Pathway to Independence – an interview with Lydia Djenoune Free

Let's start at the beginning: when did you first become interested in science?

I grew up with five siblings, so my parents couldn't keep us in the house and we spent a lot of time playing outside looking at nature. That's maybe how the interest started but I never really pictured myself as a scientist. Another influence, perhaps, was when I was around 8 years old; we had a science project in my class about genetics, talking about how eye colour was defined. It was the first time I heard about DNA, and I was completely fascinated by the idea that a single gene could encode a given function.

At what point did you decide to pursue a scientific career?

As a kid, I wanted to be an archaeologist, and a cop, and a journalist – I wanted to be everything! I didn't grow up with people in academia; I just didn't know how to become a scientist. But, when I was in college, I started to understand how academia works and a PhD became the logical next step after my undergraduate and Master's degrees.

How did you decide what to study for your doctorate?

It came very organically. During the first year of my Master's degree, we had the opportunity to go abroad for an internship, and I went to Florence Marlow's lab at the Albert Einstein College of Medicine in New York, where I discovered zebrafish as a model organism. Then, for the second year of my Master's, I joined Claire Wyart's lab in Paris because she was also doing zebrafish work and was looking for students. Claire was working on spinal cord development and I was interested in neurobiology – so it was a case of being there at the right time.

What did you work on during your PhD at the French National Museum of Natural History with Claire Wyart and Hervé Tostivint?

I worked on a peculiar population of neurons located at the interface between the cerebral spinal fluid and the central nervous system, called cerebrospinal fluid-contacting neurons. The fascinating thing about these cells is that they were identified more than 100 years ago by two neuroanatomists in a lot of vertebrate species (Kolmer, 1921; Agduhr, 1922), but, for a long time, we didn't understand their function. Claire showed that these neurons were involved in locomotion. So, I set out to define those neurons molecularly. We already knew that there were two populations of these neurons in the zebrafish spinal cord, so I identified more markers to discriminate between them, and identify their specific targets within the spinal cord (Djenoune et al., 2017). I also became interested in the role of a specific channel that they express, a polycystin channel called polycystin 2-like 1 (Pkd2L1) (Djenoune et al., 2014), the type of channel that I'm still working on.

How did you come to join Iain Drummond's lab?

I considered joining Iain's lab after I met one of his postdocs who was leaving the lab, and she mentioned that he might need somebody to take over her project. Iain is a big name in the zebrafish and kidney fields, and has generated a lot of tools, so I knew of him from my PhD. I contacted him, was interviewed and then met the lab. During this process, I had the best time talking to him; he was receptive to what I was saying, and I felt that I would also learn a lot from him – I could feel right from the start that he would be a fantastic mentor. I was also looking for a more established lab, as I joined Claire's right after she started hers (I was her first student). It was amazing to get the experience of building the lab from scratch, and I am extremely grateful for this outstanding experience, but it was also quite challenging at times. I wanted to try something new by working in a more established environment.

Why have zebrafish captured your interest?

Zebrafish are very easy to use, and there are so many tools that you can use and easily generate. They're also extremely accessible; you can see everything and do a lot of work in vivo. Just 24 h after the eggs are laid, you have a little fish, which I find fascinating. Advanced genetic tools and the fact that 70% of human genes have at least one obvious zebrafish orthologue make it a great organism to model human diseases. The fact that zebrafish are genetically and optically accessible makes them a very powerful model.

How does working in the USA compare to France, both scientifically and culturally?

I find it hard to answer this question because I worked in the USA and France at different stages of my career: I was a student in the French system and a postdoc in the American one. But, culturally, everything is different in the USA! The American way of thinking is very different from the French one. As one specific example, I would say that, in France, we tend to be more straightforward, whereas, based on my experience so far, in American interactions, people might say things they don't necessarily mean to be friendly and polite, which can lead to funny, at best, or quite awkward situations at times.

You mentioned already that you took over a project from a previous postdoc. What did you work on in Iain Drummond's lab at MGH?

I worked on two projects in Iain's lab. One was modelling human mutations of renal disease using CRISPR, but I couldn't find phenotypes in the mutants I generated (retrospectively, it was probably because of genetic compensation). So I spent more time interrogating the role of calcium signalling in kidney podocyte development and glomerulogenesis (Djenoune et al., 2021).

Why did you decide to do a second postdoc with Shiaulou Yuan?

Iain decided to move the lab to the Mount Desert Island (MDI) Biological lab in Maine. My project was at a good endpoint as I'd done most of the experiments needed for a complete story – or at least a story good enough to be published (as there is always more to do!). I loved working with Iain, and I learned a lot. I'm very grateful for those 3 years and for his mentorship. Shiaulou's lab was next door to us; I was already working with him using some of the optical tools that he was developing and I was helping him with some practical aspects of starting a lab, and helping train one of his students. Once again, the transition happened very organically as it made sense scientifically. I am interested in the role of calcium signalling during development and Shiaulou was interrogating the role of intraciliary calcium signalling in left-right patterning and cardiac development, using fancy optical tools, which is something I wanted to learn how to use and develop. Using these optical tools, we recently determined that cilia are calcium-mediated mechanosensors crucial for proper left-right determination, by directly and specifically manipulating cilia (Djenoune et al., 2023), which is something that had never been done before. This stage of my career was also challenging because I ended up joining a brand-new lab once again, but this time I felt like I knew what that entailed so I just went for it.

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

From you [Alex Eve, interviewer], actually, when you told me about it last year during the Gordon Research Conference on developmental biology and sent me the information about it. I also met a fellow from last year's cohort, Leah Greenspan. She told me about all the ways she benefited from it (and I thank her again for that!), so I thought I must apply and check it out for myself.

What do you hope to get out of the programme?

I expect to learn how to package my job applications in the most efficient way possible. I've been asking different junior PIs about the best way to package the application, and they all have their own helpful answers. I'm trying to integrate all the advice, but it's very difficult to consider and implement all of it. Also, I realised that shaping an application for one market will not necessarily make it attractive for another. For instance, I think that applications for the American job market are not necessarily well received in Europe. I need help with that because most of the people I've been reaching out to are in America and trained in the USA, so I'd like to get some feedback from people who have more experience working and applying in Europe.

Where are you in the process of securing an independent position?

At the very beginning as, so far, I've only applied to one position but my goal for the upcoming year is to apply to as many as possible, as I know how brutal and competitive the market is, to hopefully get a position before next summer.

What are the most important considerations for you when choosing where to apply?

I would like to be in a place that would be attractive for trainees, especially as I have been told that it is getting significantly harder to recruit postdocs. Geographically, the USA or Europe would make more sense for me. I would love to go back home to France, although I know it's going to be hard. I am also considering staying in the USA as there are more opportunities here.

What excites you most about becoming an independent researcher?

Focusing purely on my vision and bringing together a multi-disciplinary and diverse environment. That's something that Claire and Shiaulou have achieved; their labs are quite multidisciplinary in terms of people's skills and backgrounds, and I would love to bring as many skills as possible together to tackle a question from different angles. I'm also excited about mentoring, as I benefited from the exceptional support of all my former and current mentors. Managing people is one of the aspects I find the most challenging, but that also excites me as I think that it's one of the most rewarding ones.

What other challenges do you anticipate and how will you prepare?

As a PI, you're nothing by yourself. You need trainees. Otherwise, you're not a lab; you're just a one-person entity. I'm preparing to manage and mentor a team by mentoring trainees, and also learning from what works and what doesn't work. I realise that you have to meet people halfway, and you can't expect people to respond well to your mentoring style. That's some advice I received from Iain: you cannot mentor everybody the same way, you must adapt your mentoring style to the person you're working with.

Another challenge I anticipate is securing funding and recruiting good people who you can train and learn from, and who will thrive in your lab environment. Some fellows might be the best on paper, but you might just not be able to provide the tools and the mentoring for them to be comfortable and thrive. It's something that I'm very mindful and anxious about. It's important to me to have a good environment where people feel comfortable and can explore without being afraid of making mistakes. Something hindering science is that we are always anxious about failure, but I think it's just a natural part of research. Mistakes are a luxury that is becoming harder to afford, but it's a necessary part of the process.

What questions do you want to answer in your lab?

First, just as I'm currently interrogating the role of cilia in left-right patterning, I want to interrogate the role of cilia within the heart itself. We've seen that cilia are present at quite a high density while the heart is developing but, as a heart matures, the number of cilia decreases. For a long time, it was thought that there are no cilia in the adult heart, although some recent studies challenge that assumption. There are a lot of ciliopathies associated with cardiac malformations and cardiac complications, which suggests that there is a strong role for cilia during cardiac development. I want to understand why we have so many cilia at the early stages of cardiac development, what they are doing and why they disappear after this critical time window.

I also want to explore the role of polycystins during cardiac development, as the main cause of morbidity in autosomal dominant polycystic kidney disease (PKD), which is associated with defects in those polycystin channels, is actually cardiovascular complications, not renal defects. Patients can now survive the renal complications, but there are still issues with extra-renal ones. PKD has been associated with cardiac malformations. I want to understand what polycystins are doing in the cardiovascular system and in the heart. Finally, I would also like to interrogate the role of cilia during heart regeneration later on, as there seems to be a correlation between cilia and cardiac remodelling.

In 2022, you attended a Workshop by The Company of Biologists on ‘The Biology and Physics of Left-Right Patterning’. What was this experience like?

I loved the workshop. It was very small, which really allowed everyone there to interact, which isn't something I would have been able to do otherwise. I was excited to meet the big names in the field in person and to brainstorm with them; we had many sessions where we would just discuss the next big questions, what the big limitations of the field are, what the next steps are to overcome those limitations, etc. It was also great to meet the trainees – the next generation of people who are going to tackle these questions.

Tell me more about your interest in outreach and public engagement

When I was a PhD student with Claire, she was often invited to do public outreach. I had the great opportunity to join her and go to a couple of schools to meet students from under-represented communities in science, talk to them about what we were doing, and explain the steps in starting a career in science as most students don't know what it takes to become a scientist. I've also given a couple of talks to general audiences, and participated in a couple of science fairs at the Paris Brain Institute. Similarly, I've been to some public schools in Boston to participate as a judge at a couple of science fairs. It was great to talk with students and see their excitement when they were sharing their results. Outreach is always super fun and enriching because you get the most interesting questions that you would have never thought of. Diversity, inclusion and representativity are important to me because I am from a humble background, under-represented in academia. Being of North African descent and Muslim, I see a lot of myself in those kids. I think that perhaps if they get to see that it is possible for somebody from a similar background to be a scientist, that might give them the drive to try this path if they want to, as, often, if you don't see people like yourself somewhere, you might think the doors won't open for you.

What do you like to do outside of the lab?

I used to have more hobbies before my postdoc! I like biking. I've done a couple of long bike rides: one in New York, which was about 40 miles across the five boroughs, and another one in Montreal, Canada. I also like to bake. I started to bake more often when I arrived in the USA because I was missing the French cakes and patisserie (among other things, I learned how to make macarons) and having a sweet tooth, I didn't want to develop diabetes – everything is so sweet in America!

What might Development readers be surprised to learn about you?

Today [24 June] is my dad's birthday. It's also a friend of mine, Kevin's (we did our PhD together). So, ‘Happy Birthday’ to Papa Djenoune and Kevin! It's also my brother's birthday in two days, and my mum's in four. So ‘Happy Birthday’ to Nabil and Maman Djenoune too!

Lydia Djenoune was interviewed by Alex Eve, Senior Editor at Development. This piece has been edited and condensed with approval from the interviewee.