Since the discovery of the fundamental laws of inheritance in pea plants byGregor Mendel at the end of the XIX century, researchers all over the world have been investigating the secrets hidden in the DNA of plants and inventing/improving techniques that transformed the way in which humans grow green organisms for agricultural or industrial purposes – such as the green revolution that relied on the use of semi-dwarf and high-yielding varieties that doubled cereal production in the 1960s or the use of genomics tools in modern breeding and plant pharming (i.e., the use of plants as factories to produce pharmaceuticals.
To learn more about emerging fields in Plant Science, BotanyOne met Dr. Jae-Seong Yang and Dr. Ivan Reyna-Llorens, two young group leaders at the Centre for Research in Agricultural Genomics (CRAG, Barcelona) who organized the Plant Synthetic Biology conference in September 2022.
What, exactly, does Plant Synthetic Biology mean?
Jae-Seong and Ivan coincide in the definition of Plant Synthetic Biology – Plant SynBio in short – as the next generation of plant biotechnology and genetic/metabolic engineering. Ivan explained that this evolution was made possible by new technologies (e.g., Next Generation Sequencing and genome synthesis) as well as new tools that facilitate the generation of hundreds of different constructs using automated systems and robotics.
Jae-Seong specified that Synbio applies the concepts and principles of Engineering to biology: DESIGN-BUILD-TEST-LEARN (and back in a cycle).
Initial experimental DESIGN: definition of the biological problem to be addressed and selection of potential organisms, pathways, and tools to be used. BUILD: synthesis and assembly of the molecular components needed to modify the selected organism. TEST: validation of the experimental design through screening, genotyping/phenotyping and molecular/biochemical analyses of the modified organism. LEARN: data analysis and modelling, gathering of new information to redesign experiments. Adapted from: Petzold et al., 2015. Credits, MO (Canva)
Ivan told us that Plant SynBio aims to use these principles and technologies to improve or solve many of the problems we currently face in terms of biodiversity, food security, sustainability, and health. Jae-Seong added, “Compared to previous approaches, Synbio is faster”. Nowadays, that’s an advantage because, for example, traditional methods used for the genetic improvement of plants (to increase productivity or confer stress tolerance) are too slow to keep up with the fast pace of climate change. Synbio is also more drastic: considering gene transformation, the classical biotechnological approach relies on the modification of a plant with a single gene, whereas a Synbio approach introduces a set of genes (that can also come from other organisms).
Let’s talk about the scientists … why did you decide to get into SynBio and how are you developing your career in this field of research?
Ivan is a Mexican scientist who first heard about Synthetic Biology when he was a PhD student at the University of Cambridge (UK). While attending a conference by Jim Hasselhoff and Tom Knight, he was amazed by the potential of biological systems to make things that otherwise couldn’t be possible. After his PhD at Julian Hibberd’s lab, he tried to get more involved in the field and he decided to continue with a postdoc in the same group working on the C4 RICE project – a Bill and Melinda Gates initiative that aims at engineering a Rice plant that can perform the highly efficient C4 pathway. Afterwards, he got involved in the Open Plant Initiative, in which researchers from different institutions (the University of Cambridge, The John Innes Centre and the Earlham Institute) worked together on synthetic biology and evolution for improving photosynthesis. After working as a bioinformatician as part of the ENSA project that aims at using biological nitrogen fixation to sustainably increase yields for small-holder farmers in Africa (https://www.ensa.ac.uk/), he joined CRAG in September 2021 to start his own research group in Plant Synthetic Biology and Photosynthesis.
Jae-Seong is a Korean scientist passionate about computational biology. He worked as a postdoctoral researcher at the Centre for Genomic Regulation (CRG, Barcelona) in a top-leading group specialized in bioengineering in bacteria (e.g., modification of secreted proteins in the genus Mycoplasma). in September 2019, Jae-Seong swapped from bacteria to plants when he started his own group dedicated to the study of gene regulation in microalgae (i.e., unicellular photosynthetic micro-organisms). Specifically, his group works with Chlamydomonas to investigate the effect of mutations in promoter regions (i.e., DNA sequences found upstream of gene bodies that modulate transcriptional activation or repression of a given sequence encoding a protein) on gene expression. Data gathered in the lab are then computed and used for modelling expression levels of genes of interest in microalgae.
Jae-Seong finds that Chlamydomonas is an almost perfect system, between fast-growing bacteria and slow-growing plants. It can also be easily exploited as a biofactory to produce molecules of pharmaceutical interest, given that its production can be scalable – from small flasks in the lab to significant volumes in the industry.
However, the mechanisms that regulate gene expression are more complicated in eukaryotes than in bacteria (such as complex interactions among factors, chromatin remodelling, interplay of promoters with enhancers and terminators, etc) and the expression of an exogenous gene depends on the context (known as Positional effect) as it is randomly introduced in the genome.
Let’s talk about the conference… Why did you decide to organize this conference?
With the incorporation of young researchers (Jae-Seong, Ivan and recently Robertas Ursache), a previous research programme changed to become the “Plant Synthetic Biology and Metabolic Engineering” pillar. Ivan declared “We wanted to organize this conference as a way to reach out with other Plant Synthetic Biologists with the prospect of establishing new collaborations and also to promote debate about the use of Plant Synbio to the wider scientific community”. As a matter of fact, the meeting was co-organized as a joint initiative with researchers of The Cluster of Excellence on Plant Sciences (CEPLAS) , a leading centre located in Germany, that will be hosting next Edition in 2024.
Can you tell us which were the most exciting findings presented at this conference?
Ivan thinks that the discipline of Plant Synthetic Biology has really matured, and this is reflected by the amazing talks and posters presented in the conference. Especially, he got very excited about the accessibility of technologies for the community. Jae-Seong also agrees that the development of novel tools (such as the generation of Standard cassette for MIX & MATCH) makes it easier to exchange materials among members of the scientific community.
Considering the fast moving of this field, which will be the achievements in the next 5 years? And future challenges?
In Ivan’s opinion, Plant SynBio will be facing two main challenges. The first one is the fact that biology is complex and noisy; therefore, plant scientists should keep learning about not only biology but also noisy biology. “We are still far from understanding exactly how systems work and how to stabilize the traits we want to engineer so that they are not affected by noise or by the forces of evolution. This is a challenge if we want to engineer a novel pathway into a plant, for example. As one of the speakers said, Noise is a problem for engineering but in biology noise is there to stay so we better learn how to deal with it”.
The second challenge, and probably the most important one, relates to the legal aspects and ethical issues of Plant SynBio such as the acceptance of genome editing in crops, which will play a key role in the generation of more research lines. Jae-Seong is also concerned about ethical concerns and fears arisen from novelties, but he highlighted also the benefits of these new approaches for sustainable agriculture. For example, results of ongoing research on gene regulation will allow to design ad-hoc regulatory sequences not only in the model plant Arabidopsis thaliana but also in major crops such as tomato and sorghum.
What is the impact of Plant SynBio on the society?
“The impact of this new field of research on society can be enormous. These technologies promise to change the way we manufacture raw materials, we produce food or even medicines” concluded Ivan.
“We can improve plant production of vitamin E, an antioxidant molecule that protects tissues from damages caused by high light or soil salinity” added Jae-Seong.
Of course, this is no silver bullet and as with any other technology it has its limitations. It is important that scientists and the general public are involved in the debate.
Are we ready for the next green revolution?