OpenPlant Forum 2018: Engineering Plants for Bioproduction

Blog post by Dr Colette Matthewman

Over the past decade, synthetic biology has focussed much of its effort on microbial chassis as platform for bioproduction. The single cell simplicity and rapid life-cycles of these organisms, the prevalence of biological tools and the existing industry infrastructure for fermentation have made microbes a tempting playground for synthetic biologists wishing to make a range of chemicals and biomolecules, from flavours and fragrances to distributed manufacturing of highly complex metabolites for medicine, and an increasing number of companies are finding success in this arena (e.g. Ginkgo Bioworks, Amyris, Evolva, Antheia).

More recently, plants have been showing serious promise as viable production platforms for complex chemicals and biomolecules which in many cases simply can’t be made in single celled microbes. This year, the OpenPlant Forum explored some of the latest advances in plant bioproduction with inspiring talks from invited speakers and OpenPlant researchers highlighting a promising and exciting future for plant synthetic biology.

OpenPlant post-doc Ingo Appelhagen presents his work on anthocyanin pigment production in plant cell cultures.

The first morning of the Forum focused on tools for refactoring regulation and simple test platforms for plant synthetic biology. Prof. Ian Small (University of Western Australia) opened the meeting with a keynote on the potential for using engineered RNA bonding proteins to control organelle gene expression. OpenPlant PI, Prof. Paul Dupree described research in his on engineering of polysaccharide structures in plants. We also had the first examples of plant production platforms: Dr Ingo Appelhagen presented his recently published work on the production of colourful anthocyanin molecules in plant cell cultures, while Dr Eva Thuenemann introduced the HyperTrans system developed in the Lomonossoff lab at the John Innes Centre for the transient expression of proteins in Nicotiana benthamiana, a wild relative of tobacco. Eva is working on plant-based production of a protein that could be used in a vaccine against East Coast Fever, a devastating disease in cattle in Africa. The HyperTrans platform is used by the Lomonossoff lab and recently established company Leaf Expression Systems to produce therapeutic proteins and virus-like particles for vaccines, including recent work on a new vaccine for the eradication of Polio.

The afternoon session explored the cutting edge in production of complex plant-derived natural products in yeast, with a keynote from Prof. Christina Smolke (Stanford University), followed with an insight into the engineering of triterpene production in N. benthamiana by Dr James Reed in the Osbourn lab (John Innes Centre), recently reviewed in Plant Cell Reports. These projects rely heavily on chemical and enzymatic biodiversity in nature. Dr Sam Brockington (University of Cambridge) talked about harnessing the global network of botanic gardens for access to plant diversity for metabolic engineering and synthetic biology, introducing a global database of living plant, seed and tissue collections called “Plant Search” – a perfect sedgeway into a panel discussion on Harnessing Global Biodiversity where Sam was joined by Dr Nicola Patron (Earlham Institute), Mr David Rejeski (Environmental Law Institute), and Dr Jenni Rant (SAW Trust). The discussions ranged from public opinion on synthetic biology (explored through the Global Garden workshop) and benefit sharing and dematerialisation, through to how blockchain (like the bitcoin) is being used in environmental contexts and whether blockchain technology trends can be applied to create/assign value for biodiversity.

Prof. Ralf Reski with his moss bioreactors

Day two of the Forum continued on a theme of “Tools for Metabolic Engineering” with Prof. Claudia Vickers (University of Queensland) opening by introducing the Future Science Platform in Synthetic Biology that she leads at CSIRO, as well as numerous tools developed in her research lab. Claudia was followed by a trio of OpenPlant postdocs describing analysis to unravel the genetics of divergent metabolic pathways in Brassicaceae (Dr Zhenhua Liu), a search for new synthetic biology tools based on diversity of natural triterpene oxidation (Dr Michael Stephenson) and tools for engineering Marchantia’s chloroplasts (Dr Eftychis Frangedakis).

Moving on from the tools, we explored further plant-based bioproduction platforms, starting with an inspirational keynote from Prof. Ralf Reski (University of Freiburg) on the moss Physcomitrella patens that Ralf’s lab has established as a production platform for biopharmaceuticals, leading to foundation of the company Greenovation, which produces moss-aGal (agalsidase) for the treatment of Fabry disease, a rare but painful and potentially deadly disease. Subsequently, we heard from Prof. Alison Smith (University of Cambrige) about “Designer algae” and work towards predictable metabolic engineering in microalgae, and from Dr Eugenio Butelli (John Innes Centre) about the Tomato as a biofactory for making health promoting flavonoids.

The Forum was wrapped up for this year with a session on Sharing and Techno-Social Platforms, with an introduction from OpenPlant’s Prof Jim Haseloff, followed by Dr Linda Kahl (BioBricks Foundation) on the latest with the Open Material Transfer Agreement (Open MTA) which has been developed in collaboration with OpenPlant to enable sharing of DNA parts (publication coming soon!). Next up, Dr Joanne Kamens from not-for-profit plasmid distribution company, Addgene, revealed the freshly launched plant resource page and spoke about the upcoming adoption of the Open MTA as an option under which plasmids can be shared. Finally, Dr Richard Sever from bioRxiv spoke about preprint opportunities for synthetic biology.

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Join us in Cambridge for the OpenPlant Forum 2019 | 29 – 31 July

Save the date!

[Closes 14 September 2018] Technologist in DNA packaging and delivery in Edinburgh

This position is within Prof Alistair Elfick lab, School of Engineering and UK Centre for Mammalian Synthetic Biology (www.synbio.ed.ac.uk) 

The Role:

An important underpinning technology for synthetic biology is the synthesis of DNA. Technology has now advanced to the point where it is possible to affordably construct very large constructs up to chromosome scale. An emergent bottleneck is the delivery of this into the cell. The Technologist will be actively involved in contributing to the standard development programme of the UK Centre for Mammalian Synthetic Biology (UK-CMSB), in collaboration with the National Physical Laboratory. They will be primarily responsible for delivering technologies to achieve the packaging and non-viral delivery of large DNA constructs into mammalian cells, with their reduction to practise as standard protocols. Their secondary role is the support of collaboration with academic and research staff and students of the UK-CMSB. The post holder will ensure that the development of UK-CMSB technology standards supports and keeps pace with the research requirements, liaising with industry, collaborators and users, advising and training staff and students.

Fixed term for 2 years

Grade 7

Closing date Sept 14th 2018

Vacancy reference www.vacancies.ed.ac.uk  search for #044849

Contact Alistair.elfick@ed.ac.uk for further information

The Mad Hatter's Tea-party at Boomtown

Following last year’s success at BoomTown Fair, we returned, alongside the SAW Trust, with an Alice In Wonderland themed delight for the senses, with science, art and writing activities to excite young minds.

Table laid and ready for the first guests to arrive!

Now in its tenth year, BoomTown Fair attracts up to 60, 000 people and many of those came to visit us at Kidztown, with its impressive visual displays and interactive activities for families. 

Our stand entitled “The Mad Hatter’s Tea Party” revolved around workshops which had four stations for the children to rotate around. The tea parties began with the mad hatter revealing secret invisible ink messages to the children before the experiments could begin!

The children were tasked with many exciting science-based activities. Tasty treats the children could create included sweet, fizzy sherbet and rapid ice-cream made using an endothermic reaction and flavoured with plant flavourings (vanilla, coconut and strawberry). In addition to these, there were also many pigment-based activities inspired by all the bright colours in Wonderland, for the children to try. Including; natural plant pigment tissue tie-dyes and colour changing flowers and celery. The results of which decorated the tent throughout the weekend.

Carrying on with our use of plant products, the children also got to create their own fruit flavoured jelly balls, using alginate gelling agent, derived from algae, to go with a fizzy drink!

The final activity for the children was to write secret messages, which would be revealed by a new set of children, at the next tea party by the Mad Hatter.

Some of our tea-party guests about to make sweet treats.

As well as the tea parties, there were also numerous activities and challenges for the children to engage with while the table was re-set. These activities included using microscopes to explore the microscopic world Alice enters when she shrinks, writing nonsense poems, like those the Mad Hatter recites at his tea party and pinning the grin on the Cheshire cat.

We had a range of craft activities available, providing the children with something to take home with them from their time at BoomTown. The children could make Wonderland inspired flower faces, clock necklaces, a Mad Hatter’s Hat and playing card bowties.

Across the three days the children were able to immerse themselves in a Wonderland of science, art and writing, feeding their curiosity with a range of thrilling experiments and allowing their creativity to run wild with exciting craft projects.

A big thank you to the entire team who helped with the preparations and running of “The Mad Hatters Tea Party” and to BoomTown for having us once again!

By Shannon Woodhouse

An internship with the SynBio 4 Schools project

PhD student Camilla Stanton spent a three month internship, from May to August 2018, working with OpenPlant to build resources and materials for the Synthetic Biology for Schools (SynBio4Schools) project, funded through the OpenPlant Fund scheme. In this blog post she describes the project and the work that she completed during her placement.

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Synthetic biology brings together researchers from a broad range of backgrounds to solve biological problems through rational design. While synthetic biology is increasingly being taught in universities, it remains under-represented in the national curriculum and teaching resources for GCSE and A-Level students. The SynBio 4 Schools project aims to solve this problem by creating a comprehensive educational resource package that teaches the principles of plant synthetic biology through practicals and case studies.

SynBio4Schools activites and write-ups on display at the OpenPlant Forum, Norwich, 2018

I got involved with the SynBio 4 Schools project through a 3-month industrial placement as part of my PhD. My role was to assess and identify what resources could be included and to begin compiling them. An obvious starting place was to explore the activities and demonstrations that researchers in Norwich and Cambridge had already developed and tested. While these resources are valuable on their own, bringing them together creates a set of interlinked resources that support one another, greatly increasing their reach and impact. It is also an exciting opportunity to get contemporary research into schools, helping inspire the next generation of biological engineers!

During my placement, I worked in collaboration with researchers to discuss ideas for how their research could be used in a teaching-style activity, whether that be an experiment, worksheet or craft-based. We also had discussions about what sort of supporting material might be useful, such as articles, interviews or case studies. It was a really enjoyable process as it gave the scientists a unique opportunity to think more creatively about their work, and I got to hear some really innovative ideas for teaching some quite complex concepts.

Some of the 3D printed virus structures from Roger Castells-Graells' OpenPant Fund Project.

I ended up focussing on writing up three activities based on work carried out by Dr Paolo Bombelli (plant microbial fuel cells), Dr Nicola Patron (genetic circuits) and Roger Castells-Graells (virus structures), which I was lucky enough to showcase at the OpenPlant Forum. This gave me the chance to receive feedback from other researchers and educators about how the materials could be made more accessible for students and provide more support for teachers and technicians. These suggestions helped shape the basic write-up template, which now includes additional investigations, sources and links to other experiments. 

This was a hugely valuable experience for me - I got to explore new topics, meet people with exciting and original ideas and even got to try my hand at some design work! Although I’m now back doing my PhD, the SynBio 4 Schools project definitely doesn’t end there - we want as many people as possible to get involved.

Currently, there is a growing list of activities that cover a variety of topics from plant natural products to computational biology. But we want to showcase even more research from Norwich and Cambridge! If you have developed a resource that you would like to see included in the SynBio 4 Schools project, or you think your research could translate into an educational setting, please do get in touch! Email Colette.Matthewman@jic.ac.uk

MRes Biotechnology and Biodesign

University of Newcastle are offering a new MSc program in Biotechnology and Biodesign. The course provides a foundation into how design and engineering approaches are used in the creation of new biotechnological processes and products.

More information and to apply>>>

About this course

Advances in biotechnology, computing, and laboratory automation are being coupled with design thinking approaches to engineer biological systems that may produce more sustainable products than traditional manufacturing. Examples include:

• the production of synthetic meat substitutes
• dairy-free milk
• adaptive building materials
• petroleum-replacement products
• designer antimicrobial compounds
• smart drug delivery systems

Our Biotechnology and Biodesign MRes:

• provides a foundation in design thinking approaches
• covers recent developments in applied biotechnology
• provides an opportunity to develop and refine your laboratory skills
• provides the opportunity to develop your own research project

The training forms an excellent foundation for students opting to follow a research orientated career path and for those looking for successful careers in the biotechnology industry.

The course is interdisciplinary. You'll be suitable for this course if you are:

• a science graduate
• looking to develop your knowledge and research skills

You'll gain the skills allowing you to address critical global challenges in:

• sustainability
• food security
• the environment
• healthcare