Pathway to Independence – an interview with Girish Kale

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

Initially, especially during high school, my interests were more geared towards engineering. But then, when I was about to transition from high school to university, a new institute opened up, which nudged me in a different direction. I enrolled in a 5 year integrated Bachelor's and Master's programme at the Indian Institute of Science Education and Research in Pune, India. This programme introduced students to all major fields of science, and during the first 2 years, I became fascinated with biology, prompting me to shift my focus. This is when I truly became interested in the subject of developmental biology.

Could you give us some insight into the narrative behind your CV – how did you end up where you are today?

The first time I entered a lab was during the third year of my Bachelor's/Master's integrated programme. As part of this programme, I worked on research projects that piqued my interest in cell biology and cell mechanics, laying the foundation for my PhD project.

I joined the lab of Thomas Lecuit and became the first PhD student as part of a new research consortium, called LabEx INFORM. During my PhD, I studied cell mechanics and early development in the fruit fly Drosophila melanogaster. To be more precise, when my initial project on cell culture techniques didn't work out, I started investigating how actomyosin contractility affects cell-cell adhesion and junction remodelling with a specific focus on the protein E-cadherin.

After completing my PhD, I joined the lab of Satyajit Mayor based at the National Centre for Biological Sciences (NCBS) in Bengaluru, India, where I continued my studies on E-cadherin. The transition was smooth due to internal arrangements between the collaborating labs. While waiting for my PhD paper to be published, I secured a postdoc position at the Centre for Organismal Studies (COS) in Heidelberg, funded by a Human Frontier Science Program (HFSP) fellowship. I joined the lab of Steffen Lemke, where I am still working today.

What is your current research focus?

At the moment, my research focuses on understanding the effect of temperature on the early development of fruit fly embryos. My aim is to identify temperature thresholds that cause developmental defects. The goal is to understand the direct impacts of climate change, even by just testing the effects of minor temperature increases. In our initial set of experiments, we observed that fruit fly (in this case Drosophila melanogaster) embryos already start showing defects at 29°C, which is only 4°C higher than the temperature at which they are usually kept in our lab (Kale et al., 2023 preprint).

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

While there are studies on the effects of temperature on various stages of development, what is missing is an understanding of the cell biological basis explaining the defects that are observed. We have identified pre-gastrulation embryonic development as a stage that is particularly sensitive to temperature increases. We observe mitotic defects and are now trying to understand why mitosis is not robust and what the underlying causes may be.

For future research, I want to expand this study to include other fly species to determine if they have similar temperature thresholds and defects. This comparative approach will help identify fundamental causes of temperature-induced developmental defects. Additionally, I aim to encourage other researchers to examine if similar defects occur in their model systems.

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

The entire field of developmental biology has become much more quantitative over the past 20-30 years, moving away from its descriptive roots. This shift is particularly exciting because it allows us to put precise numbers on phenomena that could previously be dismissed as artifacts. For instance, defects in embryos exposed to higher temperatures could be easily disregarded as outliers in the past. Now, with quantitative approaches, we can measure the fraction of embryos showing defects and verify these findings through repeated experiments.

In our case, we've performed numerous experiments in which we expose embryos to higher temperatures and count the number of survivors. Consistently, we find around 15% lethality (Kale et al., 2023 preprint). In smaller experiments that require live imaging, we see defects in about 20% of embryos (Kale et al., 2023 preprint). By putting precise numbers on these observations, we can confidently identify real effects rather than dismissing them as anomalies. This shift to a more quantitative approach is one of the most exciting developments in the field in my opinion.

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

I have been applying to a handful of positions, but so far without any luck. The biggest hurdle at the moment is getting my recent work published. We are about to submit it and, once it is accepted, it will be a significant milestone. So far, feedback has been positive, with people curious about our submission and future research directions. For example, we are exploring gene overexpression to rescue defects and considering testing different genes and fly species, which opens various avenues for future research.

How did you hear about Development's Pathway to Independence Programme and what do you hope to get out of this?

I'm subscribed to the community site of Development, the Node, and receive their newsletter. This is how I initially learned about Development's Pathway to Independence Programme.

One of the main things I would like to achieve through this programme is more visibility – both for me as a researcher as well as for my work. Right now, I work in a rather small lab based at a university that not many people know about. It's always a bit surprising to me how few people work on something like the effect of temperature on (embryonic) development. To me, it feels like something really basic that more people should be working on. Ideally, I would like to get in touch with these people and together expand my field of research.

What excites (and perhaps scares) you most about becoming an independent researcher?

That's a good question. To be honest, I have sort of been independent already. Of course, my current supervisor, Steffen Lemke, is supportive and a great mentor. There's still a lot for me to learn from him, especially in terms of science communication and written communication, but I don't think becoming fully independent will be a big jump for me. I've been slowly becoming more independent and trying to be a better mentor to the students I've had so far. The tricky part might be feeling more alone because I'll be the only person in the lab – at least in the beginning.

Independence is one thing, but as an early-stage principal investigator, I imagine you feel extremely vulnerable because of all the uncertainties. It's a time in your career when everything is possible. Four or five years down the line, you might close down your lab, or 40 or 50 years down the line, you might win a Nobel Prize. Anything between these two extremes is possible. It's scary and exciting at the same time and I really thrive in this kind of situation.

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

Mentorship has various aspects, and I've been fortunate enough to have several strong mentors during my career so far, guiding the way. Also, I've mentored some exceptional students myself. In this role, I have learned that mentoring involves a knowledge transfer phase, where you teach technical skills and experimental procedures, but that the real mentorship really begins afterwards.

I've mentored four Master's students and several rotation students. My philosophy has always been to foster a synergistic collaboration, where our combined efforts yield more than we could achieve independently. Effective mentorship involves managing your time well and designing experiments that allow for dedicated time with the student. This ensures that the mentorship is productive and beneficial for both parties. In any case, mentorship not only advances research, but can be highly rewarding and important for both the mentor as well as the mentee.

You've been a preLights Ambassador for the past year, advocating the importance of preprints, open science and community building. In the role of a junior principal investigator, how would you plan to further build on these things?

I really intend to keep doing this, especially the science communication activities that I'm currently involved in. In fact, it has become an integral part of my workflow. It would of course be great if I can get students interested in doing this kind of thing as well. However, this will also depend on what kind of person they are, and what their interest are. Fortunately, I never had to defend myself for spending time on science communication and outreach.

With regard to the importance of highlighting preprints, I would just say that, as biologists, we are now all looking at them; we are all reading them. So if there is a preprint that you're going to read in detail, you may as well write an informal review or commentary on it. That's basically the thinking that drew me into working with preLights. In the future, I imagine there will be many moments when I discuss preprints with students. In these cases, I will try to motivate them to write this up and post it somewhere. It's a simple and, I think, obvious extension of what you're already doing.

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

I am part of a group of friends who regularly meet to play board games. It's been a bit difficult lately with everyone moving, but we plan to re-establish it soon. This is a passion that I might even bring to the lab once it's up and running – it's a great team-building exercise.

Another thing I really enjoy is following the International Space Station. There are various websites where you can track its current location and find out when you can see it. Especially in the early morning or late evening, it appears as a bright star moving across the sky. I try to catch a glimpse of it whenever I can.

Girish Kale was interviewed by Reinier Prosée, Community Manager of preLights. This piece has been edited and condensed with approval from the interviewee.