Quick Chat with Professor Sébastien Rodrigue
By Emma Lindsay - APRIL 18TH 2024
Dr. Sébastien Rodrigue is a professor at the Université de Sherbrooke in the Department of Biology. His research focuses on microbial systems, synthetic biology, and genomics to understand microbial genomes and develop methods to modify them. He is also the Co-Founder of TATUM Bioscience, a therapeutic company that uses synthetic biology to develop immunotherapies.
Can you tell us about yourself and your research?
I did my BSc and PhD in the Département de Biologie at the Université de Sherbrooke. During my thesis, I was interested in understanding the full genetic program of a bacterium using Mycobacterium tuberculosis as a model. I considered cells as “living robots” that could eventually be programmed to yield better vaccines or new therapies. However, M. tuberculosis was already a complex and specialized pathogen, which directed me to search for simpler model systems that would be easier to fully grasp. This led me to start a postdoc at the Massachusetts Institute of Technology where I studied Prochlorococcus, a very abundant marine cyanobacterium with a small genome and very few transcription regulators that could potentially be hacked for biotechnological applications. Prochlorococcus was fascinating but proved to be much more difficult than I anticipated for different reasons. I developed a collaboration with Tom Knight as a side project and started working on Mesoplasma florum, which is a mycoplasma-like bacterium with an even smaller and even simpler genome of about 800kb and 685 genes. I was recruited back at the Université de Sherbrooke and decided to focus my lab on minimal genomes and synthetic genomics. Since then, my group uses M. florum but also E. coli to develop new tools and therapeutic approaches using synthetic biology.
Why did you decide to use Mesoplasma florum as a model? What made it easier to work with?
M. florum has one of the simplest genomes while also growing fast with a doubling of approximately 30 minutes. In contrast to other small genome mycoplasma, M. florum is an insect commensal that has no known pathogenic potential. It is also easy to get colonies on agar plates, which sounds straightforward, but for some bacteria like Prochlorococcus can be difficult. Overall, it was a fast-growing organism, with a small genome and a good potential to do interesting synthetic genomics projects.
What inspired you to go into synthetic biology?
I think it was the vision that cells are machines, and that if we understand them enough, we could reprogram and engineer them for various applications. I like to say synthetic biology is like studying a putative alien technology: if we had a UFO to dismantle and play with the parts, we could potentially understand it sufficiently to rebuild a flying machine or even create new technologies.
Your work consists of modifying the genomes of organisms; do you think the public has a good understanding of its applications?
No, I don’t think the public knows or understands exactly what synthetic biology is about. This can raise concerns, especially in the post-COVID era. It would be important to explain the goals of synthetic biology, the potential benefits, and the intense work on biocontainment mechanisms to ensure safety. This will be particularly important if we want to build new therapies that can treat and cure patients without any additional risk of infection. I think there will be a lot of innovation in that area in the coming years.
Where do you envision the field of synthetic biology being in the next five years?
I think we are just starting to see the true potential of synthetic biology. Most circuits that we build right now only have a few genes. This is enough for many applications, but in my opinion, we will slowly move towards more complex circuits, and synthetic genomes that offer interesting properties such as ease of engineering, modularity, genetic insulation, and resistance to viruses. I also hope it will become much cheaper to write DNA since this remains an obstacle for many projects and that we will see more real-world applications in addition to fundamental advances.
Your research can be applied to a wide range of applications such as medicine and the environment, where do you think your research will have the greatest impact?
I think at first, it will be in the medical world. Biology had most of its notorious achievements in medicine, and it is probably easier for synthetic biology to reach these applications. However, I hope that we will be able to address environmental problems. We know that climate change is a major challenge and synthetic biology has potentially a lot to offer, for example with carbon dioxide sequestration. There are also a lot of opportunities in food production. Our way of producing food contributes to and will be threatened by climate change. If we had better ways to grow our food or if we could invent new food, I think that could have a major impact. But again, people will have to understand and accept genetically modified organisms. Consumers still have the last word in the end.
You co-founded TATUM Bioscience, can you tell us about the goal of TATUM bioscience and what inspired that?
TATUM bioscience was initially started on a microbiome editing technology that could selectively and efficiently eliminate antibiotic resistant bacteria directly in the intestinal tract. However, the company rapidly pivoted for different reasons and is now creating a new type of immunotherapy to treat various types of cancer.
The main motivation for starting the company was to maximize the chances of societal impact of the technologies that we develop. We decided to be proactive and create our opportunities instead of simply hoping to potentially be noticed by pharmaceutical companies or VC funds. A crucial step was to submit patent applications whenever there was significant intellectual property to protect. We were also fortunate to be supported by the ACET National Bank incubator based in Sherbrooke and to raise funding with private investors. There are many programs to help create startups in Canada and this can be an interesting path for students interested in synthetic biology.
What advice would you give to students interested in pursuing a career in synthetic biology or related fields?
I would say that it is obviously important to master theory, laboratory techniques, and ideally bioinformatics (that’s a good tool that not enough people have) but my advice would be to cultivate creativity. Synthetic biology will reach its full potential only if we can imagine clever solutions to important problems. So, think about specific problems that you would like to solve and be creative. Then, go to your computer or to the lab and really try to change something. Another possibility that is important to consider for students is entrepreneurship. There is momentum being built in Canada for SynBio companies. Fundamental research is great, I really loved it, but another way to have an impact is to start companies and have products reach the market. I hope that many SynBio students will be interested in that possibility and that they will start companies. I have done it with a former PhD student and a colleague, others can do it too!
Dr. Sébastien Rodrigue’s work in modifying microbial genomes highlights the potential of reprogramming living systems. Looking ahead, he strives for the expansion of complexity, affordability, and safety in the synthetic biology field. Based on his experience with TATUM Bioscience, he hopes to inspire students to do the same, fostering innovation and driving progress in the field.