Cliff Brangwynne describes himself as a late bloomer in science, not developing a strong interest in the subject until his later teen years. Once he learned about the unsolved mysteries inherent to the field, he couldn’t wait to learn more—and he has spent his career as a biophysical engineer doing just that.
Brangwynne was raised in the Boston area in the same house in which his mother grew up. “As a kid I went to a Catholic school that was basically across the street from my house in Boston—if you’re picturing some of those Ben Affleck-Matt Damon movies of working class Irish-Catholic Boston, that’s not too far off,” he jokes. His big family did not include any scientists when he was a child, but there are several in his generation. “I have a large extended family full of electricians, plumbers, painters, and nurses—a wonderful, loving, and high-energy (read: loud) bunch. None of that generation graduated from college, but my mom in particular had this strong appreciation for the value of education. And for some reason my sister and I, and several of our cousins, became scientists,” he shares.
Brangwynne had no particular interest in science as a child, but dove in during his later high school years. “I was a bit of a ‘late bloomer’—no chemistry sets in the basement or math team Olympiads,” he remembers, “but sometime in the middle of high school I started reading pop-science books about quantum mechanics and became aware of these mysterious and unsolved problems at the root of our physical world. I enjoyed thinking about this and wanted to learn more.”
He attended Carnegie Mellon University, from which he graduated with a bachelor’s degree in materials science and engineering, minoring in physics. “Probably the biggest struggle of my career was getting started during the college years. I was pretty resource-challenged in college and led a sort of threadbare bohemian existence. I was also not really sure how to combine my different interests, and where that would lead,” he recalls. “I knew I liked physics and engineering, but I also was fascinated by biology. In the beginning, it wasn’t at all clear to me how to combine these, because at the time I couldn’t find many people working at this interface. But I think I was able to manage this uncertainty with the help of some terrific mentors—if you’re a young aspiring scientist unsure of how to get started, step one is to find a good mentor who can give you advice. Many people have themselves had great mentors and are eager to pay it forward.” He continues, “I was able to overcome some of this uncertainty by letting my curiosity about the natural world guide me—I pursued research because it seemed interesting, not because I thought it might be a good career or impress anybody or something. Slowly I started to see how to bring my different interests together in a fruitful way.”
Following his graduation, he earned his PhD from Harvard University in applied physics. Brangwynne then undertook a postdoctoral position in Dresden, Germany at the Max Planck Institute for Cell Biology and Genetics, spending some of his time at the Max Planck Institute for the Physics of Complex Systems. “There I began studying this interesting class of intracellular organelles that don’t have an enclosing membrane. During this time, I was fortunate to make an important discovery about these structures, showing that they represent condensed liquid states of biomolecular matter, that form through a kind of intracellular phase transition known as liquid-liquid phase separation,” he explains.
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, particularly how phase separation drives compartmentalization and function within cells. We use approaches from materials science and soft matter physics, combined with cell and molecular 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 materials physics and cell biology. My findings on the liquid nature 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 aspect 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 underlie 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 Blavatnik 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 understanding but also engineering cells for human health. People 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 papers, 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 together 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 shorthaired 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.”