Meet a Whitehead Postdoc: Jay Thangappan

Jayaraman (Jay) Thangappan is a postdoc in Whitehead Institute Fellow Silvia (Silvi) Rouskin’s lab investigating RNA structure. We sat down with Thangappan to learn more about him and his experiences in and out of the lab.

What are you investigating?

Our lab specializes in RNA structural determination, and how that can regulate gene expression. For a long time, DNA and protein were the major factors considered in our understanding of biology, but now there are a lot of things happening with RNA. One of the biggest things people don't know about RNA is its structure — its two and three-dimensional shape — and how that relates to the function of the proteins translated from RNA. After a gene is transcribed into RNA, that RNA is spliced, removing parts of the sequence and leaving the exons, which are the parts that gets translated into protein. Depending on how the RNA is structured at specific junctions of the splicing, certain parts of exons can be missed, or other parts can be included. This affects what proteins are formed and how they function.

The lab’s main project is looking at the structure-function relationship in HIV RNA, which has a lot of structured and unstructured regions. The project I'm working on involves tau protein, which is involved in neuronal function. I'm specifically working on how RNA structure influences splicing for specific proteins like tau. I'm also computationally looking across the genome at other genes and other proteins where RNA structure influences splicing and, in turn, gene expression. I’m really interested in this relationship between structure and function.

What are the translations aspects of your research?

The protein I'm investigating, tau, is involved in neuronal function, and when defective it can contribute to neurodegenerative diseases, like Alzheimer's, Parkinson's, and dementia. In these diseases, there can be a mutation at the splice sites of the tau RNA; we believe this mutation affects the structure of the RNA at these crucial junctions, which in turn impacts the protein function and so can result in these neurodegenerative diseases. By identifying which regions of RNA structure are involved in the proper function of the protein (such as splicing junctions), we can detect when these RNA regions are not structured correctly, and predict disease risk or progression. This could also help us identify and develop suitable RNA-based therapeutics.

How did you end up at Whitehead Institute?

I'm originally from the southern part of India and I did my PhD in South Korea. As I was wrapping up my PhD in 2017, I started looking for places where I could do my postdoc that would align with my research interests and allow me to learn something new. My PhD work was focused on protein engineering, but I had become more interested in RNA, and specifically in the relationship between structure and function. I listened to a lot of talks and read a lot, and I felt Silvi was someone who is working on something new and interesting in RNA structure: how RNA conformations can make huge differences in protein expression. I wrote to Silvi, she interviewed me a couple of times and right away I felt like this would be the perfect place for me. Silvi is actually the one who came to the airport to pick me up when I first arrived in Boston. I didn’t know anyone here; it was my first trip to the states.

Silvi Rouskin is a Whitehead Institute Fellow (a position that gives recent PhD graduates a role running a lab instead of a traditional postdoc position). What is it like being in a Fellow’s lab?

Our lab is a very small group. I'm the first postdoc in the lab, and Silvi was never a postdoc herself, so we all had to figure out what my role was. When I joined the lab, I was like a student in that I had no idea how the lab works, because I was switching fields from protein folding to RNA and because I’m a computational guy while the lab is experimental. They still treat me like a newbie. One big difference being in this lab is that I don’t get to interact much with other postdocs, because I’m the only one in the lab, and the institute-wide postdoc meetings happen at the same time as the Fellows meeting, so I can’t attend. But I have lots of freedom to learn and interact, and everyone at Whitehead Institute is very supportive. When you need something, you can always go and talk to someone and they will offer you a solution, no matter what stage of their career they are in. Also, Silvi is a great mentor, both with the research and for talking about future plans and work-life balance. It's a great advantage for me to work with her, because she's also young and she knows the transformation process from student to independent researcher very well.

What is it like being a computational researcher?

For computational people, I would say either you can be a hardcore programmer or you can be a data analyst, and I am the latter. I collect a lot of data, and reexamine things that people have already looked at. I don't have anything to set up at the experimental level. My project involves experimental steps, but people in the lab help me. My day to day is all about the computational analysis, so I start with a dataset, run an analysis, and wait to get results. My PhD advisor used to say all you need to be a computational researcher is good computational power. There are fewer time and money constraints than experimental research. You have the flexibility to work from home or wherever you like. Sometimes I come into the lab on the weekends if there is something to be run, because everything I do requires a lot of computational power, and when I am running multiple things it’s nice to use the computational resources here. But I like being a computational guy. You have a lot of time to explore whatever you want, to try different things. If one approach doesn't work out, then you can try something else. Experiments require more planning up front. Of course, I still have to plan, but I have fewer constraints and more flexibility. I can learn things quickly, and I enjoy that.

What are your hobbies outside of work?

I bike a lot. I like to cook, watch movies, and read things other than scientific papers. I really like to run. Recently I started running with [Whitehead Institute Member] Sebastian Lourido's lab. We run at the esplanade, along the Charles River near MIT. I enjoy running with them, but even before joining that group I used to run myself, although not as much. Now I run a 5K every day. 

Where do you like to travel?

Everywhere. Traveling is one of my favorite things to do, although actually when I was younger I never left my hometown. I get motion sick very easily, so I always used to try to bike places because I would get sick on the train or the bus. That's why I did all my schooling — undergrad, master's — in my hometown. My parents and friends, everyone thought I wasn't fit to travel. Not that they didn't want me to go places, but they were worried no one would be there to take care of me if I got sick. Then during my master's, I became friends with people from all over India and I started traveling to their homes. India is big, not as huge as the U.S., but it has 29 states and I think I've been to 26. When I started traveling, I still would feel sick but I learned how to manage. I still have that difficulty but now I see it as an opportunity to go somewhere and learn something about myself. I feel really good once I get to the destination, so maybe part of the journey isn’t so fun, but I close my eyes, put on my headset, try to sleep, and at the end when you get there it's worth it. It's like reaching the top of the mountain after a strenuous hike. Since then I’ve been to lots of places. I really like going to places with different cultures, where I don’t speak the language, where I get to challenge myself, and learn and appreciate new things.

What’s a favorite recent trip of yours?

Last month we attended a conference in Berlin. It was four days, and I couldn't do much in the city because of the conference, but I got to see the most famous places and then I travelled a little bit. I got one day to go out of Berlin, to Potsdam, which was very nice. It's a very beautiful place with palaces and gardens. After that, I went to Prague and met up with one of my classmates who is doing her PhD there. It’s an ancient city, very beautiful, very lively, and full of people. I spent a day in the city and then a day outside of it, so I got the city feel and the country feel. Then we went to Amsterdam, and a nearby countryside village (Zaanse Schans) with a lot of windmills. I took a lot of pictures. The whole trip was fun and wonderful.

Where do you see yourself in ten years?

I'm not sure where I'm going to be, but I would love to be an independent researcher either in academics or in industry. I would like to have my own lab and be able to pursue the research questions I’m most interested in.