Synthetic Biology for engineering plant growth

Synthetic Biology is an emerging field that employs engineering principles for constructing genetic systems. The approach is based on the use of well characterised and reusable components, and numerical models for the design of biological circuits.

We have constructed a series of tools for controlling gene misexpression and marking specific cells in growing plants. We are building a new generation of genetic circuits that incorporate intercellular communication, and could be used to generate self-organised behaviour at the cellular scale. These can be used to reprogram plant development and morphogenesis. We have chosen Marchantia polymorpha as a simple model system for understanding and engineering plant growth. This lower plant provides unparalleled benefits in ease of culture, simple genome, haploid genetics, open form of development and rapid growth and regeneration, and is an ideal partner for modern quantitative analytical tools.
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Open positions in Cambridge

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There are 5 positions open in our laboratory - to work on various aspects of biology and engineering in the Marchantia system. They provide excellent opportunities for anyone interested in learning how to use this new platform for plant biology. The positions are:

OpenPlant Research Associate in chloroplast synthetic biology. Appointment until the end of Mar 2021 in the first instance. Will work on the development of new tools for engineering chloroplast transformation and gene expression in the model plant Marchantia
http://www.jobs.cam.ac.uk/job/25917/ (closing date 19-Jun-2020)

BBSRC Research Associate in plant synthetic biology.
http://www.jobs.cam.ac.uk/job/25918/ (closing date 22-Jun-2020)
BBSRC Research Assistant in plant synthetic biology
http://www.jobs.cam.ac.uk/job/25919/ (closing date 22-Jun-20)
3 year appointments. The appointed team will help characterise and exploit a full collection of synthetic promoters derived from transcription factor genes in the Marchantia genome. These provide a comprehensive set of markers for mapping cell interactions during development.

NERC Research Associate in Plant Bioelectronics. (18 mo full-time, or part time up to Jan 2023. http://www.jobs.cam.ac.uk/job/25920/ (closing date 22-Jun-2020)
NERC Laboratory Research Technician. (2 year full-time appointment)
http://www.jobs.cam.ac.uk/job/25948/ (closing date 22-Jun-20)
The team will conduct research using miniature bioelectronic sensors implanted into plant tissue, and measure the state of the surrounding soil using plants as in situ chemical laboratories. Small low-cost sensors, including implanted electronics and regenerative coating will be screen-printed, and directly grafted into plant tissues.

Recent publications, events and resources

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Systematic Tools for Reprogramming Plant Gene Expression in a Simple Model, Marchantia polymorpha.
The OpenPlant toolkit is a set of interlinked resources and techniques to develop Marchantia as a simple testbed for bioengineering in plants, with techniques for simple and efficient axenic propagation and maintenance of Marchantia lines with no requirement for glasshouse facilities. Marchantia plants spontaneously produce clonal propagules within a few weeks of regeneration, and lines can be amplified million-fold in a single generation by induction of the sexual phase of growth, crossing, and harvesting of progeny spores. The plant has a simple morphology and genome with reduced gene redundancy, and the dominant phase of its life cycle is haploid, making genetic analysis easier. We have built robust Loop assembly vector systems for nuclear and chloroplast transformation and genome editing. These have provided the basis for building and testing a modular library of standardised DNA elements with highly desirable properties. We have screened transcriptomic data to identify a range of candidate genes, extracted putative promoter sequences, and tested them in vivo to identify new constitutive promoter elements. The resources have been combined into a toolkit for plant bioengineering that is accessible for laboratories without access to traditional facilities for plant biology research. The toolkit is being made available under the terms of the OpenMTA and will facilitate the establishment of common standards and the use of this simple plant as testbed for synthetic biology.
Systematic Tools for Reprogramming Plant Gene Expression in a Simple Model, Marchantia polymorpha. Susanna Sauret-Güeto, Eftychios Frangedakis, Linda Silvestri, Marius Rebmann, Marta Tomaselli, Kasey Markel, Mihails Delmans, Anthony West, Nicola J. Patron, and Jim Haseloff, ACS Synth. Biol. 2020, 9, 4, 864–882 (2020).
Click here to download PDF
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DNA methylation in Marchantia polymorpha
Methylation of DNA is an epigenetic mechanism for the control of gene expression. Alterations in the regulatory pathways involved in the establishment, perpetuation and removal of DNA methylation can lead to severe developmental alterations. Our understanding of the mechanistic aspects and relevance of DNA methylation comes from remarkable studies in well‐established angiosperm plant models including maize and Arabidopsis. The study of plant models positioned at basal lineages opens exciting opportunities to expand our knowledge on the function and evolution of the components of DNA methylation. This Tansley Insight summarises current progress in our understanding of the molecular basis and relevance of DNA methylation in the liverwort Marchantia polymorpha. Adolfo Aguilar‐Cruz, Daniel Grimanelli, Jim Haseloff & Mario Alberto Arteaga‐Vázquez New Phytologist 223(2):575-581 (2019)
Click here to download PDF
Synthetic Biology initiatives in Cambridge
We help to organise a range of Synthetic Biology themed initiatives that promote interdisciplinary exchange between Biology, Computer Sciences and Engineering in Cambridge though informal meet-ups, forums, project-based training and shared research projects.
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SynBio IRC: Maintains an online clearing house for information about synthetic biology research at the University of Cambridge. http://www.synbio.cam.ac.uk
OpenPlant:
Research centre to promote open technologies for plant Synthetic Biology. https://www.openplant.org
Biomaker: Project funding for construction of low-cost devices for biology. For more information see: https://www.biomaker.org
Caf
é Synthetique: Monthly meeting for networking and building interdisciplinary links. http://www.meetup.com/Cambridge-Synthetic-Biology-Meetup
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Our No-Code Programming Workshops, Biomaker Challenge and Open Technology Week are running again in 2020-2021. These events support interdisciplinary training and projects that promote a maker ethos in science and sharing of open source software and hardware systems, graphical programming, 3D printing technologies and open biological tools. We have now expanded with international teams. More details can be found at www.biomaker.org.
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See a compilation of Biomaker projects (as well as online tutorials) at https://www.hackster.io/biomaker/. The Hackster platform allows self-publication of materials lists and "how-to-build" instructions for hardware projects. Also download our No-Code Programming Handbook at: https://www.biomaker.org/nocode-programming-for-biology-handbook
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Cambridge CODE (Centre for Organismal Design and Engineering) project is an initiative that brings together biologists, engineers, physicists, mathematicians and computer scientists to tackle the challenge of engineering of growing cellular systems, genome engineering and redesign of organisms. Details of the plant effort can be found at: https://www.plantcode.org
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Scientific themes in the lab

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2020-2021: Haseloff Lab research projects
The lab hosts undergraduates for research projects in the Department of Plant Sciences. Students may be taking the third year of their Natural Sciences Tripos (Part II) or fourth year of a Master's Degree in Engineering. Students will have a day-to-day supervisor, and projects are generally customised for the individual, but a list of broad areas of interest can be found here. Please contact Prof. Jim Haseloff for more detailed information.
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Synthetic Botany
Plants modular and plastic body plans, capacity for photosynthesis, extensive secondary metabolism, and agronomic systems for large-scale production make them ideal targets for genetic reprogramming. Christian R. Boehm, Bernardo Pollak, Nuri Purswani, Nicola Patron, and Jim Haseloff. Cold Spring Harbor Perspectives in Biology: Synthetic Biology 1-19, (2017). Click to download PDF
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OpenMTA: Opening options for material transfer
The Open Material Transfer Agreement enables practical, broader sharing and use of biological materials by biotechnology practitioners. Linda Kahl, Jennifer Molloy, Nicola Patron, Colette Matthewman, Jim Haseloff, David Grewal, Richard Johnson & Drew Endy. Nature Biotechnology doi.org/10.1038/nbt.4263, (2018). Click to download PDF
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Loop assembly: a simple and open system for recursive fabrication of DNA circuits
Loop assembly is based on a recursive use of two Type IIS restriction endonucleases and corresponding vector sets to enable efficient assembly of large DNA circuits. Bernardo Pollak, Ariel Cerda, Mihails Delmans, Simón Álamos, Tomás Moyano, Anthony West, Rodrigo A. Gutiérrez, Nicola Patron, Fernán Federici and Jim Haseloff. New Phytologist, 222: 628-640, (2019). Click to download PDF
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Design of low cost reactors for molecular diagnosis and bioengineering
An international Biomaker Expert Group is tackling the design and construction of air-driven, temperature-regulated incubators for low-cost diagnostics and synthetic biology research. For information at:
https://www.openplant.org/blog/2020/5/11/design-of-low-cost-reactors-for-molecular-diagnosis-and-bio-engineering
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μCube: A Framework for 3D Printable Optomechanics
An assembly standard for the production of 3D printed optical devices -basis of a framework for parametric design of modular mounts for generalised design of modular optical devices following this μCube standard.M Delmans, J Haseloff. Journal of Open Hardware 2:1-9 (2018). Click to download PDF

Tools for macrophotography of liverworts in the field

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Lunularia cruciata liverwort plant photographed in situ, using a Panasonic GX80 camera, Olympus 60mm macro lens, 10mm extension tube and Raynox DCR-250 macro lens adapter. Technical details at: https://www.hackster.io/jim-haseloff
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Jim's hints: camera systems suitable for field work and documentation of small plants in the field. Camera setup and modification for high-speed, handheld focus stacking - including a comparison of the new Olympus TG-5 camera, modification of the Panasonic GX80 camera, and choice of a tripod that is well-suited for macrophotography of small plants, like bryophytes. More technical information at: https://www.hackster.io/jim-haseloff/

Resources

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Lab publications
Find a list of published papers and patent applications from the lab compiled here. These can be downloaded directly as PDFs.
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Teaching materials
Updated and new reference materials, including lecture notes, slides and PDFs can be found for courses on Origins of Agriculture (NST PMS 1B), Plant Development (NST CDB 1B) and Synthetic Biology (NST PS 2), taught by Jim Haseloff at the University of Cambridge.
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Images of liverworts in the field
See photo galleries of plants from the Australian Bryophyte Workshop in the Flinders Ranges
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Microscopy image galleries
Navigate to the Imaging index page to find different galleries of microscopy images. These include a wide range of historic plant samples that have been collected at the Department of Plant Sciences in Cambridge, where conventional cytological stains are often highly fluorescent and reveal new features when imaged using modern multispectral confocal laser scanning microscopes.

OpenPlant Handbook

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An introduction to OpenPlant, objectives, work programme and summary of recent progress. The Handbook also contains thumbnail sketches of OpenPlant researchers.
Download PDF version of Handbook (15 MB, 170 pages)
Download Bakubung Report Capacity Building for the Bioeconomy in Africa (3.9 MB, 26 pages)
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Working in Cambridge
There are open positions in the plant synthetic biology group. Please contact Jim Haseloff (jh295 at cam.ac.uk for more details).
The best place to find general information about postgraduate study at the University of Cambridge is the Graduate Admissions site. This includes customised links to potential funding sources for UK and international students. For information about synthetic biology research projects in the Haseloff Lab at the University of Cambridge, click here.