Transitions in development – an interview with Sonia Sen

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

I should probably first acknowledge that I wasn't aware that science interested me! I think I was much more inclined towards literature and art. But, if I think about it, many things must have fed into my latent interest in science. A big part of it must have been my exposure to the diversity of life around us. I used to go birding with my mum. We'd come back home and draw the birds we saw. My father lived in the Andaman Islands for many years. Down the hill from our house was the ocean and tidal pools, and our back door opened to dense tropical forests. I also had excellent science teachers at school. They taught in very innovative ways, always incorporating fieldtrips and little projects into our lessons. My mum was a doctor and we lived on the hospital campus with other doctors, researchers, and their families. So, I was also surrounded by conversations about medical cases and science. All of this must have contributed to my interest in science.

How did you come to do a PhD at the National Centre for Biological Sciences, India, and what did you work on?

I did my bachelor's degree in St. Joseph's College, Bangalore, where I studied chemistry, zoology and microbiology. I had a fantastic chemistry teacher, and when I realized I had to repeat a year because I'd missed two exams, I asked him if I could hang out in his lab. I had so much fun there! The lab was just starting out and there were just four of us – three PhD students and me. We had to do everything – from buying chairs, washing glassware, to planning and executing experiments. That experience made me certain that I enjoyed research. But, I think I was generally more inclined towards neurobiology than chemistry. Around that time, I attended a Winter Symposium at the CMC Hospital in Vellore. There were fantastic talks by people from all over the world. There was one session with Veronica Rodrigues and K. S. Krishnan – stalwarts in neurobiology research in India. I was particularly fascinated by Veronica's work on the development of the olfactory system in flies. I was so taken by the beautiful confocal images she showed – and frankly, by her! – that I applied to her lab. My PhD project was looking at the genetic pathways that are involved in the assembly of the olfactory circuitry. The olfactory circuit is fantastic because of its stereotypical wiring. It lends itself beautifully to thinking about how genes influence this wiring because any small perturbations are very easy to detect.

After your PhD, you worked on the flatworm for a while before starting your postdoc position at Chris Doe's lab at the University of Oregon. What was the motivation behind that?

As I was writing up my PhD thesis, I found myself confronted with how similar circuits that process visual and olfactory information are, and how very similar genetic networks seem to be involved in constructing them. I wrote about this in a review article with K. VijayRaghavan and Heinrich Reichert, who were my mentors (Veronica had since passed away). I decided I wanted to tinker with this for a while after my PhD. Heinrich used to teach at an experimental marine biology course in Roscoff, France, and I managed to get the funds to go to this course. The course was very hands-on, and we had excellent faculty who covered many marine models. I got particularly interested in the acoel flatworm, which diverged quite early, but has a well-organized, centralized nervous system. I came away from that course with the idea of seeing whether the genetic networks that patterned this nervous system along the anterior-posterior axis are the same as in other extant brains. These genomes were just coming out, and I had been reading about CRISPR and was thrilled about all the possibilities it opened up. I decided that I would take a year to work on this. Chris, to whom I'd applied for a postdoc position, and the Fulbright–Nehru Postdoctoral Fellowship, who were funding me, allowed me to defer joining Chris' lab by a year. Heinrich and the Wadhwani Foundation supported this work and I'm truly grateful for this four-pronged support that I had! I didn't get as far as I'd planned, but did manage to figure out how to introduce elements into embryos, keep them alive, and trace cells.

Could you tell us more about your work during your postdoctoral research?

Chris’ lab is known for having established how neural stem cells are patterned in time to generate different neurons. All neural stem cells go through a temporal sequence of genes and in each ‘time’ window give rise to different neural types. My PhD work had gotten me thinking that it was time to revisit another well-established idea in the field – that of spatial patterning of neural stem cells. This is because I'd found, quite by chance, that if I fiddled with a single transcription factor in a single neural stem cell, I could completely rewire the brain at any point during development. This meant that neural stem cells retained and actively maintained their spatial identity. I wanted to chase what those factors could be for all the neural stem cells in flies. I'd been reading about single-cell approaches, and thought they'd lend themselves well to this question. But, during my discussions with Chris, I realized that a more natural fit for both our interests was to think about how a stem cell reads its temporal information, in the context of its spatial information, to generate stem cell-specific neuronal identities. So, this is what I worked on during my time in Chris' lab.

In 2019, you returned to India to start your own group at the Tata Institute for Genetics and Society (TIGS). What were your most important considerations when you were looking for a group leader position?

I knew that I always wanted to return to India. I love, and have always loved, working here. My research interests were in development and evolution and, by now, I also wanted to start looking at the functional output of the nervous system – behaviour. So, I was looking for a place that had use for these diverse interests of mine. It was at that time that I visited TIGS and the gorgeous insectary that they have. I was immediately taken by mosquitoes – both their development and their behaviour. Here was another dipteran with such cool biology and such fantastic behaviours to study! And it was close enough to Drosophila that we could use our learnings in flies to chase questions in mosquitoes. I was immediately sold!

I was also thinking about what it means to be working in India. I'm always struck by the investment that went into allowing me to do what I do today. Now scale this to every practicing Indian scientist at any level. Faced with this, I can't help but think about how to pay this forward. TIGS very actively thinks about this too – what science do we do, and how it impacts our society. I really value this. So, when I'm thinking about my research questions, I'm also thinking about how I can have an impact that is broader than what we as a small group do. This could be in methods that we develop and disseminate for the research community tailored for the Indian context or it could be in developing projects that integrate with local universities and colleges that not only advance science, but also result in training large numbers of students.

Can you summarise the research themes of your group?

Neurodevelopment and behaviour are the two big themes in my group. We are studying how stem cell lineages diversify to generate different types of neurons in the brain, and, once the brain circuitry is assembled, how it gives rise to behaviour. Importantly, we're agnostic to the model organism. When we're studying behaviour, we focus on mosquitoes – Aedes, Anopheles, and we're beginning to look at Culex too – although we move back-and-forth between flies and mosquitoes. We study larval swimming behaviour and adult feeding behaviour. Our approach is to identify questions we're interested in and embrace whatever technology we need. A huge advantage of working in Bangalore is that there are many institutes and labs, and therefore diverse expertise at close call. It's a very supportive ecosystem – people are always willing to talk, share ideas and resources, give feedback, and collaborate. It's really quite wonderful to be in a place like this. At the development end of things, we primarily work with flies, but we're also exploring other systems to address questions of how you get diversity of cell types in the developing brain.

What are the current exciting areas in neurodevelopment and behaviour?

These are both such exciting fields right now! The questions we ask are fundamentally the same, but the way in which we can tackle these questions has been transformed. We can now do optogenetics and chemogenetics to manipulate the nervous system. In flies, this can be done at an individual neuron level. We can trace every connection a neuron makes and we can refer back to databases for genetic access to the connecting neurons. We can monitor activity in the entire brain while the animal is behaving. We can assess transcriptomes or chromatin of individual cells. We can manipulate genes while monitoring cell identities of entire tissues and we can do this at high spatiotemporal resolution and for the entire genome.

With all of these tricks up our sleeves now, the really important thing is how we use these techniques to address questions in a thoughtful way. It's far too easy to get caught-up in the method and lost in what it tells us!

How did you find transitioning to a group leader?

I'm loving it! I'm still learning, of course, but I've enjoyed every minute of it. It's nothing like what I expected, and most of what I do on an everyday basis is not what I've been ‘trained’ to do. But it's all deeply satisfying.

How important do you think is mentorship in navigating an academic career?

Oh, extremely important! There are obvious mentors – your PhD or postdoc advisers – and I've been serially lucky in this domain! Maybe my view of science is skewed because of this serial good luck: Veronica and Vijay, who were my PhD advisors; Heinrich, who was a collaborator; and Chris, who was my postdoc advisor. They are (were) not just great scientists, but genuinely good humans and, most importantly, always fun to work with. I've thrived on discussions with them – discussions that were stimulating and encouraging, but always challenged me. They've also been extremely generous with their time and intellect and this has continued long after I left their labs. I still bounce ideas off them and send them anything I write for feedback (and always get swift responses!).

But, I do think that mentors and mentoring also goes far, far back. It could be someone from your childhood you thought were the ‘bees-knees’ and wanted to emulate. It's teachers in school, who went out of their way to make sure you learned what you were supposed to. It's your friends who both encourage you through the slumps and call you out when you're being sloppy. All these people, who take interest in you, are really important mentors. And I've been lucky to have had many of this variety of mentors too.

What advice would you give to people starting their own labs?

I'm not sure that I am in a position to do that just yet! But, I guess the most important thing I learned (and must work actively towards following myself) is that it's important to do what you enjoy doing. The trick is to identify what one enjoys or doesn't because most of what we do is so intertwined, that delineating what's enjoyable from what's a bother is not always trivial. But, if you can do that, and you have the luxury of eliminating that source, do it! And of course, eat well, sleep well, and exercise!

How do you approach hiring new team members?

I think I've tried every single method and have come to realise the ‘success rate’ is the same no matter what I try! So, I feel like the approach to hiring is not as important as the approach you take after you hire, because each person who comes to the lab is different. I think figuring out what works between that person, you, and the lab is way more important.

How is your experience being involved with the Indian Society of Developmental Biologists (InSDB)?

I think got roped into the InSDB because of work I did with the Bangalore Developmental Biology Club, which was run by Raj Ladher (National Centre for Biological Sciences, Tata Institute of Fundamental Research), Sachin Kotak (Indian Institute of Science) and Dhananjay Chaturvedi (Centre for Cellular and Molecular Biology). During the COVID-19 pandemic the Club's meetings went completely online and we took advantage of this new format to organize a seminar series. We invited speakers from all over the world to give talks and, I must say, people were so generous with their time! This was a huge success – there were times when we had 700 people attending from all over India!

Raj was also the secretary of InSDB at the time, and the board invited me to join it. I was really pleased to see that it was a really progressive, forward-looking board. It was a mix of people in different career stages and locations, and they were very open to supporting new ideas. Coincidentally, the InSDB 2024 meeting was also supposed to be held on our campus, and I got involved in this too. So, it's been quite an active period – we redesigned our logo and website and hired a community manager, Indulekha, who's absolutely fantastic. Now that the meeting is over, we're working on ensuring that InSDB serves the community of developmental biologists at every career stage in India, current with our times.

What do you think is the role of the InSDB, and societies in general, in scientific research?

Societies have a very important role to play in research. At InSDB, we're thinking about it in three ways. First, we're of course here to serve the community of scientists engaged in developmental biology research. India is a large country, with labs dispersed in many different locations. Sometimes this can mean that you're struggling with things that someone's cracked already. It could mean that there are local solutions to reagents or instruments that you may not know of. You might be struggling with paperwork related to importing materials that others have figured out. Someone may have made a fly line, plasmid, or a bacterial strain that would save others a lot of time. We want to ensure that people, no matter where they are, have a platform to talk to each other so that they are not stuck in their research. We're also eager to support other local chapters of Developmental Biology Clubs, which are a great way to get people talking to each other.

We also want to promote the study of development at different levels. The process of development is such that many key concepts in biology can be taught through it – cell biology, molecular biology, genetics, quantitative approaches to biology. So, we're looking to work with teachers at schools and colleges to build resources that they could use for teaching parts of their prescribed curriculum, but by using examples from developmental biology. We're also going to start competitive fellowships for summer internships in developmental biology labs across India. And, finally, we're working towards building longer-term projects between research institutes and universities so that students can plug-in, carry out a set of experiments, and plug-out at the end of their short lab stint, but the project carries on for longer. This would be a great way to build up a resource that is useful for the scientific community, and simultaneously expose students to research methodology.

We also want to be a platform that can facilitate the networking between researchers and clinicians. These two groups, who are often thinking about similar problems, don't often have a common space to bump into each other to interact. So, we're working towards becoming the platform that brings the research and clinical communities together so that they can work more effectively together.

Did you ever consider an alternative career path?

That is such a long list! I wanted to do theatre, journalism, study literature, do art… at some point I wanted to be a river guide! But, on a more serious note… I feel like there is diminishingly less value in defining boundaries between subjects or streams. Today in science, if we want to get anything done at scale and effectively it can only be at the interface of many types of expertise – academia, industry, design, information technology, communication – and this is what's particularly exciting about being in science today.

Finally, what do you enjoy doing outside of the lab? Is there anything Development readers would be surprised to learn about you?

I like being out in the countryside with my binoculars and my dogs. I love to run and swim. I'm good at neither, but unless I do either one of these every day, I can't function! It's as much of an addiction as my morning coffee and newspaper. And, yes, I still get two physical newspapers delivered to me every morning!

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