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
Pasparakis G
(2009)
Diol-boronic acid complexes integrated by responsive polymers-a route to chemical sensing and logic operations
in Soft Matter
Smaldon J
(2010)
A computational study of liposome logic: towards cellular computing from the bottom up.
in Systems and synthetic biology
Pasparakis G
(2010)
Controlled polymer synthesis--from biomimicry towards synthetic biology.
in Chemical Society reviews
Magnusson J
(2011)
Synthetic polymers for biopharmaceutical delivery
in Polym. Chem.
Yasayan G
(2011)
Responsive hybrid block co-polymer conjugates of proteins-controlled architecture to modulate substrate specificity and solution behaviour
in Polymer Chemistry
Alexander C
(2011)
Materials chemistry in the emerging field of synthetic biology
in Journal of Materials Chemistry
Xue X
(2011)
Synthetic polymers for simultaneous bacterial sequestration and quorum sense interference.
in Angewandte Chemie (International ed. in English)
Yasayan G
(2012)
Well-defined polymeric vesicles with high stability and modulation of cell uptake by a simple coating protocol
in Polymer Chemistry
Alexander C
(2013)
Self-assembly of biopolymers - recent progress and future prospects.
in Faraday discussions
Lui LT
(2013)
Bacteria clustering by polymers induces the expression of quorum-sensing-controlled phenotypes.
in Nature chemistry
Magnusson JP
(2014)
Programmed assembly of polymer-DNA conjugate nanoparticles with optical readout and sequence-specific activation of biorecognition.
in Nanoscale
Sicilia G
(2014)
Programmable polymer-DNA hydrogels with dual input and multiscale responses.
in Biomaterials science
Magennis EP
(2014)
Bacteria-instructed synthesis of polymers for self-selective microbial binding and labelling.
in Nature materials
Lui LT
(2015)
Complexity measurement based on information theory and kolmogorov complexity.
in Artificial life
Louzao I
(2015)
Cationic polymer mediated bacterial clustering: Cell-adhesive properties of homo- and copolymers.
in European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
Leire E
(2016)
Dendrimer mediated clustering of bacteria: improved aggregation and evaluation of bacterial response and viability.
in Biomaterials science
Purdie L
(2016)
Influence of Polymer Size on Uptake and Cytotoxicity of Doxorubicin-Loaded DNA-PEG Conjugates.
in Bioconjugate chemistry
Marques L
(2016)
Highly sensitive optical fibre long period grating biosensor anchored with silica core gold shell nanoparticles.
in Biosensors & bioelectronics
Magennis EP
(2017)
Polymers for binding of the gram-positive oral pathogen Streptococcus mutans.
in PloS one
Bodo N
(2017)
Efficiency Evaluation of Fully Integrated On-Board EV Battery Chargers With Nine-Phase Machines
in IEEE Transactions on Energy Conversion
| 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 | 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 |