An infrastructure for platform technology in synthetic biology

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

Abstract

Summary

The aim of the project is to develop integrated platform technology and an infrastructure for synthetic biology. Five British universities (Imperial College, Cambridge, Edinburgh, LSE/Kings and Newcastle), who are amongst the international leaders in synthetic biology, have formed a Consortium to address the issue. These universities already have very significant research programmes in synthetic biology (e.g. Imperial College has the EPSRC National Centre for Synthetic Biology and Innovation - CSynBI.)The consortium will provide the critical mass and synergy necessary to address a range of synthetic biology research and its translation to industry. Synthetic Biology can be defined as a field that "aims to design and engineer biologically based parts, novel devices and systems, as well as redesigning existing natural biological systems" (The Royal Academy of Engineering Synthetic Biology Inquiry Report. May 2009). It is a rapidly developing field which, it is now recognised, will have major relevance to enhancing the UK's industrial base. Britain, like much of the rest of Europe, has limited natural resources. The exception to this is high quality human resources - which have resulted in the UK being second only to the US in terms of our scientific research base. Synthetic biology is a field which naturally lends itself to the creation of new knowledge industries - and to enhancement of existing industries.

So why now? As with the original industrial revolution, it is not possible to single out a point in time from which everything flowed. However, a fiducial point was the invention of the steam engine by James Watt towards the end of the 18th century. Similarly, the publication of the structure of DNA by Watson and Crick in 1953 and the initial sequencing of the human genome in 2001 can be considered as fiducial points in the biological revolution which has spawned synthetic biology. Synthetic biology is the confluence of a number of fields, principally biology and engineering - but, also, mathematics, physics and chemistry. The ability to rapidly sequence and chemically synthesise DNA, coupled to information and communication technology (ICT), is the technological driver for Synthetic Biology. The scientific drivers are the accumulation of bio-knowledge over the last sixty years and the application of methods and concepts from engineering - for example, and importantly, modularisation, standardisation and characterisation.

Industrialisation is an important aim of synthetic biology. This will involve leveraging the UK's research base in synthetic biology to create new industries, to rejuvenate existing industries, to support SMEs, attract inward investment and create new jobs. To achieve this it will be necessary to create platform technology, comprising tools, processes etc, which can be applied across a range of fields. The platform technology will be used as part of a systematic design process involving the design cycle for synthetic biology (specifications, design, modelling, implementation, testing and validation) to produce biologically based parts, devices and systems - with a range of applications in different fields. An important aspect of the approach is the incorporation of ethical, societal and environmental considerations into the design process. A number of detailed exemplar applications projects will be carried out in close collaboration with industry to test the effectiveness of the infrastructure and platform technology as a vehicle for translating university-based research into industrial applications. The Consortium aims to provide knowledge hubs where firms in the field can share information and build strong networks and clusters. The objective is for the platform technology to be: (a) compatible with the work and aspirations of the international community and (b) readily accessible by a wide range of users (both academic and industrial).

Planned Impact

Synthetic Biology is an emerging field that is providing a conceptual framework for engineering biological parts, devices and systems based on the principles of standardisation, modularity and abstraction. Hence, the underlying concept is that standard biological devices can be built from standard parts and standard systems are built from standard devices. The key to this approach is data and information which can be analysed used and displayed. An important barrier to the commercial and practical exploitation of Synthetic Biology is the lack of effective tools (as discussed at a recent OECD meeting in Washington ). The work proposed in developing information tools for handling specifications, parts (BioParts) and standards will be a key step in enabling the industrial exploitation of synthetic biology - which is forecast to have a global market $2.4 billion in 2013, for a compound annual growth rate (CAGR) of 59.8%." (Bcc Research - Synthetic Biology: Emerging Global Markets - BIO066A - June 2009).

The project which we are proposing will make a real impact on the UK research community in Synthetic Biology. The involvement of 4 UK institutions will establish Synthetic Biology as a key priority for UK research, and will enable the field to make an impact on the UK research community in providing a source of information for the use of its standards, methods and parts. In addition the work of the project will help in setting international standards for Synthetic Biology, and contribute to the development of international, professional databases of BioParts though our collaboration with Stanford and Berkeley. There will be a significant impact on the international synthetic biology community though the publications and conference presentations from the 4 institutions involved, and will demonstrate the UK of at the forefront of this field

The work of the project will also benefit industry looking to adopt Synthetic Biology methods in its development of new products. The individual institutions already have collaborations with technology providers such as ATG:Biosynthetics, GeneArt and Febit, as well as product based companies in areas as diverse as pharmaceuticals, food technology, agroscience and biofuels and the establishment of this project will enable resources to be pooled to assist these industry sectors further. Edinburgh and Newcastle have good links with a number of SMEs throughout the UK; these companies will greatly benefit from the use of the synthetic biology tools which will be developed under the proposed project.

The web-based information infrastructure which will be developed will also have wider application in terms of training and teaching. Both Imperial College and Edinburgh have a strong educational programme comprising a final year undergraduate option in synthetic biology and an MRes/PhD Programme in Systems and Synthetic Biology. It is envisaged that the information infrastructure and the associated tools will significantly enhance the teaching of synthetic biology techniques at the four applicant institutions and in the wider academic and industrial community.

Publications

10 25 50
 
Description Flower Consortium Members: five British universities (Imperial College, Cambridge, Edinburgh, LSE/Kings and Newcastle).

The specific topics worked on in the project were: Information infrastructure, Standards and CAD, Data mining, Models and Modelling, Chassis characterisation, Parts and device characterisation, DNA Assembly, Applications, Innovation and impact.

The Flowers Project had several notable achievements:
•The community now has the ability to undertake multi-institutional research collaboration across the Flowers Consortium, enabling the cohesive development of platform technologies and the integration of tools and methodologies which will impact the ability to undertake systematic design.
•The definition and implementation of key emergent metrology concepts and standards (DICOM-SB and SBOL http://sbolstandard.org/ ) and their integration into an enabling IT infrastructure (SynBIS) - built to enable efficient information exchange and extraction. This facilitates knowledge aggregation and consolidation.
• The development of a modular model composition that supports model-based design (MBD) in synthetic biology - The Flowers Virtual Parts Repository 2.0 (VPR) (www.virtualparts.org). This repository supports MBD using modular models termed virtual parts for a number of popular modelling formalisms such as CellML, SBML and Kappa. The VPR supports and enhances the operation of CAD based tools for SynBio and has been used to design several 'real' synthetic biology systems that are being implemented and tested in the laboratory.
• The development of systems for characterising metabolic load in both Escherichia coli and Bacillus subtilis.
• Responsible Research and Innovation - Work package 5 members worked extensively to ensure social responsibility in research and innovation, proposing novel ways in which these RRI principles can be translated into practical procedures for the governance of synthetic biology.
Exploitation Route Synthetic Biology is an emerging field that is providing a conceptual framework for engineering biological parts, devices and systems based on the principles of standardisation, modularity and abstraction. The underlying concept is that standard biological devices can be built from standard parts, and standard systems are built from standard devices. The key to this approach is data and information that can be analysed used and displayed. An important barrier to the commercial and practical exploitation of Synthetic Biology has been the lack of effective tools. Hence a key aspect of the project comprised developing information tools for handling specifications, parts (BioParts) and standards. This is a key step in enabling the industrial exploitation of synthetic biology - which is now forecast to have a global market $56billion by 2025.

The tools and technical standards developed in the project (SBOL and DICOM-SB) are beginning to have a real impact on the UK and international research communities in Synthetic Biology. The involvement of four UK institutions through the Flowers Project, has helped to establish Synthetic Biology as a priority for UK and will enable the field to begin to make an impact on the UK Bioeconomy. This has been achieved through providing a source of information for the use of standards, methods (e.g. characterisation protocols) and parts. In addition, the work of the project has helped in setting international standards for Synthetic Biology - and to contribute to the development of international, professional databases of BioParts, through collaboration with NUS in Singapore, Berkeley and Stanford. There has also been significant impact on the international synthetic biology community though research publications and conference presentations from the four institutions involved in the Flowers Project.

The work of the project will also be benefited industry. Through the universities involved in SynbiCITE, the consortium has worked with well 20 start-ups and SMEs and given them support - in terms of their research and product development (e.g. CustoMem and LabGenius in the UK, and AdvanSyn in Singapore). These companies and others have benefitted from the use of the synthetic biology tools that have been developed in the Flowers Project.

A web-based integrated information infrastructure has been developed wide application for research, industrial translation, industrial development, as well as in education and training. The infrastructure comprises a full web-based information system for synthetic biology called SynBIS, a virtual parts registry and SynBioMine (a datamining software suite). These systems are all linked into the information infrastructure by software called POLEN. In the context of education and training, both Imperial College and Edinburgh have a strong educational programme comprising a final year undergraduate option in synthetic biology and an MRes/PhD Programme in Systems and Synthetic Biology. It is envisaged that the information infrastructure and the associated tools will significantly enhance the teaching of synthetic biology techniques at the four applicant institutions and in the wider academic and industrial community.
Sectors Agriculture, Food and Drink,Chemicals,Digital/Communication/Information Technologies (including Software),Education,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL http://synbis.bg.ic.ac.uk/synbis2/Welcome_Page.html
 
Description A Synthetic Biology Roadmap for the UK
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
Impact This report provides the vision and direction for supporting a world-leading synthetic biology community in the UK. Produced by an independent panel of experts for the government's Department for Business Innovation and Skills, it sets out a shared vision for realising the potential of synthetic biology in the UK. The roadmap aims to deliver a synthetic biology sector that is cutting edge; economically vibrant, diverse and sustainable; and of clear public benefit. Recommendations in the roadmap also provide a compass-bearing for the synthetic biology community, helping to align interests towards future growth opportunities, whilst identifying the resources and support needed to accelerate progress in the shorter term.
URL http://www.rcuk.ac.uk/publications/reports/syntheticbiologyroadmap/
 
Description PAS 246 - Use of standards for digital biological information in the design, construction and description of a synthetic biological system - Guide
Geographic Reach Europe 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact PAS 246 - Use of standards for digital biological information in the design, construction and description of a synthetic biological system. Is a standard and guide to the development and use of data pertinent to bio-manufacturing and biotechnology
URL http://shop.bsigroup.com/ProductDetail/?pid=000000000030303883
 
Description 7th International Workshop on Bio-Design Automation (IWBDA), University of Washington, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Flowers consortium members delivered presentations on Synthetic Biology Open Language SBOL and SynBad: an SVP design framework.
Year(s) Of Engagement Activity 2015
URL http://www.iwbdaconf.org/2015/program/IWBDA_2015_Proceedings.pdf
 
Description Imperial College Festival 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Public introduced to new emerging disruptive technology - Engineering Biology. Engineering of Biology to make really useful stuff. For example, seeing virtual reality labs and an introduction to new science that affects every day life. Including children's competitions, interactive technologies for all.
Year(s) Of Engagement Activity 2015,2016
URL http://www.imperial.ac.uk/festival/about/festival-2016/
 
Description Imperial College London IB and SB Technology Showcase 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The event showcased work going on at Imperial in the area of Engineering Biology. The event was hosted by the Synthetic Biology Hub and the Industrial Biotechnology Hub. Keynote talk on UK Government Strategy for Engineering Biology was Professor Janet Bainbridge OBE, and were further presentations from leaders in the field from industry and Imperial.
Year(s) Of Engagement Activity 2017
URL http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/eventssummary/event_9-5-2017-11-29-54
 
Description Imperial Insights Workshop: Synthetic Biology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Y10 Students inspired by synthetic biology and gained an insight into the research methods.

Students more likely to apply for science subjects
Year(s) Of Engagement Activity 2014
 
Description Leadership Excellence Accelerator Programme (LEAP) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Each year about twenty Fellows - emerging leaders working in diverse areas of biotechnology - are selected to participate.

LEAP envisions catalysing a next generation of leaders in synthetic biology by providing the environment to learn skills for engaging a broad range of stakeholders in the development of the field with a strong ethical foundation for the future.
LEAP does this by:
Investing in the individuals who will ultimately shape and govern this diverse, growing and globally distributed technology.
Providing them with new tools and networks essential to achieving their visions for promoting innovation responsibly in practice.
Acting as a sustaining nexus of resources and support as leaders assume their roles.
Year(s) Of Engagement Activity 2014,2015,2016,2017
URL http://www.synbicite.com/knowledge/leap/
 
Description iGEM competition and jamboree (UK & US) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact The iGEM Competition is the premiere student team competition in Synthetic Biology..

For over 10 years, iGEM has been encouraging students to work together to solve real-world challenges by building genetically engineered biological systems with standard, interchangeable parts. Student teams design, build and test their projects over the summer and gather to present their work and compete at the annual Jamboree.

Participation in the iGEM competition empowers teams to manage their own projects, advocate for their research and secure funding. Teams are also challenged to actively consider and address the safety, security and environmental implications of their work. The 2016 Imperial Team led by Dr Guy-Bart Stan and Dr Karen Polizzi, together with Profs Kitney and Freemont won the overall competition at the Jamboree, with their project which was entitled "Ecolibrium - developing a framework for engineering co-cultures". Profs Kitney and Freemont were judges at the 2017 Jamboree.
Year(s) Of Engagement Activity 2013,2014,2016
URL http://2016.igem.org/Main_Page