Sandpit: The Programmable Rhizosphere
Lead Research Organisation:
University of Cambridge
Department Name: Plant Sciences
Abstract
Humans have striven for centuries to control and exploit living organisms for their own purposes. Agricultural practices have been developed to maximise the yield of plants and animals. More recently, microbial systems have been manipulated to increase their utility in the food, biotech and brewing industries. Many of these changes have been achieved through breeding and chance selection for improved agronomic characters. Recent developments in genetic engineering have allowed scientists to apply precise perturbations that lead to beneficial changes in an organism. However, the complexity of biological systems makes it difficult to manually design and implement large changes that predictably produce an intended phenotype using conventional genetic engineering techniques. Our ability to synthesise DNA far outstrips our ability to design new genetic systems. Synthetic Biology holds the promise of rational design and reproducible fabrication of biological circuits that can be used to introduce a desired function in an organism. One of the main premises of this approach is that engineering principles should be applied to the design of modular circuits from well-characterized parts and components, using defined composition rules. A framework that enables this approach to the engineering of biology has, to date, been lacking. In this project, we propose to develop such a framework, and a unique library of new DNA parts. Specifically, we propose to tackle the problem of how cellular circuits in organisms (such as microbes and plants) can be designed in to self-organise and interact with other organisms in a predictable and robust fashion. To this end we will develop novel mathematical and computational approaches that automatically transform a quantitative description of a desired function into a circuit design that implements this function in bacteria. In addition we will generate a collection of DNA parts that will allow the construction of new channels of communication between different cell populations or organisms, and the pathways for symbiotic exchange of nutrients. There are many situations where improvements in the ability to regulate cells, and to form stable new ecologies, would be of benefit to humans. These range from applications in tissue engineering through to bioremediation, biotechnology and bioenergy. In this project we have chosen to focus on the relationship between plants and soil bacteria that normally live alongside the root system. We wish to engineer communication between a model bacterium and model plant, to allow negotiation and establishment of a new symbiotic relationship. The system would have many applications for improvements in sustainable agriculture, bioproduction and food security, such as improvements in soil use, pest resistance, weed suppression and creation of new crop plants capable of nitrogen fixation.
Planned Impact
Beneficiaries of the research:This is an ambitious project which, if successful, has the potential to impact on many areas of society, including the larger life science and biotechnology community, government and regulatory agencies, and even the agricultural industry. The larger biotechnology community - tools and methodologies: The ability to engineer cellular function in time and space is a critical underlying capability for many applications in biological engineering. Therefore, the successful execution of this research project will provide the foundations for broader efforts in engineering complex biological systems. The experimental and model-based toolchain will be developed as a technology platform, making it universally applicable in bio-based technologies at large, including synthetic biology, systems biology and metabolic engineering. Government / regulatory agencies: All investigators on this project have actively engaged with government and regulatory bodies in the past, including describing the potential impact their research can have towards the economic development of the nation, serving as reviewers on other projects, and as sources of information on issues related to synthetic biology. The results that arise from this project will be an important consideration in the formulation of policies related to synthetic biology applied to agricultural research. Society - awareness, engagement through extension services, and ethical considerations: Over the term of this project, we will direct effort to communicating and sharing our research efforts, goals, and implications to the agricultural stakeholder community, through presentations, informational literature and relevant newsletter articles in conjunction with outreach, education and public engagement exercises. In addition, we are promoting the development and adoption of standards within the biology community. This includes the generation of standardised educational materials for Synthetic Biology and promoting the distribution of strains and protocols for practical teaching. This research will connect to the Edinburgh-Stanford research project on Synthetic Aesthetics, which aims to integrate aesthetic concerns into synthetic biology projects and products, enabling inclusive and responsive technology development. Impact on teaching in the classroom: All investigators teach graduate and undergraduate courses which incorporate elements relevant to their respective research contributions in this project. Outcomes of this research, including tutorials on mathematical modeling of biological systems and design criteria for regulatory systems and communication modules will be incorporated into the courses currently taught by the investigators. Mentoring undergraduates for iGEM: Each investigator actively participates as an adviser in the annual iGEM contest. The project will contribute to the promotion of interdisciplinary educational challenges in Synthetic Biology. Dissemination and exploitation of research results: The following routes will be utilized for the broadest possible dissemination of research results: 1) Publication through scientific journals of the highest quality. 2) Publication through posters, presentations and papers at technical conferences and annual meetings of professional societies such as American Chemical Society and Institute of Biological Engineering. 3) web-based distribution of software and data, 4) Publication of research protocols via OpenWetWare, a Wiki-based system for the sharing of information related to synthetic biology. 5) Servicing requests for genetic materials as per institutional guidelines.
People |
ORCID iD |
James Haseloff (Principal Investigator) | |
Anil Wipat (Co-Investigator) |
Publications
Rudge TJ
(2013)
Cell polarity-driven instability generates self-organized, fractal patterning of cell layers.
in ACS synthetic biology
Rudge TJ
(2016)
Characterization of Intrinsic Properties of Promoters.
in ACS synthetic biology
Rudge T.J.
(2012)
Computational modeling of synthetic microbial biofilms
in ACS Synthetic Biology
Misirli G
(2013)
BacillOndex: an integrated data resource for systems and synthetic biology.
in Journal of integrative bioinformatics
Misirli G
(2011)
Model annotation for synthetic biology: automating model to nucleotide sequence conversion
in Bioinformatics
Misirli G
(2016)
Annotation of rule-based models with formal semantics to enable creation, analysis, reuse and visualization.
in Bioinformatics (Oxford, England)
Misirli G
(2014)
BacillusRegNet: a transcriptional regulation database and analysis platform for Bacillus species.
in Journal of integrative bioinformatics
Grant PK
(2016)
Orthogonal intercellular signaling for programmed spatial behavior.
in Molecular systems biology
Federici F
(2013)
Synthetic Biology: opportunities for Chilean bioindustry and education.
in Biological research
Aquea F
(2012)
A molecular framework for the inhibition of Arabidopsis root growth in response to boron toxicity.
in Plant, cell & environment
Description | The research was part of a US-UK effort to establish synthetic mechanisms for engineering plant-microbe associations. This involved to use of a model plant system, Arabidopsis, and a strain of a common soil bacterium. The UK-based work was split between the University of Cambridge and the University of Newcastle. The Cambridge work aimed to construct artificial systems for cell-cell signalling and cross-feeding. A peptide-based signalling system was established in Bacillus subtilis, along with work in Newcastle to determine the complete genome sequence of the Marburg strain of the bacterium, which has phytoprotective properties, and is used to coat plant seeds before sowing. The Newcastle group also developed bioinformatic systems for dissecting the bacterial genome. As part of this work, we developed novel systems for modelling bacterial cell populations, discovered fractal-like cell-cell interactions in growing populations, and developed new techniques for measuring promoter activities in situ. These innovations have been published, and have been adopted in the field. There was an unexpected difficulty in engineering additional orthogonal signalling systems for Gram positive bacteria. Instead, additional systems were developed from Gram negative bacteria. This work has spawned a whole series of experiments to create novel patterning systems, based on orthogonal cell-cell signalling. |
Exploitation Route | Our published methods for modelling and measurement of bacterial cell populations are finding use for biofilm analysis - relevant to industrial microbiology and biomedical biofilms. |
Sectors | Agriculture, Food and Drink,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
URL | http://www.haseloff-lab.org |
Description | Fernan Federici's work on the structure of bacterial biofilms and plant based host systems heavily used high resolution 3D imaging techniques. He is a talented microscopist and photographer. This has lead to a wide range of outputs - with award winning images, book illustrations, art exhibitions. Some examples of the work can be found at: https://www.flickr.com/photos/anhedonias/ and http://data.plantsci.cam.ac.uk/Haseloff/imaging/cell_images/cell_images.html |
First Year Of Impact | 2009 |
Sector | Agriculture, Food and Drink,Education,Manufacturing, including Industrial Biotechology |
Impact Types | Cultural,Societal |
Description | Advisor on Synthetic Biology to Prof. John Beddington, Government Chief Scientist. |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
Description | OECD - National Academy of Sciences - Royal Society joint enquiry in Bellagio, advisor on Synthetic Biology. |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Scientific Advisor to Synthetic Biology Project, Woodrow Wilson Institute, Washington DC, USA |
Geographic Reach | North America |
Policy Influence Type | Participation in a guidance/advisory committee |
URL | http://www.synbioproject.org |
Description | Scientific Advisor, Royal Society Synthetic Biology Policy Coordination Group. |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Scientific Advisor, Wellcome Trust Synthetic Biology Planning Group. |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Diagnostics, prosthetics and orthotics to tackle health challenges in developing countries |
Amount | £1,500,000 (GBP) |
Funding ID | EP/R014000/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 02/2018 |
End | 02/2021 |
Description | GCRF Pump-priming Fund |
Amount | £80,000 (GBP) |
Organisation | University of Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 12/2018 |
End | 07/2019 |
Description | Microsoft Research Studentship |
Amount | £70,000 (GBP) |
Organisation | Microsoft Research |
Sector | Private |
Country | Global |
Start | 10/2009 |
End | 09/2012 |
Description | Plaswires |
Amount | £380,000 (GBP) |
Funding ID | PLASWIRES |
Organisation | European Commission |
Department | Seventh Framework Programme (FP7) |
Sector | Public |
Country | European Union (EU) |
Start | 09/2013 |
End | 09/2016 |
Description | Strategic Research Initiative for Synthetic Biology |
Amount | £150,000 (GBP) |
Organisation | University of Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 10/2013 |
End | 10/2016 |
Description | Synthetic Biology Strategic Research Initiative 2016-2019 |
Amount | £165,000 (GBP) |
Organisation | University of Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 10/2016 |
End | 09/2019 |
Title | Measurement of intrinsic properties of promoters |
Description | Combined software and technical approach to reducing noise and providing accurate estimations of promoter properties in microbial systems, based on multi-parameter measurement and use of integrated models of cell proliferation and gene expression. |
Type Of Material | Technology assay or reagent |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | Being used to evaluate gene circuit components prior to assembly of elaborate circuits, e.g.: Grant PK, Dalchau N, Brown JR, Federici F, Rudge TJ, Yordanov B, Patange O, Phillips A, Haseloff J. Orthogonal intercellular signaling for programmed spatial behavior. Molecular Systems Biology 12:849-861, (2016). |
Description | Voigt, MIT |
Organisation | Massachusetts Institute of Technology |
Country | United States |
Sector | Academic/University |
PI Contribution | The collaborations with the Voigt (MIT) and Wipat (Newcastle) laboratories have resulted in exchanges of reagents, software and data - useful for the modelling and reprogramming of microbial cell populations. The Cambridge laboratory has produced CellModeller software, advanced measurement techniques and signalling genes. |
Collaborator Contribution | The Newcastle labs have shared software and data for genome-wide definition and use of Bacillus subtilis DNA parts. Newcastle and Cambridge continue to collaborate in this area through the Flowers Consortium. The MIT labs have been a source of novel DNA parts for regulation of transcription. Further, the EPSRC grant has provided a basis for extended collaboration and interaction, not the least through editorial work at ACS Synthetic Biology. Chris Voigt is Chief Editior of ACS Synthetic Biology, based at MIT, and JH is a consulting editor. |
Impact | Publication and displays of contributions to "Synthetic Aesthetics" synthetic biology project (http://syntheticaesthetics.org, and Chapter 4 in Synthetic Aesthetics, Investigating Synthetic Biology's Designs on Nature. By Alexandra Daisy Ginsberg, Jane Calvert, Pablo Schyfter, Alistair Elfick and Drew Endy. ISBN: 9780262019996 MIT Press. |
Start Year | 2009 |
Description | Voigt, MIT |
Organisation | Newcastle University |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The collaborations with the Voigt (MIT) and Wipat (Newcastle) laboratories have resulted in exchanges of reagents, software and data - useful for the modelling and reprogramming of microbial cell populations. The Cambridge laboratory has produced CellModeller software, advanced measurement techniques and signalling genes. |
Collaborator Contribution | The Newcastle labs have shared software and data for genome-wide definition and use of Bacillus subtilis DNA parts. Newcastle and Cambridge continue to collaborate in this area through the Flowers Consortium. The MIT labs have been a source of novel DNA parts for regulation of transcription. Further, the EPSRC grant has provided a basis for extended collaboration and interaction, not the least through editorial work at ACS Synthetic Biology. Chris Voigt is Chief Editior of ACS Synthetic Biology, based at MIT, and JH is a consulting editor. |
Impact | Publication and displays of contributions to "Synthetic Aesthetics" synthetic biology project (http://syntheticaesthetics.org, and Chapter 4 in Synthetic Aesthetics, Investigating Synthetic Biology's Designs on Nature. By Alexandra Daisy Ginsberg, Jane Calvert, Pablo Schyfter, Alistair Elfick and Drew Endy. ISBN: 9780262019996 MIT Press. |
Start Year | 2009 |
Title | CellModeller |
Description | High performance software tool for modelling cellular behaviour in large populations, that provides a physico-genetic model. |
Type Of Technology | Software |
Year Produced | 2010 |
Open Source License? | Yes |
Impact | Cell modeller allows precise description of fractal-like cell buckling and cohort behaviour in biofilms: Rudge TJ, Steiner PJ, Kan A and Haseloff J. Cell shape-driven instability generates self-organised, fractal patterning of cell layers. ACS Synthetic Biology, 2:705-714, (2013). Rudge TJ, Steiner PJ, Phillips A and Haseloff J. Computational modeling of synthetic microbial biofilms. ACS Synthetic Biology, 1:345-352, (2012). The software has also been used to model plant cell growth and dynamics: Dupuy, L., Mackenzie, J. and Haseloff, J. Coordination of plant cell division and expansion in a simple morphogenetic system. Proc. Natl. Acad. Sci. USA 107:2711-6 (2010). |
URL | http://haselofflab.github.io/CellModeller/ |
Description | ArtCell Exhibition |
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 | Scientific art exhibit with microscopy images from Jim Haseloff and Fernan Federici, opened by the Mayor of Cambridge and open to the public. |
Year(s) Of Engagement Activity | 2011 |
Description | BBC Radio 4 interview |
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 | Interview about the potential impact of Synthetic Biology |
Year(s) Of Engagement Activity | 2010 |
Description | Cambridge Crash Course in Synthetic Biology |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Annual 2-week interdisciplinary course in Synthetic Biology for professionals and students. |
Year(s) Of Engagement Activity | 2009,2010,2011,2012 |
Description | Collaboration on Floreana, musical composition |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Collaboration on Floreana with music composer Rosalind Page as part of The Origin Cycle, an avant garde music and media piece that celebrated Charles Darwin, and incorporated plant microscopy images related to collections made on the voyage of the Beagle. The piece was performed at the Harvard Natural History Museum, Boston, and Australian Museum, Sydney. |
Year(s) Of Engagement Activity | 2009,2010 |
Description | E. chromi museum displays |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | E. chromi at the Wellcome Trust, display of iGEM biological designs for human health and new biosensors, scientific collaborator with designers Daisy Ginsberg and James King. This was followed by displays at: Design Museum, London; Museum of Modern Art, New York, and a travelling exhibition in Australia and New Zealand. |
Year(s) Of Engagement Activity | 2010,2011,2012 |
URL | http://www.echromi.com |
Description | EU 2WAYS hands-on exhibit for Synthetic Biology |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Schools |
Results and Impact | Constructed a touch-screen based interface for computer modelled growth of flowers, as part of a collaboration with Christophe Godin, Montpellier. A simple interface allowed children to explore the genetic control of plant growth and explore different floral structures. The interactive exhibit was teamed with a display board of floral architecture. |
Year(s) Of Engagement Activity | 2009,2010,2011 |
Description | Edinburgh Science Festival: Designer Life |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Panelist on public debate on Synthetic Biology, transmitted as part the "Material World" programme radio. |
Year(s) Of Engagement Activity | 2010 |
Description | Royal Society: Future Technologies |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Public discussion at South Bank, London with Sir Tim Burners-Lee, Stephen Fry, Prof. Dame Wendy Hall and Bill Thompson |
Year(s) Of Engagement Activity | 2010 |
Description | Synthetic Biology in Chile |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Participation in a public workshop to promote Synthetic Biology in Santiago, Chile, with Profs Drew Endy and Tom Knight. |
Year(s) Of Engagement Activity | 2012 |
Description | Wired magazine interview and pictorial articles |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Published interview about Synthetic Biology and article about engineering living systems. "Building new life forms at the iGEM Jamboree", and "At home with the DNA hackers". |
Year(s) Of Engagement Activity | 2009 |