Srinath Krishnamurthy: “You may not have the resources to answer a question, but you definitely have the resources to ask the question”

🕒 27 min

Today, it is my pleasure to present another Presenting Alumni interview, this time with Srinath Krishnamurthy. Srinath was a project leader at the Summer School of Science in 2018, where he held a biochemistry project alongside his wife Sindhuja. He is in his final year as a postdoc in biophysics, working with membrane protein complexes.

Let’s start things off a bit differently. Introducing yourself is always quite difficult, so let me be more precise in guiding you: if you had to introduce yourself to someone new, what would you hate to leave out?

One of the things I really value from my life is that I’ve moved around a lot. I usually like to bring that up one way or another because it tells people that, no matter their background, I will make an effort to understand their point of view. To put it in better words as an introduction, I was born in India, grew up in Indonesia, went back to India, did my PhD in Singapore, came to Europe… I moved around a little bit. I counted once, I believe I went to ten different schools in my twelve years of schooling. The key thing I like to bring up is that, because of that fact, I’m more interested in and accepting of people’s differences.

That’s a lovely trait. You mentioned you lived in several places while growing up. Are there any stories from those years that you recount as especially formative?

So, I have a younger brother, who’s very close to me. We’re two years apart and I was always seen as the nerdier one and he was the sportier one – we played the same sports and everything, the only difference was that I wore glasses. And that was it, I became the nerdy one and he became the sporty one. I was really unhappy when I first got glasses, I was maybe six or seven years old. I think my aunt or my mother cheered me up saying that glasses were the first step towards becoming a scientist. Obviously, I hope that isn’t the reason I became one, but I do remember that incident. I also used to read a lot – nothing impressive, I would read very age-appropriate books – but that was another “scientist” activity, I was told.

You also said you liked sports. Which ones? What else did you like doing as a kid?

Yes, I also played sports a bunch. Like I said, we moved around a lot. We first lived in this small town in central India. My parents used to move often because my father’s job took him to various places. From there, we moved to Jakarta, the capital of Indonesia, which is a massive city, a true megapolis. There, the first sport I took up was badminton, which is the national sport of Indonesia, so we did really intense training.

We then moved to a tiny village in the middle of the Indonesian rainforest. The local school had maybe forty students total, so my class was maybe four or five people. Living there was amazing, there was a rainforest behind my house. I once lost my flip-flops in quicksand there. You know how, when you’re a kid, quicksand seems like this really dangerous thing? Well, I once got my foot trapped in it (even though it was really just a puddle) and I ran back home, the full length of the forest, shouting about how I’d almost died in quicksand. My mother later came with me and shook her head when she saw the puddle was so shallow I couldn’t even fit my head in there. There were lots of little memories like that, which made it really fun. However, because it was so remote, it didn’t have any badminton courts, so I had to switch sports. I chose tennis because racket sports seem interchangeable at that age. We went back to Jakarta two years later and I switched back to badminton again. I also took up football for a while – basically, my parents really made an effort to get my brother and myself tired out by the evening so we wouldn’t make too much noise.

In terms of other interests, my mother tried to get me into music, but it wasn’t something I could respect at a young age. Sitting inside in the middle of the afternoon while all the other kids were outside just didn’t sit right with me. It took me ages to get into music myself, well into my twenties. All on my own, though, I don’t really enjoy the structure of music education.

It is interesting that you didn’t enjoy structure or indoor activities, considering most people’s view of science is as a very structured, (mostly) indoor activity. Do you generally dislike structure in learning?

I do agree that sometimes structure curbs creativity, but I believe a combination of free and structured learning is best. You need to start with one and eventually transition into the other. Say you start leaning on your own. Whatever it is, you tend to hit a ceiling you cannot get past without proper training. If you go too far into structure, it almost becomes a chore, which makes you hit a different kind of ceiling entirely – you don’t enjoy it anymore. It’s worth noting that today it is much easier to learn things on your own than it was before. However, when you eventually get to the point where your own knowledge simply isn’t enough, coaching is the next step. I do love that nowadays you can find the answer to whatever you want. Even if you’re ten years old and have some silly question, you can search it up on your own. You don’t even have to get the right answer, though – the search is the fun part, isn’t it?

Education and career

You seem to have had a bunch of different interests. Was there anything specific that guided you to choose one over the others?

Most decisions on what you want to do happen at specific points in your life. When you go into high school, you have to decide roughly on the field you would like to pursue. But in India, at least when I was growing up, you had to pick STEM. That was considered to be the appropriate interest for a good student. This made that first decision an easy one.

When it comes to university, the climate was fairly similar. If you wanted to do an undergraduate course in India, you had to take engineering because there were very many good options. The good science courses were far too competitive because there weren’t as many of them, which I know has changed since I was applying to universities. But I really liked biology. That made me consider medicine instead, but that is an even more ridiculously competitive field. I was nowhere near the level I needed to be to get in. So, I took industrial biotechnology, which starts as an engineering course but also has a focus on biology. Actually, at that time, there were a lot of water issues around where I lived, so I wanted to help with that somehow. The course I chose would set me on the right path to do that. However, once I got into it, a couple really nice professors opened my eyes to the intricacies of their subjects and they got me hooked on the science of it all.

• High school: 2003 – 2005, Bharatiya Vidya Bhavan, Coimbatore, Tamil Nadu, India
• B.Tech in Industrial Biotechnology: 2005 – 2009, Alagappa Chettiar College of Technology, Anna University, Chennai, Tamil Nadu, India
• PhD in Biochemistry and Biophysics:  2009 – 2014, National University of Singapore, Singapore
• Research Fellow: 2014 – 2015, National University of Singapore, Singapore
• FWO MSCA Research Fellow: 2016 – 2019, Biophysics of Membrane protein complexes, KU Leuven, Belgium
• Current: 2019 – present, Research Fellow, Biophysics of Membrane protein complexes, KU Leuven, Belgium

Can you point out something particular that led you to that decision?

In my first year of university, I was not a good student. To put it bluntly, I didn’t really care because it was still mostly engineering topics. In my second year, there was a really nice professor who taught organic chemistry. One of the first things he said when he came into the class was a phrase that really affected me – in fact, I used it as the beginning of my statement of purpose when I was applying to PhD programs later on. It was that, “in the toolbox of life”, there are only twenty amino acids, which govern the chemistry of life. Of course, there is a lot that goes along with this, but the statement still stands. All of biochemistry is based on twenty molecules, and the really fascinating thing about them is that there isn’t anything extremely special about them. Another thing was that, for instance, if you wanted to catalyze some reaction, you might need insanely high temperatures and pressures – or you could get an enzyme to do it. It does it at room temperature and normal pressure. That really blew my mind. It made me want to study the chemistry of life.

Considering you were originally intending on going into a more practical field, how did you decide to apply for a PhD? Can you describe the experience?

There was a little bit of peer pressure. Because of my parents’ wishes and my colleagues, my options were between doing a master’s and doing a PhD. Since I had completed a four-year program, I could go straight into doing a PhD in the US or Singapore. A lot of my friends were going to Singapore, plus that would place me closer to my parents, who were in Indonesia, so I thought I would try it. I did some projects to bump up my CV, which I had quite a lot of fun doing, and ultimately got the opportunity to pursue a PhD in Singapore. It was actually very lucky that I got in because I was nowhere near the top of my class, I was mostly average. I thought I would apply for a master’s and then transition to a PhD because of that, I believed the entry criteria would be easier to fulfill that way. Luckily, the two professors who I was applying to from the National University of Singapore were doing a recruitment in India, where they came for a conference – so I knew exactly what to talk to them about! They convinced me to apply for a PhD instead.

In Europe, you would join a lab doing a particular project. In Singapore, you join a graduate program and do so-called rotations, where you spend time in two to three labs for several months. You’re doing coursework and teaching undergraduate students at the same time. So, I had joined the graduate program and a couple labs. Joining labs was an interesting process. One PI didn’t even talk to me about the science, just the number of hours they wanted me to complete per week, which was a bit off-putting. I ended up joining a very small lab led by a professor who had joined the department only two years before I did. He gave a presentation explaining his work, which got me interested because I was familiar with the instrumentation methods the lab was using. He was surprised that I liked doing the sort of work he could offer me! I joined for a rotation and it ended up being a great match.

I’m very glad. What was the instrument you mentioned? I believe you are still working on a similar thing now. Could you tell us a bit more about it?

The specific aspect of protein science I work on is called biophysics, which tries to understand molecular processes from a physics perspective. My expertise is in a technique called structural mass spectrometry. There is an instrument called a mass spectrometer, which allows you to measure the mass of your chosen compounds. This is actually how they check the contents of your bag when they swab it during airport security checks, they are looking for traces of certain compounds, usually explosive materials, by checking their mass.

We can use this instrument to measure the mass of proteins. The other thing we can do is use that to find the mass of an enzyme, a catalytic protein, which tells us about its shape about its shape, in certain cases; or we can start doing chemical modifications to the protein and change its mass, but cognizant of its shape. Whenever we start talking about the shape of a protein, we’re talking about structure. The structure of a protein defines its function. When you mess up the shape, you also mess up its ability to do its job. We see this in neurodegenerative diseases, when misshapen proteins start to clump together into what we call plaques. This is just one example. A lot of effort, time and energy in contemporary biology is devoted to understanding the shape of proteins.

This has various applications. For instance, we can think about viruses. One of the things a virus has to do is pack in its genetic information, which isn’t a simple thing. The RNA or DNA is so tightly packed that you actually need to apply force to achieve this. Now, how do you apply force on nanometer scales? There are proteins that perform this job by quite literally shoving in the genetic material. They actually have to apply enormous amounts of pressure to do this. The process is entirely mechanical, even though it’s fueled by chemical energy. The main takeaway is that proteins don’t just sit in place, they have to move to perform their function – they are dancing. This molecular dance is what I study. We use chemical labelling to understand how proteins are structured and how they move. Labels change the mass of the protein depending on a lot of factors. You can imagine how a chemical label would have a much easier time finding an “in” with a protein part that’s moving a lot, which changes the mass drastically. On the other hand, parts that are so tightly packed that the label cannot get through won’t have their mass change at all. We vary the changes and put all this information together to understand how proteins move when they function.

It sounds like very interesting work. While you haven’t veered too far from what you were doing during your PhD, you did move quite far from Singapore, all the way to Belgium. Can you tell us what brought you to the position you are at now?

When I finished my PhD in Singapore, I was getting sort of restless. I wanted to go somewhere else. This was also guided by the fact that both I and Sindhuja, my wife, who had completed her PhD around the same time, wanted to go to science hubs. We thought that would give us the best shot at doing compelling work instead of having to compromise. Our options were basically Europe or the US. Those would give us the best balance of comfort with English and developed science centers. Most of the positions I was interested in were in Germany, the UK and Belgium. I interviewed with a few people and ultimately felt a really nice connection with my current mentor. He seemed to truly respect and understand where I was coming from and my ideas. This was the biggest contribution towards my final decision, which is why I ended up choosing Belgium.

What sort of work were you looking for while applying?

I wanted to look at more complex systems. I was especially interested in a particular class of molecules called membrane proteins. They aren’t swimming around in solution, but they are actually embedded in different layers of cell membranes. That exponentially increases the complexity. The lab I was joining had an established membrane system. They had studied a lot of the biology already, which allowed me to go in and do biophysics without having to do a lot of basic microbiology, which I don’t find nearly as interesting.

I believe a lot of people might find your work very compelling, but also quite foreign. Most high schoolers don’t get taught too much about this unless they do it themselves. Is there a selection of books or other materials you would recommend for finding out more about proteins or something more specific to what you do?

I could suggest a few. One book that you could get started with as early or as late in your education as you want is Bill Bryson’s Short History of Nearly Everything. That one is great for all sciences – if you’re curious, read it. There is another book that inspired me when I was younger, and that is Survival of the Sickest by Sharon Moalem. The concept is that the parasites that infect us evolve along with us to continue to be able to infect us. For example, the cold virus sits in the upper respiratory tract and releases irritants that make you start sneezing. So, you have effectively been hijacked by a tiny thing with no brain to be its vehicle. There are many other examples that blew my mind, so I would really recommend it. Another book, one I wish I had gotten the chance to read a long time ago, is The Gene by Siddhartha Mukherjee. It introduces the field of molecular biology in beautiful writing, the prose itself is very nice. Those seem like a really nice start.

Wonderful, thank you! Before we move on, how would you say your PhD and your postdoc compare? Is there anything you wish you knew while doing your PhD that you learned only later? Or, alternatively, is there anything you learned earlier on that has been helping you since?

I use the same technique, but the way I tackle problems is completely different. More importantly, though, when I first started my PhD, I was fresh out of undergrad and I thought I knew things. I obviously didn’t. That became brutally clear to me when I did something called a qualifying exam. Two years into your PhD, you present what you have done to a panel of PIs and your peers. If you successfully complete it, you are on your way to obtaining a PhD; if you fail, you get a master’s instead. I had done enough work, and it was good work, but I went into it with a cocky attitude. I think the panel knew that, because they asked me some really nice, tough questions. The way they phrased them needed me to think outside the box for the answer even if I knew it. I often didn’t even know how to start. At the end, the head of the panel pointed out that they had to prompt me for the answer in many cases instead of it being a free flowing discussion. I remember what he said very clearly: he said I was at the level of a technician and that, if I wanted to be a scientist, I had to do my own thinking. They let me pass, but it was a big punch to my face and exactly what I needed.

The best thing I got out of that session was a lot of humility, which I continued learning afterwards. I slowly started respecting other points of view and ways of thinking, as well as the fact that I didn’t know enough. By the time I became a postdoc, you could call me an expert in the technique I do. It wasn’t the case of whether I would learn more about the technique – it was more a case of how I would do science using that technique. For that, I had to start from the ground floor, but I wasn’t as confident as before, and I had learned to be comfortable with that. I learned to leave the ego at the door.

Thank you for sharing that story, I believe that was an important lesson to learn. Finally, is there a natural next step for you? Are you planning on staying in academia?

I have been in my current position for about five years, so I have basically collected all my data and I’m just putting out papers. I’ve only been writing this year and that is what I’m doing until December. After that, I’m quite open to anything. I have already explored a lot of my interests and so I am not too set on becoming a PI. Before COVID hit, I was a lot more sure I wanted to go down that path, but the pandemic has made me want to explore other things. I will give it a shot, see how it feels, but I’m also looking at industry and thinking a little bit outside of the box with something I have been moving towards, and that is science communication. There are many projects I have in mind that I am starting to look at, I keep thinking about the stories I want to tell. You don’t get too many opportunities to learn about proteins in particular. That sort of information is generally locked away in more complex textbooks, something a general reader wouldn’t bother to go into because it’s only for people who are actually in the field. I am thinking a lot about how to change that.

Summer School of Science

Thank you so much, your story – past, present and future – is extremely interesting. Speaking of science communication, we’ve reached the S3 portion of the interview. How did you come to join the Summer School? Was it an easy decision?

I used to work in the same lab as Nikolina Šoštarić, and we had some very nice discussions during that time. She moved to a different lab shortly after but, I think because of those conversations, ended up asking me if I would be interested in participating in the Summer School in 2017, which she was organizing. However, Sindhuja and I were getting married that summer, so I knew I wouldn’t be available. It sounded so cool, though, so I told her to ask me again next summer if the opportunity arises. That December, Nikolina wanted to talk about it again and we agreed to get a drink and talk about it. Luckily, Sindhuja happened to be in Leuven with me, so she came along. I knew I wanted to do a project about biochemistry. Sindhuja ended up giving a lot of nice ideas, she is a better biochemist than I am. And so, while we were walking back, Nikolina asked if she would be interested as well, which, of course, she was. And so we did a project in the summer of 2018.

I happened to be one of the lucky few who got to work on that project, so I obviously know what it was about. However, for those who don’t, could you briefly describe it?

The idea was based on an anecdote I told you when we first started the project. I was about six or seven and sitting outside with my siblings. My grandfather was sitting with us. He would always ask us questions, why is this, why is that… This time, it was: why are leaves green? To me, the question seemed stupid, they are green because they are green. He said there was more to it – there was something inside them that made them green. This was the first question behind the project. Now, everyone has heard of chlorophyll, but another question follows: why, then, do some leaves change color in autumn? What happens to the green?

It is a simple question, but it allowed us to explore, firstly, what the pigments inside leaves are, and then how a leaf changes from green to yellow, red or orange. Obviously, the Summer School is in summer, so we had to work around the fact that we didn’t have any leaves turning. Most of the time, I was actually surprised by how well the experiments were going, the leaves we gathered gave us the answers we were looking for. We also wanted to look at the function of the pigments we found. Again, chlorophyll is a famous one, but we wanted to look at the protein structures that surround the pigments and what those complexes do in the leaf.

Well, I can tell you the project was an awesome experience. What was it like from your end? Not just the project, but S3 in general.

Working with such motivated students in the middle of summer was really amazing. Sindhuja and I also had so much fun working on the project. We had only really tested one or two things before you guys joined us, so it was often just as surprising and fascinating to us that stuff worked as it was to you. For example, we decided to look at our samples under UV light, just for the fun of it. We had never tried that before. We never knew that it would work so well! It showed us exactly what we thought it would, which we theoretically knew but didn’t expect. I also loved it when things went wrong and we had to come up with different solutions.

Of course, as a mentor, you always had to be mentally on. The day started at 8 or 9 in the morning and ended at midnight for us, and for the duration of those ten days we had to be constantly switched on. Whenever a question was asked, and everyone asked so many amazing questions, giving a half-hearted answer seemed like a dereliction of duty. I felt I had to do it justice, which was a little bit difficult after a while, which you can definitely tell because, the further along we got in the camp, the more photos there were of me sleeping all over the place, taking naps during breaks. But really, it was even more fun because of that.

I’m sure you get an amazing bunch of students every year, but I’m even more sure that the ones who were there when I was were just phenomenal. In fact, when you guys first started asking questions about the project, Sindhuja and I were worried that it would be too simple for you. We tried to come up with ways of adding complexity because we were afraid it would be too easy, that it wouldn’t push the limits of what you can do.

All in all, it was really inspiring to interact with students who were so interested in science that they found it fun. One of the highlights of being here in Europe for me was actually being part of S3.

The feeling is mutual, Sindhuja and you were impeccable project leaders. Would you say that the Summer School is a useful and not just a fun experience?

The heart of the Summer School seems to lie in working with what you’ve got. You may not have the resources to answer a question, but you definitely have the resources to ask the question. That itself is such a big part of discovery, I think maybe even the most important part. So many breakthroughs have come about from people hitting the limits of what their resources could do and having to come up with new ways of doing things. The Summer School does this at a more fundamental level, but it still pushes the same way of thinking – you can ask questions, you can do an experiment, even at home. I think that was the main goal of S3, to explain that there is no question out of reach. You can ask really fundamental questions about nature and life and anything, and make a little bit of a headway into it with the limited tools you have on hand. Also, the simplest questions are often the most profound. That is, again, a very valuable lesson. And that lesson is not something only the participants learn, but something that I learned too. Because the experiments worked so well and we were enjoying it just as much learning about them with you all, it was expanding our minds as well.

If you had to recount what the S3 experience was like to someone in one story, which one would you tell?

It depends on who I was talking to.

Let’s say it was a fellow scientist. I would tell them about when we were trying to make gels. Every time we were preparing the SDS-PAGE, which is something all biochemists know very well, the gel would solidify and then liquify. We could never get it to stay solidified. We changed everything we could think of, but nothing fixed it. We finally figured out that the water we were using was distilled but not deionized and the ions were messing with the polymerization. Since we had to run proteins and we knew agarose gels would work if the proteins were big enough, we simply ran them in agarose and put them under UV light. We saw everything very nicely because the proteins were fluorescent. This is one of my favorite problem-solving anecdotes from the Summer School and the one I would definitely tell a colleague. Deionized water is such a basic commodity in a lab that you take it for granted.

If it was a non-scientist friend, for example, I would tell them about the time we were visited by the Croatian Minister for Labor. It was in the first few days of the project. We told him we were exploring why leaves turned yellow and showed him some of our preliminary results and such. While we were talking, he took myself and Sindhuja aside and asked why it was that leaves changed color. We said we couldn’t tell him just yet, but he looked so genuinely intrigued by it. I loved that he was so curious about it. We finally explained (spoilers) that the other colors are already in the leaf, the chlorophyll degrades and the other colours get left behind in autumn. He was so fascinated by it. I think that is a good story to explain what the Summer School is about – you can be a minister and still be curious about seemingly simple questions.

That was a wonderful selection. One last thing: is there a piece of personal wisdom or advice that you would like to share?

This is one thing that I wish I could tell myself when I was younger, which we touched upon earlier. It’s really a two-part idea; for one, don’t be too hard on yourself. There are multiple ways to become successful in the world we live in or in the world of the future, there is no one path. So, don’t fret if you don’t hit certain targets that your peers have hit or that you have set for yourself. This is something I am still learning and it’s a wasteful habit that I wish I had nipped in the bud. A little bit of an extension of that is the other thing, which is to be free to explore. If you feel like taking your time to find your true interest, do it. Even if you don’t find the interest that drives you, it’s okay, just keep exploring. It’s okay to step out of the race. That is another thing I don’t do. That’s why I’m telling you these things – because I’m not there yet either.

Thank you once again for taking the time to tell us your story, Srinath! It will no doubt inspire and excite many of our audience, young and old.

Have any questions for Srinath? Leave a comment and ask away, I am sure he will be more than glad to discuss anything you have in mind.