by Steven Burgess
We are going to hear a lot about genetic modification of plants over the next year as governments seek to update regulatory frameworks. Additionally, 2016 is the first time the annual synthetic biology competition iGEM will be accepting entries specifically focused on plant synthetic biology. We therefore thought it would be a great opportunity to run a series of articles and interviews that explore what is meant by ‘plant synthetic biology’, how it is unique, what challenges it faces, and how these findings could potentially impact upon other strands of synbio. In this first part, I look to provide an overview of the topic.
“Can you appreciate the beauty of a flower?“
– it is not a question you would expect a scientist to ask. But then again, Richard Feynman was not your typical scientist.
A Nobel prize winning physicist and bongo player, Feynman was also a great communicator. Out of the many entertaining quotes and anecdotes from his life, the clip about beauty is perhaps my favorite. I include it here, as it brings together the two topics I want to discuss: plants, and Feynman’s infectious approach to science.
This is because disrupting natural systems and analyzing the effect underpins most research in biology, but when scientists try to use this knowledge to control development or metabolism, it often becomes apparent that there are large gaps in our understanding. By building biological systems ‘bottom up‘, it is possible to identify where these gaps are – and this is where synthetic biology comes in.
How do you make a plant?
– is a question that has interested scientists for some time, and with technological advances it is one we might soon be able to answer. The production of ‘minimal organisms’ is one strand of synthetic biology research, March saw the unveiling of ‘Synthia 3.0’ – a synthetic bacterium that possessed a ‘minimal genome’ containing only 473 genes – all of which were essential for life.
Fun stat:@Gen9Bio could synthesize JCVI-syn3.0 (minimal genome = 531,000 bp) for $15,930. We've crossed the "crappy car" price threshold.
— Maxx Chatsko (@MaxxChatsko) March 24, 2016
In comparison, the smallest known genome of a photosynthetic organism belongs to the prokaryotic, unicellular cyanobacterium Prochlorococcus, which has just 1,716 genes (it is likely that the number that are essential for survival is significantly lower).
However, this is way before we can start talking about eukaryotic algae, let alone plants. Even for minimal bacterium Synthia 3.0 we don’t know the function of ~150 of the ‘essential genes’, and comparative genomic analysis identified that there are at least 311 nucleus-encoded proteins of unknown function that are conserved in plants and green algae, and are absent from non-photosynthetic organisms – there are a lot of gaps to fill.
What is Plant Synthetic Biology?
If you are unsure what synthetic biology is, a rough explanation is that it borrows ideas from engineering to make biological manipulation easier (there are some helpful videos online). If this sounds confusing, a comparison drawn from the industrial revolution might help illuminate what this means.
Up until the mid 19th century, each screw was made by the work of a blacksmith, resulting in a high degree of variation, the effect of this – you had to scrabble around trying to find the exact screw to fit your hole. As you can imagine this didn’t make mass production easy.
It wasn’t until advances in manufacturing allowed Joseph Whitworth to introduce a standard screw design that automation and the advantages it brings ushered in the modern world. In biology, most genetic modification is currently carried out by individual researchers in an artisanal fashion – we are essentially at the stage of blacksmith manufacture, and as a result biotechnological development can be slow, and suffers from many problems of reproducibility.
To address this problem a lot of effort in synbio research is currently going into identifying and characterizing different biological parts (promoters, UTRs etc) that can be assembled together in order to control gene expression, metabolism or development in a predictable manner (a good recent review focused on plants can be found here). This is analogous to the way in which standard screws are used with other standardized materials to build more complex structures.
All of this is true for plant synbio too, but working in plants brings a number of distinct challenges and advantages.
Why Bother Doing ‘Plant’ Synbio?
“The imagination of nature is far, far greater than the imagination of man.” – Richard Feynman
For pollinators the attraction to flowers lies in iridescence, the same phenomenon that causes the shimmering color of soap bubbles.
Surprisingly, floral iridescence is not created by pigments, but is actually dependent on diffraction of light as it hits the grooved surface of the petals. This is just one of many, many examples why shape is important in biology, and scientists seek to understand these structures by recreating them in a process dubbed ‘synthetic morphogenesis‘.
Complex 3D structures are only possible in multicellular organisms. Plants are both multicellular and sessile, meaning they are fixed in one place, and unlike in metazoans, cells do not migrate during development (as seen for example in neuron migration, or Zebrafish embryos).
This makes plants an ideal biological system with which to design, build and test genetic circuits to recreate the 3D structures seen in nature, and the OpenPlant‘s favorite bryophyte Marchantia polymorphia is being developed as a model system for this purpose.
This is a topic we will return to later, but a lot of effort has gone into modifying crops to improve pest and herbicide resistance, salt tolerance, and increased yields. Advances in gene editing technology make it possible to speed up the rate of variety development.
— Valencia UPV iGEM (@UPVigem) June 26, 2016
Major plant engineering initiatives have started to adopt approaches from synthetic biology, including C4 rice, Realizing Increased Photosynthetic Efficiency (RIPE) and Engineering Nitrogen Symbiosis for Africa (ENSA) projects, all of which are taking different approaches to increase the yield of crop plants.
Agriculture provides a well established system for the production and processing of vast quantities of material. To capitalize on this, plants can be genetically engineered to produce chemicals, vaccines or antibodies in a process know as ‘Pharming‘.
There can be significant cost benefits to using plants for production when compared to traditional fermentation technology. There are instances where this could be an advantage, for example, the production of the anti-malaria drug artemisinin was recently demonstrated in tobacco, and this could provide a cheaper alternative to yeast based synthetic product which has been a commercial failure.
When we talk about manipulating plants for pharming or agricultural purposes there are many societal factors which need to be considered. Modification of plants can be a particularly emotive subject, and failures to take into account consumer choices could have an impact on uptake.
Whether creating genetically modified (GM) plants is necessarily the best option to address a particular challenge should be scrutinized with the same scientific rigor as is applied to fundamental research. Additionally the potential impacts of diverting agricultural land away from food production to vaccines or drugs must be carefully considered.
GM will never be the only solution to addressing a problem, and often there are many other approaches which could be adopted first. However, it could play part in combined efforts along with social, economic and political efforts to meet the challenges of food security and environmental protection.
“The more I ask why, the deeper a thing is, the more interesting it gets” – Richard Feynman
If we ask why are bees attracted to flowers? It leads to the question how do petals generate iridescence? If we continue probing we might ponder why the surface of petals is grooved? Then we can keep going – we know that some butterflies are also iridescent, so is this effect created in the same way? are the same types of molecular interactions underpinning this process?
If we keep probing we will discover more of nature’s secrets, what Feynman teaches us is that if we can’t reproduce what we can see, we might not appreciate its full beauty.
I want to thank Cameron Tout for his suggestions. Additionally I provide the following disclaimer – I work in collaboration with members of the OpenPlant project and have received money to fund a mini project from the Cambridge Synthetic Biology Strategic Research Initiative so I have a vested interest in plant synthetic biology. Additionally I am employed on the 3to4 project which investigates C4 photosynthesis for translational purposes. All opinions stated are private and not representative of PLOS.