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Biomolecular condensates for beginners—and aliens

Imagine that you’re an alien scientist spying on Earth, and you have a telescope that lets you examine Manhattan and its rows of towers. You know these buildings must be important, because using your X-ray settings, you can see that each building has many levels, and that thousands of tiny dots move around busily inside each level. Specific levels are divided up into rooms—some small and closed off, some large and open. But your telescope doesn’t have enough power to show what the little dots do inside these rooms. So the full purpose of the dots and their buildings remains a puzzle.

Then you invent an improved lens that lets you resolve individual dots. It turns out that they spend a lot of time bouncing around their levels, seemingly at random. But once in a while, they come together in clumps that last for minutes to hours. The clumps have different sizes, and they can form in the closed rooms or the open areas.

After observing many dots in many buildings over a long period, you begin to notice a pattern. The buildings where clumps form and disperse at frequent, regular intervals seem healthier, in a sense: they last longer before being demolished. But if the clumps form too often or last too long, the opposite occurs.

Congratulations. You have discovered one of the engines driving—and sometimes plaguing—Earth’s economy: the business meeting.

There are no perfect metaphors in science. But if you think of the body as an office building divided into floors (cells), and of proteins and other cellular workhorses as company employees who must meet up periodically to advance their work, it can begin to help you understand an important but mysterious phenomenon that is now beginning to be exploited for pharmaceutical research: the biomolecular condensate.

Condensates themselves aren’t breaking news. They’ve been known under other names since at least 1903, when the pioneering neurobiologist Santiago Ramón y Cajal became one of the first researchers to document them under the microscope. But until recently there were few established facts about these enigmatic bodies, which is why they went by vague, impressionistic labels such as “Cajal bodies,” “P-bodies,” “Lewy bodies,” “P granules,” “stress granules,” and “paraspeckles.”

All that was really known was that condensates, unlike classic organelles such as nuclei, mitochondria, or lysosomes, lacked the lipid membranes needed to permanently separate them from their surroundings. Also, they could appear anywhere: inside the nucleus, close to the cell’s essential cargo of DNA, or outside it in the wider cytoplasm. They were able to come and go, coalescing as if from nothing and just as quickly disappearing. And sometimes they caused trouble, jamming up a cell with unneeded structures and debris. They were the poltergeists of cell biology.

But beginning in the late 2000s with the work of Tony Hyman and Clifford Brangwynne, biologists at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, Germany, condensates became a lot less ghostly. Scientists began to notice a few things about these bodies that explained their odd behavior, and that hinted at their important, underappreciated roles in the lives of cells…

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