-section of businesses and the research community to develop this new strategic plan, building upon the successes of the 2012 roadmap.
URL https://connect.innovateuk.org/documents/2826135/31405930/BioDesign+for+the+Bioeconomy+2016+DIGITAL+...
 
Description Francis Crick/Imperial College Translational Visit 
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 Professional Practitioners
Results and Impact The Crick's Translational Unit were shown how a national accelerator programme works, and focusses on a single area. They were also given a tour and a presentation on our Lean Canvas Model and Programme. This was part of a wider Imperial College visit.
Year(s) Of Engagement Activity 2017
 
Description Global Biofoundry meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A meeting was held at Imperial College London on June 21st/22nd 2018, which gathered fifteen[1]of the leading synthetic biology biofoundries from around the world to discuss current activities and exchange information on key capabilities and projects being developed by these groups.
The meeting explored opportunities for collaboration and coordination in areas for global development including standards, software, metrology, automation, and industrial translation. Delegates unanimously indicated a commitment to sharing pre-competitive knowledge and expertise that would collectively benefit the synthetic biology and broader biotechnology communities worldwide.
Interest in developing common protocols and standards, as well as standardised legal tools, to reduce the transaction costs of sharing were among the highlights of the two-day interactive meeting. Other areas of discussion included collective engagement with industry, governments, and other relevant organisations to achieve joint objectives, break down barriers to sharing and leverage interactive opportunities for growth. There was a general commitment to continue to explore the possibility of establishing a global alliance of synthetic biology biofoundries and to work together to define and agree on an operating model. As a starting point, an annual meeting was proposed as was the establishment of small working groups to develop specific areas for global development.
[1]1DOE Agile Biofoundry (US); DAMP, Boston University (US); SIAT Shenzhen (China) Foundry; Concordia University (Canada); Earlham Institute (UK); London DNA Foundry Imperial College (UK); Kobe University (Japan); Macquarie University (Australia); SynCTI NUS (Singapore); Novo Nordisk Foundation Center for Biosustainability DTU (Denmark); Tianjin University (China)l Edinburgh Genome Foundry (UK); BioFAB University of Illinois (US); GeneMill, University of Liverpool; SYNBIOCHEM University of Manchester (UK)
Year(s) Of Engagement Activity 2018
URL http://www.synbicite.com/news-events/2018/jun/25/global-biofoundry-meeting-london-june-2018/
 
Description Royal Academy of Engineering/SynbiCITE visit 
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 Professional Practitioners
Results and Impact Visit of Chief Executive of The Royal Academy of Engineering and colleagues. The Chief Exec and 4 of her colleagues were given a tour and overview of SynbiCITE.....
Year(s) Of Engagement Activity 2017
 
Description Sky News at the SynbiCITE Foundry 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Sky News' report on the opening of the SynbiCITE Foundry for synthetic biology, 6th April 2016. Resulting in an increase in information requests.
Year(s) Of Engagement Activity 2016
URL http://www.synbicite.com/news-events/SynbiCITE-videos/sky-news-synbicite-foundry/
 
Description Synapse Connect Meeting 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Synapse is a student driven non-profit organisation in a the Copenhagen area that creates events, workshops and networking opportunities for students and young professionals with an interest in perusing careers in a life science environment. SynbiCITE, together with the Synthetic Biology Imperial College (SynBIC) organised talks with regard to synthetic biology in the UK. Professor Kitney spoke to the group and they were given a tour of the SynbiCITE labs. The Imperial College iGEM team gave a talk on their 2016 iGEM competition win.
Year(s) Of Engagement Activity 2017
 
Description UK BioFoundry meeting at iHub 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Attended by Earlham Biofoundry, Edinburgh Genome Foundry, Liverpool GeneMill, London SynbiCITE BioFoundry and Manchester SYNBIOCHEM Biofoundry. Discussion points included: Overview foundry team and close collaborators; Equipment and focus of expertise and activity; Approach to metrology; Training activities supported by the Biofoundry; Lessons learned from collaborations with academics and industry; Additional information & research examples.
Collaboration opportunities (protocols, method development, training); Business model - sustainability (funding sources, price structure benchmark); Advances in HT Synthetic Biology (automation and method development); Metrology and standards (protocols, phenotypes, references); Global Biofoundry Alliance - synergies and governance models; Trends in Synthetic Biology
Year(s) Of Engagement Activity 2019