Decoding the Dogma: Dr. Gene-Wei Li on quantitative analysis of the genome and being named an HHMI Investigator
The Li lab focuses on measuring how transcribed and translated different genes are.
Dr. Gene-Wei Li is an associate professor of biology at MIT who researches how quantitative information is encoded in the genome. After his undergraduate and graduate studies in physics, he became interested in a multitude of unanswered questions about biology. He completed his postdoctoral training at the University of California, San Francisco before joining MIT’s faculty in 2015. In July, he, along with three other Institute faculty, was appointed as a Howard Hughes Medical Institute (HHMI) investigator. Investigators receive $11 million in funding over a seven-year term.
Here, he shares his journey and hopes for the future and what he values in research and at MIT.
TT: Could you tell us about your interests and research in biology—past, present, and future?
There's so many unanswered questions that are fundamental to biology. Coming from a more quantitative background, there were a lot of approaches and thinking that I could offer that differ somewhat from traditional biology training. There was a transition into a new approach of looking at biological systems, which is, instead of looking at qualitative descriptions of what molecules do, there's a lot more quantitative thinking involved.
A human genome has 20,000 genes, and they are roughly equally represented in our genome—we have two copies of each gene. But when they're made into proteins, they're hugely different in their abundances. It's the differences in abundance that really drive all the phenotypes. So deep down, it’s those quantities that matter. When I was in grad school, I was amazed by how little we know about these concentrations of different proteins in the cell, so I've always been interested in that and trying to get better at measuring those. I'm hopeful that in 10 years, at least in bacterial systems, which are relatively simple, we will be able to go from DNA sequence to all the steps in the central dogma: knowing how much RNA is made, how stable the RNA is, and how much protein is going to be produced. There are a lot of really practical implications, but I think at the basic biology level, being able to do that tells us we really understand the mechanism of the central dogma.
HHMI certainly allows us to think bigger and to not be constrained by funding sources. This funding is really, really critical for us. Oftentimes science doesn't go as planned, and you're in this new frontier, so it's very likely that people are going to find new things. I've been really lucky to work with some really talented graduate students at MIT. They really take science to a different level and in different directions. When those new directions arise, HHMI funding allows us to run with them.
TT: What are the biggest takeaways from your time at MIT so far?
I started at MIT in 2015, almost 10 years ago. How supportive the environment is is really critical. For example, this HHMI application process: it's not just me. My department was very supportive and gave me feedback. My students and postdocs all read my application and their work contributed tremendously. When I talk to colleagues at other places, I feel like our department at MIT is pretty unique. It's really driven by science and driven by creating an environment that’s supportive and not super competitive. The world is competitive, but not within the department. It makes everything so much more fun and exciting and productive. So I really enjoy this process, being at MIT.
MIT is really cool in the sense that every junior faculty has two senior faculty mentors, and I really rely on them a lot. Mine are Stephen Bell and David Bartel. I would always run to them when I have questions. There are other unofficial mentors whom I rely on, like Alan Grossman, Bob Sauer, and Angelika Amon, who unfortunately passed away. She was very, very helpful. So there are many people and I probably forgot some of them, but it's really a privilege to have all those people who can share their knowledge and give me feedback.
We have been really lucky at MIT to have the freedom to pursue the things that we love. For my lab, there is internal funding and support from the department in the School of Science, so we have been able to leverage that. Especially as a junior faculty, there's a lot of cool things you can do. Going into a more senior level, it becomes harder and harder to get funding for new ideas and new directions.
TT: Do you have any advice for MIT students looking to pursue biology?
Curiosity is the most important thing. There are different types of research we do, and the one we value the most is curiosity-driven research. We're not bound by certain deliverables or goals that are set by outside sources—we're internally driven. So I encourage everyone to be really curious about the things they are working on, and be able to make a transition such that they are the world expert in the areas they work on. It's going to be hard. A lot of students, myself included, are still learning a lot of biology. It's okay to acknowledge that I don't know stuff—we're all here to learn. I still remember, at the end of my freshman year doing research, I had no clue what people were talking about. But you start to get immersed in the environment, knowing that people are excited about things they're working on. And then slowly, they're going to all come together and you start to see threads. You start to see principles of how people work together and how people ask questions. So don't be afraid and be curious.
I love to be my students’ strongest advocate, and I take students in with the thinking that they will be successful. There are different angles to look at success: some people want to be successful in this career, some people want to be successful in a different career 10 years down the road. We ought to provide them with the path and support to prepare them for both. In the meantime, we ought to build a community that is really excited about science and excited about things that we're working on. That all makes it really nice so that people can see why they're doing this, and invest in their career development as well.