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International Symposium on Synthetic Biology in Toulouse, France (Part 2)

Samir Hamadache - December 25, 2018

The second day of the EUSynBioS Symposium this past October was jam-packed with presentations from senior scientists and students from all over, including Canada. Here, I summarize some of the sessions I attended. (read about Day 1 here)

SynBio Society Consortium: an international commitment to collaboration

With the international expansion of synthetic biology research, there is an opportunity for synthetic biology societies to learn from and collaborate with one another. Over lunch on the second day, we discussed some first steps for launching an international SynBio Society Consortium and potential opportunities for collaboration. Following the consortium, we produced a joint statement to assert a commitment to collaboration:

SynBioS - towards stronger international connections in synthetic biology

Accompanying the establishment of synthetic biology as a discipline, the past five years have seen many local, national, and supranational synthetic biology groups founded around the globe. United in the aims of promoting synthetic biology research as well as professional and policy development, the associations can benefit substantially from forging and maintaining strong horizontal connections.

On October 23rd, representatives from six national and supranational synthetic biology associations - EUSynBioS (Europe), SynBio UK (United Kingdom), GASB (Germany), SynBio  Australasia (Oceania), SynBio Canada (Canada), and EBRC SPA (United States of America) came together at the 2018 EUSynBioS Symposium Toulouse to set the foundation for a new international collaborative effort, the SynBioS Consortium. The representatives introduced their history, activities, and future plans through short presentations and discussed various topics of mutual interest, such as funding, social media, and science policy.

Concluding the workshop, the representatives confirmed their interest in continuing discussions as part of the future SynBioS Consortium, which will include regular online meetings focused on exchanging advice, coordinating initiatives, and reviewing progress.

We are looking forward to advancing synthetic biology together and encourage other national synthetic biology associations to join our endeavour.

~ EUSynBioS, SynBio UK, GASB, SynBio Australasia, SynBio Canada, EBRC SPA

 Standards in synbio, a new carbon-source for E. coli, and virtual organisms

Dr. Manuel Porcar (University of Valencia, Spain) kicked things off Tuesday morning with an overview of the opportunities and challenges surrounding standardization in synthetic biology. While universal synbio “parts” would be ideal to make designing gene circuits easier, Dr. Porcar highlighted that living systems are so diverse—even within the same species—that standardized synbio parts may not turn out to be as convenient as we’d like. In fact, most parts used by iGEM teams are new to the competition’s registry. Dr. Porcar pointed out that, so long as evolution is in the picture, standardizing parts for use in natural environments is futile, since the parts will naturally change over time. On the other hand, he suggests that parts could be standardized for specific chassis (host organisms) used in the lab for particular functions. For example, D. radiodurans is the go-to microbe for work involving strong radiation. He also discussed BioRoboost, a new project funded by the EU with 27 partners from Europe, North America, and Asia, aimed at finding an international consensus on defining biological standards.

Rational design and directed evolution are two techniques that synthetic biologists use to generate new biological systems: the former involves modifying or recombining biological parts from nature, and the latter involves randomly mutating genes and selecting for desired traits. From Génomique Métabolique in France, Dr. Volker Doring presented work directing the evolution of E. coli strains to produce amino acids from formic acid. Formic acid is a single-carbon compound that can be made from CO2, and so this is a valuable opportunity for biofuels and environmental remediation. In the same issue of ACS Synthetic Biology, Dr. Doring’s team also published a rational design approach to obtain the same outcome, showing that new carbon-uptake systems can be produced using both directed evolution and rational design.

Rationally designing metabolic pathways is a daunting task that Toulouse-based start-up company iMEAN is making easier using virtual organisms. To close the morning session, Dr. Lucas Marmiesse, Co-Founder and CTO, presented their company, which specializes in in-silico models analysis. Using their extensive database of gene-regulatory and metabolic networks, they create millions of “virtual organisms” that can produce a client’s desired metabolic product. Using an artificial intelligence algorithm, they identify the best design to recommend for experimental validation. iMEAN aims to simplify the design phase of large-scale projects for synthetic biology companies and researchers.

Noisy genes, metabolic engineering, and building a bioeconomy

When a gene is expressed into a protein by a cell, there are several steps that depend on random events taking place, like the right proteins finding the start of the gene on a DNA molecule. These random events result in fluctuations in the rate of the protein being produced, and this variation is known as gene expression noise.

Dr. Fabien Duveau, at Université de Paris Diderot in France, has been studying the effect of expression noise on the evolutionary fitness of cells sharing the same environments. Dr. Duveau’s research team has developed a library of yeast strains with unique mutations to the promoter of the TDH3 gene, a gene that is known to affect fitness depending on its noise level. The different mutations result in different levels of noise in the TDH3 gene, as well as different average levels of expression. Then, they compared the growth rates of these different strains. They found that when the average expression level was close to optimal for survival fitness, more noise resulted in slower growth; but when the average expression is far from the optimum, noisier expression was advantageous. In other words, when the expression of an important gene like TDH3 is much higher or lower than needed, more noise means that more cells will express the gene at levels closer to optimal, helping them grow faster.

Dr. Max Mundt, at the Max Planck Institute for Terrestrial Microbiology in Germany, is also studying gene expression noise and has developed an effective tool for precisely tuning the noise and average expression level of a gene. Being able to control expression noise is important in order to study its role in natural biology or to reduce uncertainty in synthetic systems. Their system works by allowing the experimenter to control two steps in gene expression: transcription of the mRNA intermediate, and its degradation. His team then tested this system on the mating pathway of yeast, where he was able to finely tune the noise of SST2, a key regulator of the mating behaviour.

Dr. Lorie Hamelin presented on the opportunities and challenges of a bioeconomy-based future.

Dr. Lorie Hamelin presented on the opportunities and challenges of a bioeconomy-based future.

Gene expression noise is not the only thing synthetic biologists want control over. Dr. Olivier Borkowski and his team at Microbiologie de l’Alimentation au Service de la Santé Humaine in France are studying the impact that expressing foreign genes has on a cell’s physiology and how the cell responds to this burden. Being able to understand this is important for the design of predictable systems and to have greater control in engineering them. After identifying key genes that are involved in the cell’s burden response, Dr. Borkowski’s team constructed a genetic circuit that is regulated by this response itself, so that the cell only expresses synthetic genes if it doesn’t compromise its own growth. This presents a useful tool for ensuring that engineered cells maintain a healthy level of growth while expressing synthetic genes.

A few presentations in this session focused on developing microbes that can produce valuable compounds or break down harmful ones. Dr. Danai-Stella Gkotsi, at the University of St. Andrews (UK), has identified and tested new halogenases—enzymes that add halogens to molecules at specific positions. At the University of Queensland in Australia, Dr. Konstantinos Vavitsas is enhancing the potential of cyanobacteria to produce terpenoids, compounds that are of value to industries such as nutraceuticals and biofuels. He presented his team’s successful production of the antimicrobial terpenoid isopimaric acid in the leaves of a tobacco plant. Dao Ousmane presented a project by his iGEM team at Paris Saclay called MethotrExit: an E. coli based “cleaning factory” for removing the anti-cancer drug methotrexate, a harmful cytotoxic chemical found in hospital wastewater.

The last presentation of the night came from Canadian scientist Dr. Lorie Hamelin, who works at the Biological Systems and Processes Engineering Laboratory in Toulouse, where she is focused on the need for sustainable and environmentally-friend food production solutions for the world’s rapidly growing population. This summer, she was awarded President Macron’s Make Our Planet Great Again grant to lead a team on CambioSCOP, a five-year project that she proposed, aimed at building a sustainable, circular bioeceonomy in France and transition to a decarbonized economy. In her presentation, she highlighted the energy and agriculture challenges of sustaining a massive world population and the need for sustainable synthetic biology solutions that do not create novel environmental problems of their own.

We ended the night with an insightful panel discussion with Drs. Olivier Borkowski, Jean Marie François, Lorie Hamelin, and Pierre Monsan. The title of the discussion was “Towards a Circular Economy”, and the panelist touched on subjects including sustainability, ecological footprints, and academic career advice for young researchers.

It was a great pleasure to attend the EuSynBioS Symposium and to meet scientists and like-minded students from all over the world. I look forward to seeing where the SynBioS Consortium takes us in the years to come!

The last event of the Symposium was a panel discussion on establishing a circular economy based on synthetic biology. Featuring Drs. Jean Marie Francois, Lorie Hamelin, Pierre Monsan, and Olivier Borkowski

The last event of the Symposium was a panel discussion on establishing a circular economy based on synthetic biology. Featuring Drs. Jean Marie Francois, Lorie Hamelin, Pierre Monsan, and Olivier Borkowski

Samir Hamadache