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Biophysicist in Profile

Sarah L. Keller

Sarah L. Keller

November 2024 // 104

When she was young, Sarah L. Keller remembers worrying about what she would be when she grew up. “I had no idea how to choose. Maybe that’s one reason I feel at home in biophysics, where I think about interdisciplinary topics!”

Keller feels that “every life decision has both a push and a pull. My family moved across the US in my first year of high school. At my old school, my most engaging mentors taught writing. In my new school, my science teachers were much stronger, especially my physics teacher, Steve Mathis. This shift pushed me away from the humanities I had previously favored and pulled me toward science. Plus, I reasoned that if I had a science-related career, I could support myself and a family.” In college, her physics lab courses were so much more enjoyable than her other labs that she became a physics major.

Her next task was to decide what kind of physics she might pursue. Keller told the Living Histories online series (https:// tinyurl.com/TheLHSeries) in a 2023 talk, “In my sophomore year, I was excited to be chosen to be on a team of students going to Fermilab, [but spent] the summer soldering 4-mi­cron wires 4 millimeters apart on a drift chamber. It was mind numbing. So, particle physics wasn’t as much fun as I had imagined it would be. Neither was astrophysics. My professor kept hitting on me. I did not want to enter a field in which I’d ever have to interact with him again.”

By the time she started graduate school in physics at Prince­ton University, Keller had identified which branches of physics pushed her away, but she had not yet felt a strong pull to any others. Keller shares, “Like most scientists, I can construct a compelling story in which I sound as if I brilliantly planned my training and foundational experiments to amass the right skills and results in the right labs to then answer important questions. However, when I was a student and postdoctoral fellow, I found stories like that demotivating because they im­plied that success in science required an unattainable level of genius and foresight,” she says. “A more accurate description of my career is that I was pulled to work with people I liked and respected, which led me to do my best science because I enjoyed working with them.”

“My single best career move was, as a second-year gradu­ate student, to notice how the members of Sol Gruner’s lab enjoyed each other as much as they enjoyed science, and to decide that I wanted to work with them, even though I had no previous interest in biophysics. Sol proposed a risky project. He hypothesized that ion channels surrounded by lipids shaped like cylinders would function differently than ion channels surrounded by lipids shaped like cones, due to the membrane’s lateral pressure profile. He introduced me to Adrian Parsegian, who introduced me to Sergey Bezrukov, who taught me everything I know about black lipid membranes. Our data showed that Sol’s hypothesis was right, and I pub­lished my first paper in the Biophysical Journal. BJ was the right place to reach broad audiences interested in rigorous physical measurements of membranes, and it still is. I’m honored to be speaking at the BPS Satellite Meeting honoring Adrian on the Friday before the 2025 BPS Meeting.”

Keller recounts, “Attending grad school in the US was a good fit for me. I probably would not have earned a PhD or become a biophysicist in a different academic structure. To afford grad school, I needed a stipend every year, including during my master’s degree. To become a biophysicist, I needed the flexibility to completely change my branch of physics and my research group, even when I was years into my PhD.”

Keller further explains, “Some colleagues and I were inter­viewed in 2021 for Physics Today about why so many women in physics choose biophysics. I bluntly said it was because ‘there are fewer assholes in biophysics,’ which I maintain is still true, and still important. This leads to the question: how can we further increase collegiality among biophysicists, and attract even more talented scientists into our field? Ideas might include nominating broader populations of colleagues for awards, or introducing more colleagues to each other, or trying even harder to recall the dauntingly vast literature to cite each other better. We won’t always succeed—we are busy, tired, and imperfect humans—but good intent seems like the right place to start.”

While Keller was finishing her dissertation, she contemplat­ed possible career paths. She felt that becoming a professor was impossible because when she and other women in her department asked their Chair why there were no tenure-track women on the faculty, he told them that any woman hired would have to be unassailable so that no one could say she had been hired just because she was a woman. Keller told Living Histories, “I interpreted that to mean that [any woman] had to be better than nearly all the men on the faculty. That’s when I stopped thinking I could ever become a professor.”

Nevertheless, she still loved biophysics, and she wanted to apply imaging techniques to biophysical problems. She leveraged her next BPS Meeting to decide what her next move would be. She reveals, “I brought a list of labs doing cryo-electron microscopy to the meeting and asked everyone who the best mentors were. The clear consensus favored Joe Zasadzinski, who is indeed a great mentor! After I joined Joe’s lab, my lab-mate, Ka Yee Lee, told me how much she loved working with Harden McConnell.” As a result, Keller completed postdoctoral fellowships in the Zasadzinski lab at the Uni­versity of California, Santa Barbara, and in the McConnell lab at Stanford University. “In Harden’s lab, I was researching liquid-liquid phase transitions in lipid monolayers, thinking about stripe phases and critical phenomena. I was also gener­ating most of my own research directions. An idea crept back into my head about maybe becoming a professor,” she shared with Living Histories.

Keller told Living Histories that after she began a faculty position at the University of Washington, “the first graduate student to join my group was the brilliant and driven Sarah Veatch. We happened to be doing the right research at the right time. We were trying to find large-scale liquid-liquid phase separation in model lipid bilayers when the first paper showing how this behavior could be achieved was published

in 2001. We were hot on their heels with our papers in 2002 and 2003, measuring transition temperatures and tie-lines. That 2003 paper has been cited over a thousand times now. Sarah convinced her fantastic friend Ben Stottrup to join the group. I might have initially taught Sarah and Ben about phase behavior in lipid membranes, but they got me tenure and taught me how to run a group. They and many other students ‘mentored up,’ and I am so grateful.”

At BPS Annual Meetings, Keller and Veatch connected with Lee, Erin Sheets, Anne Kenworthy, Kalina Hristova, Anne Hinderliter, and Susan Gilmore, forming the Membrane Chix. As Keller told Living Histories, “We didn’t have an Old Boys Network, so we became our own network. We shared stories about which colleagues you could trust and which you should not share preliminary results with,” she explains. “We also noticed that some outstanding senior women in our field had not won major BPS awards. We ganged up on them and encouraged them to apply.”

Keller remarks, “For me, BPS meetings are the annual reunion of my scientific family: through my ‘direct lineage’ of Sar­ahs, my mentor-aunties and -uncles, my science-cousins in related fields, and my brilliant nieces and nephews in the next generation. BPS meetings are important for all our careers because they are where we network to learn the quiet backstory: the experiments that didn’t work, the ideas that weren’t funded, the job offers that were declined, and the collaborations that didn’t continue.”

In addition to her career, Keller enjoys traveling with her partner, Rob Carlson, hiking with her University of Washington colleagues Anne McCoy and Julie Theriot, and making art. The October 1, 2024 issue of Biophysical Journal features an oil painting of Keller’s, highlighting her team’s result that most methods of making giant vesicles incorporate similar ratios of lipids. She also volunteers to broaden voter turnout in elections. One year, she celebrated a student’s dissertation defense by making a cake on the theme of their research, and “thesis cakes” became a lab tradition to highlight and cele­brate the work of her trainees.