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.

Publications

10 25 50
 
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 Participation in a national consultation
 
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 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 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 advisory committee
 
Description Scientific Advisor, Wellcome Trust Synthetic Biology Planning Group.
Geographic Reach National 
Policy Influence Type Participation in a 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