Engineering Fellowships for Growth: Development of SimCells as building blocks for synthetic biology

Lead Research Organisation: University of Oxford
Department Name: Engineering Science

Abstract

The vision of this Fellowship is to establish an unprecedented new bioengineering platform for synthetic biology - the SimCell (Simple and Simulated Cell) that performs advanced bioengineering functions in an easy-to-use, safe-to-handle, and reliable-to-build manner. The aim of this fellowship is to develop SimCells as programmable 'bio-robots' and establish the foundation for standardised engineering applications of SimCells. SimCells have the potential to open up a new frontier, enabling the development of new and smart materials for bioprocessing and manufacturing, bioenergy, healthcare, agriculture and environmental monitoring and protection. Unlike a living cell, a SimCell is a chromosome-free and simplified cellular bio-robot; its 'hardware' is the optimised 'shell' of a cell which enables specific cellular properties; and its 'software' is a piece of DNA which delivers the defined functions. The optimised shell and simple DNA in SimCells enables them faithfully delivering most of their energy and resources to a specific function without interference of unwanted pathways and networks in a natural cell. A SimCell is a non-dividing, biochemically active, designable and simplified agent, which can be continuously produced by engineered parent cells, but which cannot reproduce itself, making it more acceptable to public opinion than living genetically modified organisms (GMOs).
The Fellowship is truly revolutionary, transforming current synthetic biology based on living cells or cell-free system by providing an intermediate building block between them and taking advantages of both. It directly addresses three of five great challenges of synthetic biology by establishing novel SimCells as predictable, simple, safe and programmable bio-robots. The application of SimCells would lead to address one of challenges in 'the third industrial revolution' - bioenergy.
To demonstrate SimCells as miniature factories with high energy transfer efficiency, a bio-transformation system will be designed to produce biofuels (such as ethanol and alkanes) from H2O and CO2, mediated by SimCells and powered by electrons and sunlight. This will be built on the established synthetic pathways developed by WH's previous research and patents. The outcomes of this Fellowship will set a bioenergy benchmark to which other long-term projects will aspire, and will also create the infrastructure for a wide range of applications.

Planned Impact

The beneficiaries of SimCells research are wide ranging and there are a variety of routes in which to impact on the bioeconomy. SimCells will be developed as user-oriented 'bio-robots' with novel and controllable functions. Since they are non-living organisms, SimCells are a safe and robust enzyme system, which potentially can be purchased by end-users and used as building blocks by 3-D printers to build novel devices.
The strategic route to implement the impact is to establish a UK academic-Industry SimCell research club to rapidly disseminate the technology to the relevant companies in the UK, and expand the impact of the project to overseas market. The objectives of this SimCell club are:
1) To identify key area of SimCell applications;
2) To establish a pathway to commercialisation;
3) To promote making prototype products;
4) To explore opportunity of Intellectual Property (IP) issues;
5) To spin out a company by working with Sheffield Research and Innovation Services
The primary route for dissemination and acceleration of impact will be via the SimCell club, open source platforms in order to extend the reach and accessibility of research. This fellowship will enable the establishment of a SimCell bank, which allows users to submit and share data on the performance and characterisation of SimCells. Beneficiaries will be able to utilise the SimCells building blocks in developing bespoke solutions to engineering challenges. Usage of the research outputs will be encouraged via presentations, seminars and lectures at other institutes and related conferences. Exploitation of SimCells in conjunction with industrial partners and sponsors, will begin with applications in specific engineering challenges to ensure the high-value uptake of the SimCells platform.

Publications

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Berry D (2015) Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells. in Proceedings of the National Academy of Sciences of the United States of America

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Chen J (2019) Development of Aspirin-Inducible Biosensors in Escherichia coli and SimCells in Applied and Environmental Microbiology

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Fan C (2019) Defensive Function of Transposable Elements in Bacteria. in ACS synthetic biology

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Fan C (2020) Chromosome-free bacterial cells are safe and programmable platforms for synthetic biology. in Proceedings of the National Academy of Sciences of the United States of America

 
Description A SimCell is a simple and simulated cell whose chromosome has been removed and replaced with designed DNA. SimCells are continuously produced by designed parent cells, and its 'hardware' is the optimised 'shell' of a cell, which enables specific cellular properties; its 'software' is a piece of designed DNA which delivers defined functions.
A SimCell is non-dividing, biochemically active, designable platform for synthetic biology. It is a new type of cell system falling between a living cell and a cell-free system, taking advantage of the machinery of living cells on the one hand, and of the safe, controllable and predictable performance of cell-free in-vitro gene expression systems on the other.
SimCells can be regarded as smart bioparticles, which have a broad application to medicine diagnosis and treatment, biofuel production, biosensing for environmental pollutions, and bio-inks for 3D cell printing.
Exploitation Route Five ways to disseminate the findings:
1. Seminar and conference talks. For example, I will give a talk on a Gordon Conference: Renewable Energy: Solar Fuels to demonstrate that how to apply SimCells for biofuel production.
2. Journal paper publications. Two papers are in preparation to report the findings.
3. Workshops. Oxford will organise a few workshop to discuss industry collaboration focusing on SimCell application.
4. Industry application. We are in the process of application of Simcells for controlling stem cell differentiation by collaborating with regenerative medicine centre in Oxford.
5. Working with public media. We will meet public media such as New Scientist to report our findings.
Sectors Agriculture, Food and Drink,Chemicals,Energy,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description 1. Two biosensor strains have been adopted as national standards for toxicity detection in contaminated water including fresh water and seawater. The standardisation is at the stage of waiting for final approval. 2. Oxford University and investors have set up a biosensor spin-off company: Oxford Molecular Biosensors (www.omb.co.uk). 3. A patent about SimCells (simple and simulated cells) technology has been filed on 25th Oct 2019. A US company Flagship Pioneering Ltd is under discussion with Oxford University about the licensing. 4. A spin-off company - Oxford SimCell Ltd has been set up in Feb 2020. The new company will use SimCell technology for medical and environmental applications. 5. SimCell technology will be used to as a novel system for drug delivery, working with Novo Nordisk and other international companies.
First Year Of Impact 2016
Sector Creative Economy,Environment,Government, Democracy and Justice,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic,Policy & public services

 
Description Associate Editor of Synthetic biology for Microbial Biotechnology Journal
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact I served as an associate editor of Microbial Biotechnology from 2019. I am responsible for synthetic biology section. Typical contributions consist of short pieces (1000-1500 words, at most one display item) reporting new concepts, raising questions (including those challenging conventional wisdom or established tenets) and outlines for new applied and basic endeavours. It influences the policy makers, provides education to the public and stimulates the discussion in academia.
URL https://onlinelibrary.wiley.com/doi/full/10.1111/1751-7915.13337
 
Description Biosensors were applied to water quality modelling and management
Geographic Reach Africa 
Policy Influence Type Influenced training of practitioners or researchers
Impact Over 2 days (Feb 4-5th 2020) Prof Paul Whitehead gave a training course on Water Quality Modelling at the Water and Land Resource Centre at Addis Ababa University. 13 people attended from a range of catchment authorities in Ethiopia representing the Awash River, the Blue Nile and the Rift Valley River systems. In addition, stakeholders from the Federal EPA for Ethiopia attended. Following introductory lectures on water quality modelling, Paul distributed copies of the INCA training model for flow, nitrate and ammonia and extensive training/practical sessions were undertaken. The new versions of INCA set up for the Awash River system were provided and a set of scenarios for point source and agricultural runoff were evaluated. In addition, new model setups for the INCA Metals model version were established to model metals in the Awash, Akiki and Rift Valley catchments. Sets of scenarios were evaluated to evaluate potential clean up scenarios with most concern over the highly toxic Chromium, lead, zinc and cadmium coming from Tannery effluents. Paul also gave a presentation on Biosensors for cell and genetic toxicity in contaminated rivers, lakes and soils. This was also of interest to Ethiopian colleagues because of the need to rapidly determine water toxicity in a rural environment. The Biosensors provide this possibility-see recently published paper below. This training workshop was funded by the DFID REACH programme as part of the Oxford Reach Programme -- see www.reachwater.org.uk
 
Description National standard for toxicity detection in contaminated water
Geographic Reach Asia 
Policy Influence Type Citation in other policy documents
Impact Chinese government has adopted two biosensors as national standards for ocean contamination monitoring.
 
Description Training Oxford Synbio DTC students
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Engineering new capacities for solar energy utilisation in bacteria
Amount £4,248,968 (GBP)
Funding ID BB/M000265/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 02/2015 
End 01/2020
 
Description Liquid Fuel and bioEnergy Supply from CO2 Reduction
Amount £1,924,296 (GBP)
Funding ID EP/N009746/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2016 
End 12/2020
 
Title Novel technology to generate SimCells 
Description We developed a novel method to generate chromosome-free SimCells. Flagship Pioneering Ltd in the US is under discussion with Oxford University about the licensing. 
Type Of Material Biological samples 
Year Produced 2020 
Provided To Others? Yes  
Impact A patent has been filed on 25th Oct 2019, GB201711660D0. The patent has attracted the attention from Flagship Pioneering Ltd. The paper has been published at a prestigious journal: Proceedings of the National Academy of Sciences of the United States of America (PNAS). 
URL https://www.pnas.org/content/early/2020/03/02/1918859117.long
 
Description CAS Bioenergy collaboration 
Organisation Chinese Academy of Sciences
Country China 
Sector Public 
PI Contribution Prof Jian Xu is Director of BioEnergy Directorate, Qingdao Institute of BioEnergy and Bioprocess Technology (QIBEBT), Chinese Academy of Sciences, has established a formal collaboration with me on bioenergy research. They will characterise novel gene from algae, which will be introduced into our SimCells to biofuel production.
Collaborator Contribution He has visited Oxford in Dec 2015. He has paid my travelling, accommodation cost (about CYN20K) to visit China and give a talk in his institute. He would like to pay and get a licence for this technology.
Impact We are in the process of commercialization collaboration.
Start Year 2007
 
Description Collaboration with Baojun Wang on SimCell biosesors 
Organisation University of Edinburgh
Department School of Biological Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Our SimCell biosensor can be applied to contaminant detection without issue of genetically modified organisms (GMO). SimCells can be used as novel and safe chassis for gene circuit for chemical sensing systems and applied to the problems of the real world.
Collaborator Contribution Dr Baojun Wang is a research fellow at Edinburgh University, who is developing gene amplifier to enhance biosensor sensitivity. We collaborate to apply the gene amplifier to SimCells which can be further developed as biosensor for the detection of drinking water contamination.
Impact We are in the process of paper preparation.
Start Year 2016
 
Description Collaboration with Prof Neil Hunter 
Organisation University of Sheffield
Department Department of Music
Country United Kingdom 
Sector Academic/University 
PI Contribution This research is also involved in BBSRC funded sLoLa project: Engineering new capacities for solar energy utilisation in bacteria (BB/M000265/1). Prof Neil Hunter, FRS is a PI of this project. We plan to use SimCells as novel catalysts for light energy harvesting and make products.
Collaborator Contribution I am a Co-I of this BBSRC sLoLa project (BB/M000265/1) which offers a postdoc researcher (jointly with Prof Neil Hunter at Sheffield University) and cover some of my time.
Impact We are currently prepare three research papers.
Start Year 2010
 
Description Collaboration with Prof Petra Oyston in DSTL 
Organisation Defence Science & Technology Laboratory (DSTL)
Country United Kingdom 
Sector Public 
PI Contribution Confidential
Collaborator Contribution Confidential
Impact Confidential
Start Year 2017
 
Description Partnership with Jiangsu Industrial Technology Research Institute China 
Organisation Jiangsu Industrial Technology Research Institute
Country China 
Sector Charity/Non Profit 
PI Contribution Jiangsu Industrial Technology Research Institute (JITRI) has funded a collaboration via Oxford Suzhou Centre for Advanced Research (OSCAR). We constructed a series of biosensor in Oxford, which are potentially useful to real world problems.
Collaborator Contribution In July-October 2018, JITRI funded 300k RMB to understand the biosensor technology and investigate the market. A further investment via OSCAR is still on going.
Impact JITRI has agreed that biosensors we developed are very useful to monitor environmental pollution in China. JITRI is planning to invest further in OSCAR on biosensors.
Start Year 2018
 
Description Partnership with National Institute for Laboratory and Inspection Body China 
Organisation Beijing National Institute for Laboratory and Inspection Body
Country China 
Sector Charity/Non Profit 
PI Contribution We developed a series of biosensors which can be applied to environmental pollution monitoring, medical diagnosis and biomanufacturing.
Collaborator Contribution National Institute for Laboratory and Inspection Body (hereinafter referred to as "CNLAB") is a comprehensive service research institute which undertakes mandatory approval and accreditation, standard revision and establishment, technical training, technical consulting, international communication and marketing for inspection bodies and laboratories in China. The institute has professional research team, marvellous technical ability, top expert team, completed curriculum design, rich training experience and smooth information resources. It is the technical support institute for the national mandatory approval management department, national accreditation organisation and inspection body and laboratory. CNLAB will provide free consultancy for standardisation of biosensors and provide government advise about use of biosensors to diagnosis, environmental pollution monitoring and manufacturing.
Impact A MOU has been signed between Oxford Suzhou Centre for Advanced Research (OSCAR) and CNLAB. CNLAB will organise a workshop to market biosensor technology that developed in Oxford.
Start Year 2018
 
Description Partnership with Suzhou Industry Park 
Organisation Suzhou Industry Park
Country China 
Sector Public 
PI Contribution We develop technologies for preventing pollution, stimulating microbial clean-up of waste waters, and their biotransformation to high value chemicals.
Collaborator Contribution Oxford Suzhou Centre for Advanced Research (OSCAR) is wholly governed by Oxford University. Located in China, and more specifically Suzhou Industry Park (SIP), OSCAR offers many strategic benefits to Oxford's research mission through access to state-of-the-art facilities, a research environment enriched by numerous universities and Chinese Academy Institutes, and a substantial company base including more than 90 Fortune 500 companies as well as many hundreds of SMEs. OSCAR will benefit Oxford via: 1. Proximity to industry and Chinese science and technology institutes. 2. OSCAR offers an opportunity to pursue research in a setting where scientific possibilities or potential routes to application are not available in the UK. For example, work on plastic electronics will benefit from proximity to major display screen manufacturers in the Far East (a sector with only one UK company); 3. Closer working with industry will lead to faster adaption of new research into commercially available technologies, accelerating the impact of our research; Researchers will be in a position to collaborate more closely with their Chinese partners, growing Oxford's relationship with universities, research institutes and high-tech enterprises in China. 4. SIP also offers access to state-of-the-art facilities (e.g. in the adjacent Chinese Academy of Sciences Institute of Nano-Tech and Nano-Bionics) Access to talented researchers OSCAR provides a vehicle for talented state-funded Chinese national postgraduate research students to return to China whilst continuing their research in collaboration with Oxford-based labs, retaining the skills they developed during their doctoral study; A well-resourced Centre in China will strengthen our position to attract the top-quality students and postdoctoral researchers to work on Oxford-led research projects. OSCAR also offers a window in South East Asia through which Oxford can better showcase its true nature, addressing the perception that many have of Oxford producing politicians and not scientists - OSCAR will demonstrate Oxford's world-leading position in scientific research and innovation. In the longer term, OSCAR will seek to support academics in medical sciences, the humanities, and social sciences in advancing research programmes in China.
Impact A high quality research lab has been established in OSCAR. Collaborations with local industry are on going.
Start Year 2018
 
Description Partnership with Tsinghua University 
Organisation Tsinghua University China
Department School of Enviroment
Country China 
Sector Academic/University 
PI Contribution Oxford Suzhou Centre for Advanced Research (OSCR) and Research Institute for Environmental Innovation (Suzhou), Tsinghua University (RIET) have formally signed a MOU. OSCAR is the first oversea institute of Oxford University and I am involved in OSCAR as a PI, working on synthetic biology application to environment biotechnology.
Collaborator Contribution RIET is a secondary institute affiliated to Tsinghua University. It is mainly engaged in environmental science and innovation activities, with its overall objective to build a comprehensive research & development and science & technology service institute with international influences, which is to help Tsinghua University's development strategy of "building a world-class discipline of environment", driven by the institutional innovation, based on the major scientific and technological research and development, and oriented with the grounding of industrialisation of research results. My team in OSCAR developed a series of biosensors. RIET provides research facility, scientists and industrial partners working on biosensor application to environment. RIET is also working with OSCAR for joint project, exploiting research funding in China.
Impact We have jointly standardalised two biosensors for toxicity detection as Ocean standards in China.
Start Year 2018
 
Description  
IP Reference  
Protection Trade Mark
Year Protection Granted
Licensed No
Impact I and Prof Ian Thompson have founded an Oxford spin-off company- Oxford Molecular Biosensors (https://www.omb.co.uk/) (OMB). Recently OMB has received the funds from an international company - Sembcorp and Innovate UK to develop COD biosensors. The core technology of OMB is based on the technology developed in this grand funded research.
 
Description  
IP Reference  
Protection Trade Mark
Year Protection Granted
Licensed Yes
Impact This is the first report to develop SimCells (simple cells) as novel chasses for synthetic biology. SimCells were developed in this work which inherited machinery from living cells and contained designed gene circuit for biosensing function. It demonstrated that SimCells can be potentially regarded as 'artificial cellular machine' with various functions. SimCells as programmable chasses open a new frontier for synthetic biology and its broad application without GMO (genetically modified origanisms) issues. It inspired a few companies around world including China, US and Switzerland. For example, after reading this paper, Flagship Pioneering (FP) Ltd in the US has contacted. Associate Director of FP Dr Hok Hei Tam and his colleague have visited me and Oxford University Innovation (OUI). A consultancy agreement and know-how transfer has been signed by OUI. FP has set up a company- FL62, and invested (>$1M) a project based on this SimCell technology.
 
Company Name Oxford Molecular Biosensors 
Description OMB is offering a range of products and services, including several biosensors with differing functionalities, greater robustness and sensitivities than those currently on market. The company has also developed a platform technology which enables rapid design and construction of bespoke biosensors tailored to the specific needs of the customer. A further development is a portable device which will enable biosensor assessment to be made on site and in remote locations. License agreements to employ our biosensors, training courses for their application and data analysis as well as consultation on best measures for remediation of contamination are also available. 
Year Established 2017 
Impact Provide service to Primark, Bangladesh government water project.
Website https://www.omb.co.uk/
 
Description Research Expo St Edmund Hall 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The second St Edmund Hall Research Expo will take place on Saturday 25 February 2017 (6th Week), 12:30-5:00pm. Once again, the College will showcase the wide diversity of research being undertaken by its students and academics - from undergraduates to Fellows - via sessions of short 'Teddy Talks' (all aimed at a non-specialist audience) and three rooms of interactive displays and exhibits.
Year(s) Of Engagement Activity 2017
URL https://www.seh.ox.ac.uk/expo
 
Description Talk at Gordon Conference (GRC): Renewable Energy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited to give a presentation about SimCells developed in Oxford, funded by this EPSRC grant.
Year(s) Of Engagement Activity 2016
URL https://www.grc.org/programs.aspx?id=13576