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Biophysicist in Profile

Linda Columbus

Linda Columbus

July/August 2018 // 11500

Linda Columbus, Associate Professor of Chemistry and As­sociate Director of the Global Infectious Disease Institute at University of Virginia, grew up in New Hampshire with young parents. “My parents were 17 when I was born, so I watched them grow up too,” she shares. “My mom inspired me through her actions. In my lifetime, I saw my mom go to high school (I don’t remember that), go to nursing school, go back to college, go to law school, and become a practicing lawyer. Neither my mom nor dad’s parents were educated beyond high school so the concept of an academic life was completely foreign to me until college.”

After graduating from high school, Columbus enrolled in Smith College, in Northampton, Massachusetts, where she majored in chemistry. “Until college, it didn’t dawn on me that I could have a job that was just thinking about science. That level of privilege was not a concept that I had ever been ex­posed to,” she says. She undertook undergraduate research, and her mentors encouraged her scientific pursuits. “Specif­ically, David Bickar and Sharon Palmer at Smith College were very encouraging and at the same time set a bar of intel­lectual rigor,” she says. “I was a chemistry major and I found the physical organic material the most interesting. I enjoyed thinking about how and why organic molecules move, or their differences in stability. Questions like: ‘why is cyclobutane more stable than cyclopropane?’ Or ‘why would a substituent on this ring position change the chair/boat populations in cy­clohexane?’ fascinated me. I was also interested in the yellow stars in the biochemistry textbooks. These stars indicated a conformational change that resulted in the protein carrying out its function. I wrote a paper on the detection of light by rhodopsin and how the signal is propagated and processed by the visual cortex. I assumed proteins were just large organic molecules and that we could understand the conformations of proteins based on what we learned about small organic molecules.”

Following her graduation in 1996, Columbus began her PhD studies in biochemistry and molecular biology at the Univer­sity of California, Los Angeles. She carried out her research in the lab of Wayne Hubbell. “Leaving college, I found myself interested in topics that were grounded in the physical yet applied to the biological, but I was trained as a chemist and didn’t understand that biophysics was a different field. I thought — and to some extent still think — biomolecules are large organic molecules so I didn’t know that physical organic chemistry and biophysics were considered different fields,” she says. “In graduate school, I was able to understand that biophysics went beyond physical organic chemistry. I learned from Wayne Hubbell, my PhD advisor, to dissect biological problems with the different disciplines and that as scientists we could choose and move between the different methods, concepts, and systems. Wayne was an amazing mentor because he let me explore, dig in, and figure things out on my own and was willing to talk about my understandings any­time. Because of these experiences, I didn’t think much about what my next steps were in terms of getting started and pursuing science and biophysics. It was fun so I kept doing it.”Columbus with her husband, Cameron Mura, and son Calvin.

Upon completion of her PhD in 2001, Columbus continued as a postdoctoral fellow in Hubbell’s lab for another year, then moved on to the Scripps Research Institute where she com­pleted postdocs in the labs of Kurt Wüthrich and Scott Lesley.

In 2007, she was hired at the University of Virginia, where she now serves as Associate Professor of Chemistry and Asso­ciate Director of the Global Infectious Disease Institute. Her research focuses on how membranes and membrane mimics stabilize membrane protein folds and how bacterial pathogen membrane proteins interact with human host proteins. The Institute was formed in 2017 with a goal of bringing together researchers from diverse fields to work on urgent infectious diseases, including viruses like Ebola, Zika, SARS-CoV, and MERS-CoV; gastrointestinal pathogens; and antibiotic-resis­tant superbugs.

“The most rewarding and challenging aspect of my work is mentoring,” she shares. “I enjoy helping people realize their vi­sion of what they want to be and giving them the opportunity to find themselves. I take great pride at the amazing careers and experiences my trainees go on to do.”

Alison Dewald, Associate Professor of Chemistry at Salisbury University and one of her first PhD students, shares the influ­ence Columbus has had on her career. “Linda is exceptionally generous with her talents. She was an incredible mentor to me as a graduate student, and has continued to support and advise me throughout my early career. I was recently awarded tenure and promoted to associate professor at a primarily undergraduate institution. This is my dream job, and I owe so much of it to Linda’s mentorship and example,” she explains.

“I became a mother my last year of graduate school. Our uni­versity didn’t have much of a policy for this, but Linda ensured that I was supported with maternity leave and flexibility— she did the same when another student became a father,” Dewald shares. “When I returned to work, she made sure that I (and all future new moms) had a dedicated, private place to pump milk – this hadn’t previously existed in our building. I am grateful for her generosity and support during that time and will be for my entire life; I try to pay it forward when my students have life circumstances.”

Another of Columbus’s former graduate students, Brett Kroncke is now a postdoctoral fellow Vanderbilt University Medical Center (VUMC), and will be starting a tenure-track faculty position at VUMC in the new year. He remembers her influence on him as he began his career. “As my PhD advisor, Linda taught me many things — some technical and some not. It’s hard for me to estimate exactly how important the technical wet lab skills have been, since I rely on them heavily in the experimental side of my research. Linda also insisted on imagining the impact of my project as far into the future as is possible, motivating my research from a big picture potential,” he says. “Linda has been and continues to be extremely sup­portive in my research and career. She pays forward with her time and effort. She has always taken an interest in my career and projects, starting from when I was in her lab to present.”

Columbus with her lab. From left to right, front row: Katie Ahn, Nicole Swope, Linda Columbus. Next row: Jason Kuhn, Tracy Caldwell, Jennifer Martin. Back row: Katherine Lake, Steven Keller, Marissa KieberAs her career has gone on, Columbus has found greater challenge in its secondary aspects than in the science itself. “The biggest challenge is the culture in the different sciences in terms of gender and scientific focus. I have been accused of ‘selling out’ by becoming more biologically focused. I have been asked what ‘hat’ I wear so that I could be classified as a chemist, biochemist, biomedical researcher, or something else,” she explains. “I have been the only woman in a room and I have had numerous campus visits in which I only met with men.” This can feel very alienating, as she explains, “All of these experiences can make me feel like an outsider, different, or excluded. I face these experiences as opportunities to have discussions about the differences I notice without attack­ing an individual. I am usually encouraged by the responses and discussions and find that many people want to increase representation and diversity, but lack tools or opportunities to make changes.”

Columbus advises those just starting out in biophysics to find what they are passionate about and what will keep them motivated, then keep digging. “Always keep asking yourself questions about your data and perspectives in order to dig deeper,” she says. “Don’t report the data chronologically. Ana­lyze data, look at data from different perspectives, and stitch all the data together to tell a story.”

“Linda used to say that if her academic biophysics career didn’t work out, she and her mom would be contestants on The Amazing Race,” Dewald says. “Of course she is so success­ful in her career, but I also think that they could have won the race.”