BioGenesis Podcast: Cesar Dominguez of the Schwartz Lab on how cells withstand and transmit mechanical force

From MIT Biology and Whitehead Institute: BioGenesis is the podcast where we get to know a biologist, where they came from, and where they’re going next. In each episode, co-hosts Raleigh McElvery, Communications Coordinator at MIT Biology, and Conor Gearin, Digital and Social Media Specialist at Whitehead Institute, introduce a different student from the Department of Biology, and — as the title of the podcast suggests — explore the guest’s origin story.

Season 3 features stories of breaking the mold. In our third and final episode, we’ll meet Cesar Dominguez. His family emigrated from Mexico to the U.S. at a young age. Growing up in a relatively homogenous community led him to seek out more diverse perspectives as he honed his research skills in structural biology. He now studies how cells can withstand and transmit mechanical force.

Subscribe to BioGenesis on iTunes, Spotify, Google Play, or SoundCloud to keep up with season 3! 

Edited Transcript

Cesar Dominguez: My concept of a scientist as a child was probably similar to my unquestioned concepts of a lot of other professions. Like, when I thought of a doctor or scientist, I probably thought of some white male in a lab coat. And I didn't really question that because that was the world that I lived in in New Hampshire. I was very aware, however, that my family was different.

Raleigh McElvery: Welcome to the final episode in this season of BioGenesis — the podcast where we get to know a biologist, where they came from, and where they’re going next. I’m Raleigh McElvery from the MIT Department of Biology —

Conor Gearin: And I’m Conor Gearin from Whitehead Institute. Today, our final story about grad students “Breaking the Mold” features Cesar Dominguez.

McElvery: You’ll hear about what it was like for him to emigrate from Mexico to the U.S. at a young age. 

Gearin: And, how growing up in a relatively homogenous community led him to seek out more diverse perspectives as he honed his research skills in structural biology.

Cesar Dominguez: Hello, my name is Cesar Dominguez, and I'm a second-year graduate student in the Biology Department at MIT and I'm in Thomas Schwartz's lab. My family and I are from Mexico in a very rural area of Zacatecas. Zacatecas is a state. It's not very touristy at all, especially the region where I'm from. It's mainly just valleys of agriculture, beans, oats, barley. A lot of peaches. It's probably a thousand people max. And everyone is related. Everyone knows each other. It's the type of place where you walk down the street and people are just sitting out on their porches, and you're expected to say hi because everyone knows each other — otherwise there will ensue some rumors or something.

The first characteristic that people note of my family is that it's pretty big. I am one of seven children. I'm number six in the line. We're a pretty loud bunch. I'm described as the quietest one, which is OK with me.

McElvery: When Cesar was just three years old, his family moved to Colorado, and then ultimately settled in New Hampshire so his father could work in a textile factory there.

Cesar Dominguez: When we came to the U.S. originally, initially, we only intended to stay for three years because my father — yeah, my parents were very rooted where we're from. Our whole family's there, all of our memories and way of life. But he wanted to give us the ability to speak English and papers so that we could have more flexibility and more opportunities. We came up on a bus with two suitcases, that’s the story.

There was no thought about science at all — didn't ever cross my mind when I first moved to New Hampshire. I really just drew a lot, I wanted to be an artist. I was fortunate to be in the lineup of my six siblings where, when I was four, I was around my older siblings who were either learning to do stuff in English, so I would go along with them. And then while they were learning their multiplication tables and whatnot, I would just go along with them. And I learned everything like a little ahead of time. 

My eldest sister went to college and she brought home some biology textbook from her intro bio class. And I remember the figures in the biology textbook were very, I don't know, there was a lot of color, a lot of beautiful diagrams. So I think that was my first official exposure to institutionalized science education or science something or other. 

Gearin: School became a second home of sorts, and Cesar immersed himself in homework and extracurriculars.

Cesar Dominguez: And it worked to help me become a very good student and at least find a home there. And that's not the case for a lot of immigrants. Children unconsciously internalize a form of shame with their native tongue, when they're not surrounded by peers who speak that same native tongue, and culture and foods and customs. Especially when we're just trying to fit in and figure things out. I'm not saying that's OK, I'm just saying that's how it was. 

By tenth grade I knew I was very interested in science, in biology specifically, because those were my best teachers. I have very fond memories of all of them. And when I learned about photosynthesis, that was astounding to me that we could know all of these intricate things about something called cells. And I ended up enrolling in some biotechnology course.

McElvery: Cesar’s biotechnology teacher had completed her postdoc at MIT’s Koch Institute, and even took her students to visit campus.

Cesar Dominguez: The fact that she was a woman was great and a good role model to really expand the unquestioned picture I had of a lot of professions. There was no doubt in my mind that I was going to go to college because of all that. It just felt very natural. 

Just like everything else that had gone on in my education since elementary school, I did it on my own. Not to be braggy or anything, but it was just a case that my parents... institutionalized education was not a place that they felt very comfortable. And especially in a language that they weren't familiar with. 

Gearin: As he was beginning the college application process, Cesar received some materials in the mail from a non-profit called Questbridge, which connects exceptional students from low-income backgrounds with higher ed institutions.

Cesar Dominguez: Once I learned about that, I was set for sure on trying to get into one of those schools that was on their list. I ended up giving Williams a shot. I visited on their accepted students’ day. My host, he was also a Mexican-American from California, also studying biology and chemistry. And we got along very well. And for the first time in my life, seeing someone else with, I don't know, maybe some familiarity, interested intellectually in some of the things I was interested in… And he was encouraging me to go there. And so were all of these professors. I'm like, maybe, yeah, I'll give this place a shot. 

McElvery: Williams also had a summer science program, designed for incoming first-years who were first-generation college students or from historically under-represented groups in science.  

Cesar Dominguez: I was with a group of 20-something students, all from various backgrounds that I had never actually been in a classroom with in New Hampshire. I was used to being the only Mexican-American student in my classes growing up. And I learned not to bring that up. That's what I was accustomed to. And so when I got to college and saw all of my peers were not like that, it really completely flipped the world of the classroom for me, to be honest. 

Gearin: A biology major and French minor, Cesar was following the premed track, and found opportunities for life science research wherever he could.

Cesar Dominguez: Yeah, yeah, I did do research, fortunately, because that's really what guided me to where I am.

McElvery: He worked in one lab at Williams for four years, studying mosses and investigating the genes they use to metabolize lipids.

Cesar Dominguez: I didn't really understand what I was doing, but I put the puzzle pieces eventually together, obviously.
 
Gearin: He also spent a summer at Brown University, investigating the role of insulin metabolism in Alzheimer’s disease.

Cesar Dominguez: It was very satisfying, again, when I put the whole picture together and contextualized what I was doing in the laboratory.

McElvery: Then there was his summer abroad in France, when he took on a side job in a hospital bacteriology lab. 

Cesar Dominguez: And then I realized after the experience that it didn't attract me as much as academic research, where things are a little more uncertain and more anxious and frightening because things are so uncertain. But that was also exciting and more satisfying for me. 

Gearin: Working at a lab in at the University of Massachusetts Medical School affirmed his suspicions that he preferred the lab bench to the bedside. So, his boss encouraged him to apply to graduate schools.

Cesar Dominguez: I ended up deciding on attending MIT specifically because I was prioritizing staying close to my family.

McElvery: He began in the fall of 2019, not knowing that his first year of graduate school would soon be interrupted by the COVID-19 pandemic.  

Gearin: After a series of remote rotations that mainly included reviewing published literature and analyzing previously collected data, he settled on the Schwartz lab.

Cesar Dominguez: We use structural biology as a technique to understand very fundamental cellular processes. If I were to describe a structural biology, I think of how microscopes in general allow us to look at something that our eyes can't see. And microscopes allow us to zoom in to see bacteria and cells, but there's a limitation to light. We can't use light to zoom in to see molecular machines that are proteins and related macromolecules. So there are alternatives, alternatives to light that we can use, and that’s X-rays or electrons. And these are more involved. And they're focused on trying to see, even at a much smaller atomic scale, see the three-dimensional positions of all of these atoms that make proteins, and allow us to see and understand what is going on with this macromolecule and how it does what it does. 

McElvery: The Schwartz lab leverages structural biology techniques to probe one cellular organelle in particular: the nucleus, where most of our DNA is stored.

Cesar Dominguez: The nucleus essentially safeguards our genome in eukaryotes.

Gearin: For protection, it’s surrounded by two lipid bilayer membranes that form the nuclear envelope, which only allows certain materials in and out through tiny pores.

Cesar Dominguez: There's always traffic, material trafficking, in and out of the nucleus. And there's also, to my surprise — because I didn't know this before I joined the lab — there's also mechanical communication, where there are mechanical forces that apparently are transferred across the nuclear envelope and allow a lot of processes to occur that are essential for eukaryotic health. 

McElvery: Forces can be transmitted between the nucleus and the rest of the cell, in order to position and anchor the nucleus during important processes like development. Cesar studies one protein complex in particular that acts like a bridge, transferring force between the nuclear envelope and the network of structural filaments outside the nucleus that give structure to the cell.

Cesar Dominguez: Yes, my focus in the lab is on the LINC complex, which is the main protein or molecular tether that connects the skeleton within the nucleus with the skeleton that's in the cytoplasm. 

Gearin: If something goes wrong with the LINC complex, muscle diseases like dystrophy or ataxia can ensue. 

McElvery: As a second-year PhD student, Cesar is still narrowing and refining the plethora of possible projects.

Cesar Dominguez: Right now, I'm still in the process of developing actual directions. But definitely one aspect that I'm interested in is structurally determining or investigating these complexes in lower organisms or other organisms that aren't humans — because we mainly know only about the human LINC complexes. And so whatever we learn, it'll help us design maybe more careful experiments or more impactful experiments in these model organisms that will later inform our human biology. And then something else that would be of interest would be directly measuring the mechanical forces that these LINC complexes can withstand. 

Gearin: Since research has started to ramp up again post-COVID shutdown, Cesar has spent his time isolating LINC complex proteins to further analyze them.

Cesar Dominguez: I'm in the process of figuring out, getting a sense of how these proteins behave in solution to keep the complexes together. That just requires testing — a lot of empirical trial and error, which I really like. I think the more difficult part for me was actually balancing teaching with starting in a new lab. That was very challenging.
McElvery: Like all MIT Biology graduate students, Cesar served as a teaching assistant, or TA, during one semester his second year – an assignment he finished virtually due to COVID-19 restrictions.

Cesar Dominguez: I really do enjoy the process of teaching. It's something that I did throughout undergrad. And if I look farther back in time, I've taught my younger sister and younger cousins about how to read and do basic math. It's always refreshing to reconnect with these with concepts that are taught in intro bio classes, because every time I see them, or when I revisit them, I'm coming from a different time where I'm thinking about some other aspect of biology. And so when I reconnect to it, I have a deeper sense of its meaning. And also, a lot of times it helps me look back on my research from a different angle sometimes. 

Gearin: He’s also a graduate residence advisor in an undergrad dorm — although that, too, has recently gone virtual. 

Cesar Dominguez: The house has been empty, and that's not what I expected going in to this resident advisor position. But I have been able to get to meet with students over Zoom and just connect with them virtually. 

McElvery: Through his teaching and resident advising, Cesar is hoping to create an open community that’s eager to discuss issues of diversity in science. 

Cesar Dominguez: I think it starts out from having teachers that are encouraging and welcoming to the practice of learning — the ability and interest to learn about our surroundings. Typically because science tries to be objective, I think we run into this problem of not always going into the background stories of all the scientists. And one of the ways I do that specifically is just being a little more open about certain experiences that I know aren't always talked about. Like, getting Christmas gifts from the Salvation Army every winter growing up. That was my Christmas. And I don't know, that just came up because we were talking about gifts the other day in lab and I just brought that up. And it just brings an awareness that people don't really talk about — different backgrounds — and those exist. I just think storytelling is powerful.

McElvery: That’s a wrap on Season 3. We hope to bring you more stories soon, so stay tuned.

Gearin: Subscribe to the podcast on Soundcloud and iTunes or find us on our websites at MIT Biology and Whitehead Institute.

McElvery: Thanks for listening.
Credits

Produced by Raleigh McElvery and Conor Gearin.
Music for this episode came from the Free Music Archive and Blue Dot Sessions at www.sessions.blue. In order of appearance:

“Something Elated” — Broke for Free
“Kilkerrin” — Blue Dot Sessions
“Valley VX” — Blue Dot Sessions
“Brad PKL” — Blue Dot Sessions
“Jog to the Water” — Blue Dot Sessions
“Cach PKL” — Blue Dot Sessions
“Chafftop” — Blue Dot Sessions
“Pacific Time” — Blue Dot Sessions
“Dimming Circuit” — Blue Dot Sessions