Biophysical Society Bulletin | November 2021

Biophysicist in Profile

In 2011, he joined the faculty of Princeton University, where he is currently the June K. Wu ’92 Professor of Chemical and Biological Engineering and a Howard Hughes Medical Institute Investigator. “My lab at Princeton focuses on understanding the biophysical principles of intracellular organization, partic- ularly how phase separation drives compartmentalization and function within cells. We use approaches from materials sci- ence and soft matter physics, combined with cell and molecu- lar biology techniques, to understand and engineer living cells. This work is really exciting and meaningful to me because it weaves together the two threads of my prior training, in ma- terials physics and cell biology. My findings on the liquid na- ture of P granules were the productive collision of these two threads,” he explains. “My research falls into a few different areas related to emergent intracellular organization. One as- pect of this is genomic organization, where phase-separated biomolecular condensates are forming in, on, and around the genome, in ways we don’t really understand. A second area of interest is in protein aggregation disease, where liquid-like condensates seem to gel or solidify, which appears to under- lie pathologies such as ALS and Alzheimer’s. A third area is in technology development, where we try to come up with new ways to probe and engineer the phase behavior in living cells, with the potential for various applications in biotechnology and therapeutics.” Brangwynne has received several prestigious awards for his work, including a MacArthur Foundation Fellowship, the Blav- atnik Award for Young Scientists, the Human Frontier Science Program Nakasone Award, and the Wiley Prize in Biomedical Sciences. “Biophysics is fascinating because, of course, cells obey the laws of physics!” he says. “For that reason, biophysics has broad applications. I’m increasingly interested in not only un- derstanding but also engineering cells for human health. Peo- ple started referring to me as a ‘biophysical engineer,’ which is a term that I kind of like, in that we’re both asking, ‘What

is the underlying biophysics at play in cells?’ and also asking, ‘How can we translate that knowledge into bioengineering approaches that exploit the underlying physics?’” The most rewarding part of the work for Brangwynne is working collaboratively to bring an idea to fruition. “I like constructing things—treehouses, short stories, scientific pa- pers, research programs. To me, one of the most exciting and rewarding aspects of being a PI is to share a vision, assemble a team, and try to inspire them and work together with them to make the dream into a reality,” he shares. “Working togeth- er with students and postdocs and watching them learn and grow through the process is particularly meaningful.” One of his fondest memories from the BPS Annual Meeting is sharing convention center space with a tattoo convention. “Right at the boundary was the room hosting one of the first meetings of the Intrinsically Disordered Proteins (IDP) Subgroup. I recall thinking this appropriate, since both were sort of outcasts!” he jokes. “Years later, a lot of my lab’s work started to intersect strongly with IDPs, so I look back on that first encounter with IDP scientists and laugh.” When he is not working, Brangwynne spends his time with his family. He also has several hobbies, including ice hockey, jogging, and trail running, the latter with his German short- haired pointer. “I also like to fish—and sometimes even catch them,” he jokes. “I occasionally make noise on the banjo and ukulele.” To early career biophysicists, he advises: “Pay attention to the things that you find the most interesting. If you dive deep and become fully immersed in some area or set of questions that you find you are passionate about, you are going to make progress and see new things that have not been seen before. I do take into consideration the big picture, and try to position my work strategically, but mostly I just do things that I think are interesting and cool, and the rest seems to sort itself out.”

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November 2021

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