Cell biologist Amy Gladfelter, PhD, has been intrigued by a fungus called Ashbya gossypii for 20 years. Made of branching strands, this mold consists of “giant” cells packed with multiple nuclei. In 2006, she showed that none of these nuclei divide at the same time. At the time, this independent division inside a single cell went against everything scientists thought they knew about how cells operate.
Now Gladfelter’s team at the Duke University School of Medicine has shown how Ashbya keeps division and growth organized: by using tiny “popup” biochemical compartments made from a protein called Whi3.
Whi3 combines with specific RNAs to form small, liquid-like droplets, called condensates. The condensates gather proteins that regulate translation — the process of making proteins from RNA. Positioned strategically near nuclei and at the growing tips of the cell, the droplets help control exactly which RNAs are translated in each location.
“Condensates literally condense like dew on grass. The molecules go from being like a gas to more like a droplet. They create a space for biochemistry to occur.” — Amy Gladfelter, PhD
“Condensates literally condense like dew on grass,” said Gladfelter, Duke Health Distinguished Professor of Cell Biology and Biomedical Engineering. “The molecules go from being like a gas to more like a droplet. They create a space for biochemistry to occur.”
In the lab, two postdoctoral research associates, Zachary Geisterfer, PhD, and Ameya P. Jalihal, PhD, found that Whi3 droplets could tune translation up or down depending on the RNA they contained and the size of the droplet. The study, published in Nature Cell Biology, shows that condensates create separate translation “zones” that help the fungus control when its cells grow and divide, even when several rounds of growth and division are happening at once in the same cell.
Many condensate-forming proteins are what biologists call “disordered”— they don’t settle into a single shape. “They sample a whole bunch of conformations,” Gladfelter said. Although such flexibility is often linked to disorders like Huntington’s, in Ashbya it plays an organizational role. “They’re able to appear and disappear,” she said. “And they allow this dynamical tuning.”
The system isn’t without risk. If condensates grow too large or lose their ability to dissolve, they can become “sticky,” leading to stress that strains the cell’s quality-control machinery, Gladfelter said.
Still, the findings showcase the versatility of fungi — and how even cells that seem disorganized at first glance maintain tight control of their growth and division through finely tuned molecular structures.
Next, Gladfelter’s lab will explore questions raised by these findings, including how each nucleus knows that it’s time to divide. Dozens of nuclei may lie between a condensate and the nucleus that divides, yet the correct one somehow gets the signal. “What is that signal? How is that relayed at such a distance? It would be like you’re waiting in line, and there’s 50 people in front of you, but you know, somehow, what’s going on at the front of the line,” she said.
Though Gladfelter didn’t know it 20 years ago, asynchronous division guided by condensates turns out to be a broader principle of cell organization — seen not only in branching fungi but also in skeletal muscle, the placenta, and neurons. “NIH invested in me before we knew how general this organization was,” she said.
Other Duke authors: Sierra J. Cole.
Funding: Air Force Office of Scientific Research, the National Institutes of Health.