The CHELL : A Bottom-Up approach to in vitro and in silico Minimal Life-like Constructs
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Pharmacy
Abstract
This work is directed towards generating artificial objects that have properties mimicking those of biological cells. Specifically we set out to test if it is possible for an artificial cell to imitate a natural cell in terms of responding to biological signals. We do not aim to produce an artificial life-form but rather we seek to evaluate whether some processes (signals) that natural cells use can be imitated by the synthetic cells such that the natural cells are unable to tell the difference. The work will involve the modelling, design, preparation and evaluation of capsule-like structures using a combination of compuer science, chemistry, materials science, with a further focus on potential ethical and social aspects of artificial cellular systems. The cell-imitating capsules will contain chemistries we can use as models of signalling ands metabolism, and will be designed such that we can use the capsules and signals to/from them in 'conversations' and 'imitation games' with real cells.The work is intended as fundamental curiosity-driven investigation and addresses the scientific, societal and ethical aspects of minimal-life constructs, However, there are many potential spin-outs of this work if we show that it is indeed possible to 'talk' to natural cells via artificial capsules. Examples might include 'smart' antibiotics, drug carriers for locally-directed therapies and intelligent materials for tissue repair.
Publications
Alexander C
(2013)
Self-assembly of biopolymers - recent progress and future prospects
in Faraday Discussions
Alexander C
(2011)
Materials chemistry in the emerging field of synthetic biology
in Journal of Materials Chemistry
Bodo N
(2017)
Efficiency Evaluation of Fully Integrated On-Board EV Battery Chargers With Nine-Phase Machines
in IEEE Transactions on Energy Conversion
Leire E
(2016)
Dendrimer mediated clustering of bacteria: improved aggregation and evaluation of bacterial response and viability.
in Biomaterials science
Louzao I
(2015)
Cationic polymer mediated bacterial clustering: Cell-adhesive properties of homo- and copolymers
in European Journal of Pharmaceutics and Biopharmaceutics
Lui L
(2013)
Bacteria clustering by polymers induces the expression of quorum-sensing-controlled phenotypes
in Nature Chemistry
Lui LT
(2015)
Complexity measurement based on information theory and kolmogorov complexity.
in Artificial life
Magennis EP
(2014)
Bacteria-instructed synthesis of polymers for self-selective microbial binding and labelling.
in Nature materials
Magennis EP
(2017)
Polymers for binding of the gram-positive oral pathogen Streptococcus mutans.
in PloS one
Magnusson J
(2011)
Synthetic polymers for biopharmaceutical delivery
in Polym. Chem.
| Title | Online video and artwork |
| Description | Video and artwork produced in collaboration with designer James King http://seedmagazine.com/content/article/slippery_cellularities/ |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2011 |
| Impact | IMPACT Exhibition with EPSRC Cheltenham Science Festival New approaches to work with designers from the Royal College of Art - ongoing |
| URL | https://vimeo.com/10274649 |
| Description | The project aimed at producing artificial Chemical Cells (or CHELLs) using synthetic polymers to contain emergent chemical reactions which in turn could act as signals to bacteria. The experimental work was designed as a first test of a 'Synthetic Biology Imitation Game' or 'Turing Test'of artificial intellligence as first set out in Cronin L et al, Nature Biotechnology 2006. We intended at the start of the project to use new chemistries and computation to evaluate whether the chemical cells could cross-talk with bacterial populations, thus imitating the behaviour of real biological cells, albeit in a simplified sense. The ability of the synthetic cells to intervene in natural signalling processes might enable not only control of unwanted bacterial behaviour such as infection, but also might eventually be able also to guide design of truly 'smart' therapeutic capsules, which administer therapy in response to changes in the body. While we remain a long way from the latter goal, the data generated has given some intriguing insights into how synthetic materials interact with bacterial populations, and we were able to show, and more recently provide a mechanism for, how feedback occurs between synthetic materials and several bacterial types.We now have some design rules which should facilitate the preparation of new anti-infective materials and also containers for 'cell factories' in which potentially valuable secondary metabolites can be produced |
| Exploitation Route | In addition to possible commercial exploitation of the materials, we have used the project to foster public dialogie on Synthetic Biology. Working with the designer James King, who developed an exhibit and a film on the project for the EPSRC IMPACT exhibition and the Cheltenham Science Festival, we have explored how a synthetic biology 'product' might look and how it might be used. We have carried out further public dialogue via the SynBioNT EPSRC/BBSRC Network, and promoted debate on synthetic biology via YouTube webcasts. A further impact of the project has been the adoption of the term 'Chell' for Chemical Cell in a number of publications written by commentators and social scientists with no connection to this grant - thus the word has acquired a meaning beyond the project itself. We have been in discussion with a number of industrial companies regarding new anti-infective polymers based on the results of this work. The fundamental science underlying the work has been published in leading academic journals and several more papers are in press or in final draft stage. Ideas set out in our original grant have been taken up by others, and a recent high profile paper "Two-Way Chemical Communication between Artificial and Natural Cells" by Lentini R, et al. ACS Cent Sci 3, 117-123, 2017. DOI: 10.1021/acscentsci.6b00330 has been published which validates our principal concept. Two PhD students associated with the project have been appointed to a full UK lectureship and a post-doctoral research fellowship at a world-leading polymer synthesis lab. The principal post-doctoral researcher (Dr Francisco Fernandez-Trillo) employed on the project was awarded a prestigious Birmingham Research Fellowship and so is now pursuing a fully independent academic career in the UK. The second PDRA, Dr Iria Louzao, moved to a post with the EPSRC Centre for Innovative manufacture in Additive manufacturing, thus transferring chemistry skills to pharmacy and engineering, and is now back in Spain as a tenure-track researcher. There has been a recent surge of work in cell-mediated chemistry, with papers from the Joshi group in the US in PNAS, and Guoping Chen's group in China citing this research. Chen et al published in Chemical Science and we published a cell-mediated polymerisation in Jan 2020 in Angewandte Chemie, the leading general chemistry journal. |
| Sectors | Chemicals Digital/Communication/Information Technologies (including Software) Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
| URL | http://www.test-tube.org.uk/videos/pages_meet_cameron_alexander.htm |
| Description | Outputs currently academic: award of 2 CASE grants, training of 2 PhD students, and contributed to 2 Nature family papers. BBSRC Industrial CASE with GSK Consumer Healthcare. BB/H53052X/1 "Bacterial Autonemesis" 2009-2013. Total value ~ £ 73,110 EPSRC DTG CASE ""Development of polymeric coatings for the systemic delivery of Adenovirus" - with PsiOxus Therapeutics £23,041 industry contribution |
| First Year Of Impact | 2009 |
| Sector | Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Cultural Economic |
| Description | 'The 'Chell' inspired 'Turing Test' for artificial life cited in Synthetic Biology Research Centre bids |
| Geographic Reach | National |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Description | Appointment to EPSRC Big Ideas Advisory Group |
| Geographic Reach | National |
| Policy Influence Type | Membership of a guideline committee |
| URL | https://epsrc.ukri.org/newsevents/news/theworldneedsbigideas/ |
| Description | Programme Grant |
| Amount | £5,365,958 (GBP) |
| Funding ID | EP/N006615/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2015 |
| End | 11/2020 |
| Description | University of Glasgow |
| Organisation | University of Glasgow |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Co-hosting of researchers in Chell collaboration |
| Collaborator Contribution | Co-hosting of researchers in Chell collaboration |
| Impact | Papers in leading journals Multidisciplinary collaboration linking chemistry, pharmacy and physics |
| Start Year | 2006 |
| Description | University of Oxford |
| Organisation | University of Oxford |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Hosting of researchers from Oxford. Knowledge transfer |
| Collaborator Contribution | Hosting of Nottingham PDRAs and PhDs. |
| Impact | Papers (see outputs) Collaboration involved chemistry, pharmacy and microbiology |
| Start Year | 2006 |
| Description | EPSRC IMPACT! Exhibition |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Exhibition or artwork designed by James King based on projects in the "Chell" project and my Leadership Fellowship grant. Artwork and film to explore concepts in what products from synthetic biology might look like Requests for articles and participation in further Synthetic Biology dialogues |
| Year(s) Of Engagement Activity | 2010 |
| Description | Publication and feature in EPSRC Pioneer Magazine |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Feature article in Pioneer 9 regarding Leadership Fellowship and also leading the EPSRC/AstraZeneca/Nottingham Centre for Doctoral Training in Targeted Therapeutics. http://www.epsrc.ac.uk/newsevents/pubs/mags/pioneer/Pages/pioneerdownloads.aspx . Queries from journalists and subsequent press releases |
| Year(s) Of Engagement Activity | 2013 |
| URL | http://www.epsrc.ac.uk/newsevents/pubs/mags/pioneer/Pages/pioneerdownloads.aspx |
| Description | Web videos |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Web-based videos produced and devised by journalist Brady Haran featuring science at Nottingham. Series of videos describing science and scientists at Nottingham Journalists asked for interviews |
| Year(s) Of Engagement Activity | 2009 |
| URL | http://www.youtube.com/watch?v=ThgJHeDKsxA |
| Description | YouTube videos |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Podcast developed by journalist Brady Haran to disseminate information regarding science at Nottingham. Ongoing videos as part of Brady Haran's 'Test-Tube' science video series I received numerous requests to participate in new research programs, and enquiries from potential PhD students. |
| Year(s) Of Engagement Activity | 2008,2010,2012 |
| URL | http://www.tes.co.uk/teaching-resource/Cameron-Alexander-Interview-6394346 |