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Sloppy science or groundbreaking idea? "Phase separation" divides biologists

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https://www.sciencemag.org/news/2021/01/...ts-divides

INTRO: For 7 years as president of the Howard Hughes Medical Institute, Robert Tjian helped steer hundreds of millions of dollars to scientists probing provocative ideas that might transform biology and biomedicine. So the biochemist was intrigued a couple of years ago when his graduate student David McSwiggen uncovered data likely to fuel excitement about a process called phase separation, already one of the hottest concepts in cell biology.

Phase separation advocates hold that proteins and other molecules self-organize into denser structures inside cells, like oil drops forming in water. That spontaneous sorting, proponents assert, serves as a previously unrecognized mechanism for arranging the cell’s contents and mustering the molecules necessary to trigger key cellular events.

McSwiggen had found hints that phase separation helps herpesviruses replicate inside infected cells, adding to claims that the process plays a role in functions as diverse as switching on genes, anchoring the cytoskeleton, and repairing damaged DNA. “It’s pretty clear this process is at play throughout the cell,” says biophysicist Clifford Brangwynne of Princeton University.

The pharmaceutical industry is as excited as some academic researchers, given studies linking phase separation to cancer, amyotrophic lateral sclerosis (ALS), diabetes, and other diseases. [...]

Tjian says he was agnostic at first about the importance of the process. But after McSwiggen’s findings inspired him and colleagues to look more closely at the range of claims, the researchers began to have doubts. Tjian and a camp of similarly skeptical biologists now argue that the evidence that liquidlike condensates arise naturally in cells is largely qualitative and obtained with techniques that yield equivocal results—in short, they believe much of the research is shoddy.

Moreover, the contention that those intracellular droplets perform important roles “has gone from hypothetical to established dogma with no data,” says Tjian, who stepped down as president of Howard Hughes in 2016 and now co-directs a lab at the University of California (UC), Berkeley. “That to me is so perverse and destructive to the scientific discovery process.”

Although proponents of phase separation bridle at some of those criticisms, many scientists agree that the research requires a jolt of rigor... (MORE - details)
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