Some of Princeton’s leading cancer researchers were startled to discover that what they thought was a straightforward investigation into how cancer spreads through the body — metastasis — turned up evidence of liquid-liquid phase separations: the new field of biology research that investigates how liquid blobs of living materials merge into each other, similar to the movements seen in a lava lamp or in liquid mercury.
“We believe this is the first time that phase separation has been implicated in cancer metastasis,” said Yibin Kang, the Warner-Lambert/Parke-Davis Professor of Molecular Biology. He is the senior author on a new paper featured on the cover of the current issue of Nature Cell Biology.
Not only does their work tie phase separations to cancer research, but the merging blobs turned out to create more than the sum of their parts, self-assembling into a previously unknown organelle (essentially an organ of the cell).
Discovering a new organelle is revolutionary, Kang said. He compared it to finding a new planet within our solar system. “Some organelles we have known for 100 years or more, and then all of a sudden, we found a new one!”
This will shift some fundamental perceptions of what a cell is and does, said Mark Esposito, a 2017 Ph.D. alumnus and current postdoc in Kang’s lab who is the first author on the new paper. “Everybody goes to school, and they learn ‘The mitochondria is the powerhouse of the cell,’ and a few other things about a few organelles, but now, our classic definition of what’s inside a cell, of how a cell organizes itself and controls its behavior, is starting to shift,” he said. “Our research marks a very concrete step forward in that.”
The work grew out of collaborations between researchers in the labs of three Princeton professors: Kang; Ileana Cristea, a professor of molecular biology and leading expert in the mass spectroscopy of living tissue; and Cliff Brangwynne, the June K. Wu ’92 Professor of Chemical and Biological Engineering and director of the Princeton Bioengineering Initiative, who pioneered the study of phase separation in biological processes.
“Ileana is a biochemist, Cliff is a biophysicist and engineer, and I am a cancer biologist — a cell biologist,” Kang said. “Princeton is just a wonderful place for people to connect and collaborate. We have a very small campus. All the science departments are right next to each other. Ileana’s lab is actually on the same floor of Lewis Thomas as mine! These very close relationships, among very diverse research areas, allow us to bring in technologies from many different angles, and allow breakthroughs to understanding the mechanisms of metabolism in cancer — its progression, metastasis and the immune response — and also come up with new ways to target it.”