Meet our Speakers: Dr. Yuh Min Chook
The Yale Cell Biology Department was honored to host Dr. Yuh Min Chook as its November seminar speaker. Dr. Chook is a Professor, Eugene McDermott Scholar in Biomedical Research, and holds the Alfred and Mabel Gilman Chair in Molecular Pharmacology at the University of Texas Southwestern Medical Center. A leader in the field of nuclear-cytoplasmic transport, her research encompasses defining nuclear export sequence (NES) and nuclear localization sequence (NLS) motifs as well as structural elements governing transport between the nucleus and cytoplasm, inhibiting nuclear transport, and investigating how karyopherins function as chaperones. In this interview, Dr. Chook shared the experiences that sparked her passion for research, the questions that currently excite her lab, her love for cooking, and her advice for graduate students at the beginning of their careers.
What experiences led you to pursue a research career?
I started doing research the summer after my junior year as an undergraduate and I loved it. I was taught different techniques by a postdoc in the lab, and afterwards I had the freedom to do them myself, make my own mistakes, and improve in my own time. The lab setting gave me the flexibility to take as long as I wanted to improve -- I didn't have to learn how to do the techniques correctly immediately. That was so different from lab classes with a partner and a set time frame. When I had a lab partner with more experience, they would be impatient with how slow I was, and I wasn’t learning because they were taking over to be more efficient. I needed more practice with my hands initially, and research allowed me the time to do my best. I could work as many hours as I needed, and learning things at my own pace gave me a lot of peace.
Additionally, I found satisfaction in the hands-on, everyday work of doing the experiments and getting a conclusive result, even if it was a very simple one. The sense of discovery, and knowing that you were the first person to know something because you got the experiment to work, was very satisfying.
I also had a professor who loved protein biochemistry and structure, which was a new field at the time in the 1980s. He passed that enthusiasm on to me which, combined with my love of biology and physical chemistry, led me to pursue structural biology in graduate school.
What questions are you and your lab currently interested in?
We are interested in the idea of NLS and NES motifs and how prevalent they are. They might not be as prevalent as we think: maybe not all karyopherins need to have an NLS or NES as defined by a linear sequence motif. More instances of domains are being recognized instead, and while linear motifs are easy to find on different proteins, domains are harder, and they raise more questions. For example, there aren't many shapes of domains, so the specificity for nuclear targeting must come from differences in surface chemistry. So, how can you figure out what’s going to be the cargo of a specific karyopherin by just knowing a domain? How general is a domain for targeting? We’re also interested in how the structure of karyopherins affects targeting since these proteins are flexible and can adopt various conformations that bind different cargo. The problem of targeting for nuclear transport is much more complicated than we previously thought.
What do you find most exciting about the field of nuclear-cytoplasmic transport?
Nuclear-cytoplasmic transport is such a fundamental process. What goes in and out of the nucleus controls many things in the cell, but there is still so much that we don’t know about it. We don’t know the traffic patterns in and out of the nucleus or if every nuclear pore is the same – pores at different locations may have different compositions or even different functions. There are also increasing instances of minor aberrations in nuclear-cytoplasmic transport causing disease. The field needs to gather fundamental knowledge about the process, because without it we may not be able to explain certain human diseases.
What’s an obstacle you’ve faced in your career?
Funding is always an obstacle, and it’s a big obstacle right now. Grant amounts are not being increased as postdoc salaries, student stipends, and tuition go up, and it becomes zero-sum game. It’s important to pay trainees well so they can live properly and do their work to learn to become scientists. But at the same time, it means the lab cannot thrive, because what used to be a 3-person grant is only funding 1.5 persons. So what kind of environment does that provide for trainees? It also means there will be fewer positions in the lab going forward. That is a big obstacle.
A challenge in research is trying to figure out the next exciting problem to pursue as the lab progresses and how we want to approach it. My trainees have often made that decision for me because they are wise and could decide what was most exciting for them. I have been very lucky that I’ve always had brave trainees who have taken on challenging paths. Even if I thought a path was unwise or we were late to a problem, we succeeded because of my trainees.
Another challenge is hitting roadblocks with a project -- when you come to the realization that you can’t solve the problem at hand to the extent that you want. It’s important not to give up, but it’s also important to know when you can stop, publish, and start a new collection of work. Not everything needs to be solved in one paper.
What is a hobby you enjoy outside of the lab?
I love to cook. And I came to the hobby because of lab work. I love being at the bench, but a few years after I started running my lab, I had no time left for bench work. When that happened, I realized I still had a great need to work with my hands, and the way to satisfy that was through cooking at home. If you ask my colleagues, they’ll tell you that I also love reading about food. I follow news on food and read restaurant reviews and all sorts of culinary literature.
- 1. What advice do you have for trainees who are early in their careers?
I would say to remember why you came to graduate school: to learn how to do research and generate new knowledge in biomedical science in a rigorous way. Learning how to do that is the most precious thing that you will get out of graduate school because so many things tie into it: organization, an understanding of the scientific process, persistence, troubleshooting, and solving problems. If you do that well, you are set with any career. Along the way that goal can be clouded over by the need to explore different paths and careers. But don’t forget you still need to do this fundamental thing of learning to do science, because that will give you many of the skills you will need for any science-related career. Whether you stay a scientist or not, you need to have the experience of doing science to the best of your ability.