Biophysical Society Bulletin | July/August 2018

Biophysicist in Profile

Linda Columbus Areas of Research Membrane protein structure, dynamics, folding, and function

Institution University of Virginia

At-a-Glance

Before she went to college, Linda Columbus did not know it would be possible to have a career as a scientist. “I loved puzzles and challenges, but I wasn’t sure how that fit into a career. Now I see exactly how it fits into being a scientist.” She now applies her problem-solving skills in her research on how membranes and membrane mimics stabilize membrane protein folds and how bacterial pathogen membrane proteins interact with human host proteins, and in her role as Associate Director of UVA’s Global Infectious Disease Institute.

Linda Columbus

Linda Columbus , Associate Professor of Chemistry and As- sociate 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 ex- posed to,” she says. She undertook undergraduate research, and her mentors encouraged her scientific pursuits. “Specif- ically, David Bickar and Sharon Palmer at Smith College were very encouraging and at the same time set a bar of intel- lectual 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 cy- clohexane?’ 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 Univer- sity 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 any- time. 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.” 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 com- pleted 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 Asso- ciate 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-resis- tant superbugs.

July/August 2018

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