Dr. John Calarco

Dr. John Calarco

Can you describe your current position at Harvard?

I’m a Bauer Fellow, which is a position in between a proper faculty position and a post-doc. It’s a type of transition position where I have complete creative and experimental independence but with a great mentoring support system: I have PI status, I can write grants and I have a lab with two post-doctoral fellows. I’m also given a research budget and funding to run that lab. I’m still working at the bench full-time, which raises some interesting challenges in terms of managing a group and doing full-time research. The environment here is really great and supportive. They minimize the amount of teaching we have to do so that we can manage a lab and do bench work ourselves. For all intents and purposes, I’m an independent researcher but it’s not a tenure-track position. I have a five-year term at this position and then I hope to find a faculty position after that.


What is the focus of your research?

My research right now stems from work that I conducted as a PhD student. It is a spin-off of a joint project I started while in Mei Zhen and Ben Blencowe’s labs using C. elegans as a model system to study alternative splicing regulation in the nervous system. The lab has two main areas of interest: understanding how splicing decisions are regulated at the level of individual neurons in the animal and which isoforms are important for proper development and function of the nervous system. The work involves a combination of cell biology, genetics, molecular biology, and genomics.


What is the most challenging aspect of your job?

Managing people is the hardest part of the job. I know it’s a bit clichéd, but it’s something that nobody prepares you for. The learning curve was probably steeper for me because I was coming straight out of a PhD. There’s also this dynamic where your post-docs are roughly the same age as you and yet you have more experience than them because they’re coming from a different field. So it’s striking a balance between being a colleague and also being an advisor. It’s one of the main challenges I face in my current position. The other challenge is splitting my time between managing and doing bench science myself.


When did you realize that you wanted to become a scientist?

I think it was around high school. I was starting to get really excited about the biology that I was learning and picked up a book at my local library about the genetic code and the central dogma of molecular biology. It was just a simple type of introductory manual but I thought that what was described was such an amazing concept. Particularly how codons had evolved and played a role in specifying amino acids and ultimately, creating a peptide chain - it was really exciting and inspiring to me at the time. It led to me deciding that I wanted to get into a molecular biology and biochemistry stream in university. So that was really the start of me being very interested in biology.


Why did you decide to pursue your graduate studies in the Department of Molecular Genetics?

My decision to join Molecular Genetics evolved fluidly from undergrad because I had started working in Ben Blencowe’s lab as an undergraduate student in my second year. I started chatting with Ben and became more and more interested in the research that he was doing. Ben was nice enough to offer me a summer position at the end of second year. One thing led to another, and I started working on projects and stayed on through third and fourth year. In fourth year, I had a thesis project and one of the projects from my thesis work was getting to a point where it was really exciting. I knew I wanted to stay as a graduate student and I thought there would be no better place since Ben was doing some really fantastic work. At the same time, I was interested in model organism genetics so Mei’s research program was also very attractive. I ended up doing rotations in both labs and doing my PhD under the co-supervision of Ben and Mei. Toronto was also just a great city and I felt it was a world-class place to do a PhD. I ultimately decided that I didn’t want to go anywhere else.


How did your experience in Molecular Genetics influence your career trajectory?

My experience as a PhD student was where I fell in love with doing experimental research. It was a great opportunity to explore research first-hand, get a feel for how science was done, and learn about genomics and other techniques, and how to dissect problems. Once I started doing all the technical work, I really loved the idea of doing academic research for the rest of my life. That was what really influenced me to continue on. Some great interactions with both of my PhD advisors and my thesis committee helped get me to my current position at Harvard. It was actually a conversation with Peter Roy, who was on my thesis committee but also a really great faculty advisor. I was working mainly in the CCBR and whenever I needed to do some C. elegans work and couldn’t get to Mount Sinai, Peter was nice enough to let me use some of his equipment. At one point, I was in the microscope room, Peter and I were chatting and he asked what I was planning on doing next. I told him I was thinking about post-docs and some of these independent fellow-type positions. He mentioned that he knew about the Bauer Fellows program and connected me with a colleague of his who had been a previous Bauer fellow. That connection helped me to get my CV forwarded to the right people, so I have him to thank for pointing me in the right direction.


Can you share some of your favourite memories from graduate school?

The retreats were an enormous amount of fun. That was a great place to meet fellow graduate students and see faculty outside a lab setting. The collegiality of the community and the people you interact with in the department are definitely great. Some of my best friends are people that I worked with in the lab. The faculty were absolutely fantastic and great to interact with. I would say it was mostly the people that provided the most positive experiences.


You won the Barbara Vivash award for the most outstanding PhD thesis and were also named by Forbes magazine in their “30 under 30: Science” a few years ago. How have recognitions like that had an impact on your career?

They’re certainly great acknowledgements and I have been really grateful and fortunate to receive them. In the immediate term, they have certainly helped with getting fellowships and other funding. These acknowledgements also present opportunities to attend many events and meetings, so in that way, they allow you to gain recognition and meet people that you wouldn’t otherwise meet.


What scientific discovery are you most proud of?

The work that I’ve been most proud of shed light on and deepened our appreciation for co- and post-transcriptional gene regulation in the establishment of tissue and cell-type diversity. In particular, my work on RNA processing and how it adds an additional layer to diversify an animal’s transcriptional repertoire, the ability to differentiate, and the potential for evolution. These are concepts that were laid down in the thesis work that I did and are guiding me in the new research that I’m conducting here at Harvard.


What was the most important thing you learned in graduate school?

In the end, you need to have fun. You need to make sure that what you’re doing is fun and that you enjoy it. A lot of the work we do is often thankless and there’s a lot of work involved and a lot of failure to deal with. You need to have a good balance and keep your head focused on the bigger picture. There may be an assay or something that’s not working in the short term but in the long term, you have this goal that you want to work towards. You have to have the desire and the motivation to do it. I think that if you’re not having fun, it can make the journey that much tougher.


What was the best advice you received when you were preparing to graduate?

Both of my advisors were great at giving me the confidence to even consider applying for my current position. When I drew close to finishing my thesis and started to think about post-doc options, I knew that I definitely wanted to be in academic research. At the time, I was just considering following the traditional path and doing a post-doc. Both Ben and Mei really encouraged me to apply for one of these fellow positions because they were confident that I was already capable of managing a lab and doing independent research, and that I would be up for the challenge of a position like this. I’m really thankful that they did because it pushed me in that direction. After hearing their encouragement, I started really believing that I could do this and I don’t regret it. It’s been a fantastic opportunity and a very rewarding experience.


What advice would you give to students who are thinking of pursuing a career in academia?

To current students, again I would make sure that you enjoy what you’re doing. Work really hard but definitely make sure you don’t forget to have fun and that you take full advantage of the resources available to you as a student. That includes your advisors, committee members and also the core faculty of the department that you can get to know. They’re not just there to question you at committee meetings and stress you out during presentations. They are there to interact with you and they really do love to teach so it’s a great experience when you can interact with them outside of their typical roles as thesis advisors or committee members.