Pathway to Independence – an interview with Thomas Juan Free

Let's start from the beginning, when did you first become interested in science?

I became interested in science from an early age and I have always wanted to become a scientist. One of my first memories about science is from a summer course that I went to at the age of seven, where we had to pick fossils in the mountains. Since then, I never lost interest in fossils and natural sciences. I still look for fossils in the mountains to this day.

You did your PhD at the Institut de Biologie Valrose (iBV) with Maximilian Fürthauer. What did you work on?

I ended up in the lab of Maximilian Fürthauer working with zebrafish by serendipity. I was still waiting for answers from other grants to work on cell culture models when I was offered a PhD position in the Fürthauer lab, which I accepted. It turned out to be a very good experience. I started working in the lab in 2013, at the very beginning of the CRISPR revolution. At that time there was just one paper on zebrafish using CRISPR/Cas9. My PhD supervisor put this paper in my hand and asked me to replicate it for the project that was ongoing in the lab, on a novel regulator of cilia function in zebrafish. Unfortunately, the mutant I created using this new technology did not recapitulate the morpholino-induced phenotype described previously in the lab, which led me to change my topic after two years. I then switched my focus and became interested in left-right asymmetry establishment later on during my PhD (Juan et al., 2018).

What made you decide to join Didier Stainier's lab for your postdoc?

As I mentioned, the beginning of my PhD suffered collateral damage following the integration of the novel CRISPR technology. One of the main zebrafish labs working with the CRISPR technology and showing how to interpret the phenotypes it triggers was the Stainier lab. I got inspired by his description of a genetic compensation mechanism taking place in mutants, but not in morphants (Rossi et al., 2015), later termed transcriptional adaptation (El-Brolosy and Stainier, 2017). Didier Stainier is also famous for his pioneering work on cardiac development, a blood flow mechanosensitive process. After working with left-right asymmetry, established through flow mechanosensation, I got the opportunity to explore other types of mechanosensitive processes in Didier's lab.

What are you currently working on?

My main project, published at the beginning of the year (Juan et al., 2023), is about the description of multiple mechanosensors important for cardiac valve development. Currently, I am finishing the revisions of another paper on the control of cardiac contractions using Cre/lox and degron technologies in zebrafish. As a follow-up, I am developing a new project on the function of blood flow mechanosensors not only in cardiac valve development but also in the cardiovascular system in general.

How was the move from France to Germany, from your PhD to your postdoc position?

Administratively, the move was smooth, because moving from one European country to another is relatively easy. Scientifically, it was a bit of a culture shock as I came from a very small lab during my PhD, and moved to the giant lab of Didier Stainier, with more than 50 team members. I had to adapt to this new environment and gained a lot of autonomy to achieve my goals. I kept the same model organism, the zebrafish, but moved from studying the left-right organizer to the heart.

How did you hear about Development's Pathway to Independence Programme and why did you decide to apply?

I found out about it on social networks like Twitter. In parallel, my postdoc supervisor Didier Stainier suggested the programme to me, as he knew that I was applying for positions at that time.

What do you hope to get out of the programme?

I hope that the programme will help me improve my group leader applications and provide me with better visibility in my field. I have already benefited from several aspects of the programme and have discussed with my mentor, Ken Poss, how to approach institutes as a zebrafish PI applicant. I am also hoping to receive more feedback on my research proposals, as well as how to set up a lab and select group members.

Where are you in the process of securing an independent position and what has your experience been so far?

I have been applying for 6 months now. The standards for becoming a group leader have increased a lot in the past decade. Scientists used to secure positions much earlier during their career and competition is stronger than ever. I am getting better opportunities and invitations to present my work since June, as my second postdoc paper is in the process of being published. I am hopeful that I will find a position by the end of the year.

What excites you most about becoming an independent researcher?

I am excited about being able to lead fully my research. I am already very independent in Didier's team, where I have supervised several students and led my research projects autonomously. I am now ready to go to the next level as an independent group leader.

And conversely, what do you think will be the most challenging aspect of being a PI and how will you prepare for it?

Becoming a PI can look overwhelming from a postdoc's perspective. As a future PI, I am concerned about creating a good organization system and stress-free environment for my lab members. Dealing with administrative and management duties, as well as teaching responsibilities, requires a lot of adaptability, which I acquired during my postdoc.

What are the factors that you're considering when you look for where to start your own lab?

I am flexible geographically in Europe, but I am looking for a dynamic and connected city. As a zebrafish cardiovascular biologist interested in flow mechanosensation and genome engineering, I am looking for an institute matching this profile.

What research questions would you like to address with your own group?

I am interested in fundamental questions associated with blood flow mechanosensation and the creation of genetic tools. So far, I have focused on cardiac valve development, and I plan to expand this expertise to the rest of the cardiovascular system. I will focus on the role of blood flow in the development of other types of endothelial cells, such as the venous, arterial and blood-brain barrier populations. I will investigate how the blood flow shapes and maintains the identity of these different cell types.

In your opinion, what are some of the most exciting advances in your field?

The study of biological flow mechanosensation is a very active field, mostly driven by researchers working on the cardiovascular system, the central nervous system and the left-right organizer. There has recently been a couple of very interesting papers presenting new technologies that will probably become future standards. For example, the Vermot lab showed that the response to blood flow mechanosensation is almost instantaneous, after observing calcium elevation in mechanically stimulated areas using high-resolution 4D imaging (Fukui et al., 2021). A piezo-based mechanosensor (Yaganoglu et al., 2023) has recently complemented this calcium-based mechanosensor, adding more to the researchers’ toolbox. In addition, two studies focused on the left-right organizer showed that flow mechanosensors are located in spatially restricted areas of cilia, opening new avenues in the field of mechanosensor imaging (Djenoune et al., 2023; Katoh et al., 2023).

How important do you think mentorship is in navigating an academic career? Have you had any important mentors in your academic career?

Having a good mentor is crucial to setting someone on the right path in a laboratory. My PhD mentor Maximilian Fürthauer provided me with a set of tools and a strong organizational system that are very important for early career researchers. Young researchers are not often provided with clear guidance on how to record experiments or take care of lab stocks and are rapidly overwhelmed. As a mentor myself, I now like to provide my students with a strong organization system on which they can rely.

I also learned a lot from my postdoc mentor Didier Stainier, who leads such a big team while being available for most of our enquiries. I appreciate how he found a balance between getting involved in every project of the lab, and not being overwhelmed by all the problems arising in a lab of this size.

You mentioned several times about having a good organizational system in the lab. What have you done to improve efficiency in the lab?

My PhD supervisor has strong organizational skills and I was inspired by this. I learned programming to create custom-made software to make the lives of lab members easier. For example, I created what I call the primer blast software, which allows people to blast a sequence onto the stock of primers, to prevent re-ordering. During my PhD, I was also disturbed by the fact that fish facility recording was carried out manually. I then created a fish management software for small-sized fish facilities called ZebraFile, currently in use by five labs. During my postdoc, I created another software, called BadBench (to sort your badly organized bench) to manage and store lab stocks of all sorts. My philosophy is that when somebody takes more than five minutes to find something, organization needs to be improved.

Finally, is there anything Development readers would be surprised to learn about you?

I am originally from the South of France and the place I come from is very rich in fossils. I am passionate about fossil hunting, palaeontology and human evolution in general. I was inspired by the work of Svante Pääbo, who received the Nobel Prize in Physiology or Medicine in 2022 for his pioneering work on Neanderthal genome sequencing. Although I did not follow a career in palaeontology, one of my career dreams would be to take on ancient genome projects using my favourite model, the zebrafish, in the field of cardiovascular development. I am always open to collaborations!

Thomas Juan was interviewed by Joyce Yu, Online Editor at Development. This piece has been edited and condensed with approval from the interviewee.