It's rare to find a young scientist in a big office, yet Gregory Alushin, age 29, has generous space, a U-shaped desk, and a floor-to-ceiling window with a view of the NIH campus. He is semi-apologetic about the arrangement, insisting that it's only temporary. "We're going to have to leave this place in a few months," Alushin hastily explains. "Another institute had just moved out of this space so we got to be the temporary sole occupants." His lab was founded only seven months ago, says Alushin, and he doesn't want to get too comfortable.
Still, you get the feeling that whoever allocates space, even temporary space, at the National Heart, Lung, and Blood Institute (NHLBI), where Alushin is an Early Independent Scientist, would like him to feel at home scientifically. Alushin, who is an ASCB member, was just named one of Forbes "30 under 30 in Science and Healthcare." He was modest about all this space and attention. "I guess NHLBI decided to nominate me," he says about the feature in Forbes.
During a recent visit to his huge open lab, the only sound was the intermittent squeaking of a sample rotator. Surrounded by lab empty lab bays, Alushin's three employees worked quietly at their benches. Alushin's big office is as bare as his lab. There are only four things on display: three awards, including his 2012 ASCB Norton B. Gilula Memorial Award, and a 2013 photo of himself with classmates and instructors at the Marine Biological Laboratory Physiology Course.
Becoming a PI happened fast for Alushin. After finishing his PhD in biophysics in 2012 at the University of California, Berkeley, Alushin went to the NIH for a postdoc with Clare Waterman, a long-time ASCB member who pushed him in a new direction. "I had the desire to do something that wasn't just working with purified protein doing structural stuff. Clare got me excited about doing some cell biology," he recalls.
Just two months into his postdoc, Waterman showed him the NIH announcement for the new Early Independence Awards, and urged him to apply. "You can only get these grants within one year of finishing your terminal degree," Alushin explains. "They're on the scale of an R01, so you get enough money to run a small lab." Eight months later, he found out he had won the grant.
Now in his own lab, Alushin wants to answer questions about mechanosensation, or the ability of cells to sense their environment through physical cues. "Cells can sense the rigidity of their surroundings; this has a lot of importance in cancer biology. One of the things that will affect whether cells in a tumor will metastasize out of that tumor is how rigid that tumor is," Alushin says. "How cells mechanosense is a big outstanding problem facing cell biology.... One of the ways cells would do that is through changes to proteins that underlie the cytoskeleton."
The cytoskeleton keeps cells rigid, but also helps them move. It's primarily made up of actin and microtubules. "There's been a hypothesis that tension can do things to actin filaments that cells can take advantage of. So we're trying to develop systems to visualize the changes in actin when we apply tension," Alushin says. He wants to use molecular motors that naturally move along actin cables and fix them to a surface. Then he will have actin suspended above the motors with the idea that the motors will stretch the actin. Alushin plans to look at the actin structure using cryogenic-electron microscopy (cryo-EM).
"There's this ongoing revolution in cryo-EM where we're getting to resolutions more like crystallography and I'm trying to get on board with that," Alushin says. Cryo-EM freezes samples at around -190 degrees Celsius (-310 degrees Fahrenheit) with liquid propane or ethane, which have high specific heats. "It freezes the sample so fast that the water molecules can't rearrange and form ice crystals. So it stays vitreous like glass. That's why we can look at the protein molecules," Alushin explains.
Giving a visitor a tour, Alushin descends into the basement of Building 8 where liquid nitrogen hisses as it's poured into the chamber mounted on the cyro-electron microscope to keep samples cold while imaging. The microscope is almost as tall as the room. "It's actually not that big by EM standards," Alushin says. The room is humidity controlled because water is the enemy of cryo-EM. "If you had ice crystals it would just destroy everything."
He takes out what looks like a plastic playing card, except that this card has 120 tiny diamond shaped cut-outs, each one holding a copper disk about the size of the letter "o" in this sentence. "Your sample goes on that tiny thing there," Alushin says, pointing at the copper circle. "They're somewhat difficult to handle." To make things even more difficult, Alushin adds, "Electrons destroy things as soon as they touch them. So you have to get all of your imaging conditions just right, then you get one shot inside of the hole [on the disk]."
While his lab staff works to get the molecular motors project going, Alushin is down in the basement, performing cyro-EM-based structural studies of proteins bound to actin filaments. He's excited about the progress his lab has already made. "We've been able to see the secondary structure of actin," he says.
Alushin predicts that his next and more permanent lab space won't be this grand. But then, he doesn't need a lot of physical room. "I'm a very basic biophysics guy," Alushin says, and he's looking forward to building a lab where cells, molecules, and microscopy can be deployed in new ways to reveal how actin is involved in mechanosensation.