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Roommates’ exchange fuels research collaboration

Recent Stanford research on the importance of a particular gene in aging can be traced to a casual conversation between roommates.

Stanford MD-PhD student John Pluvinage didn't expect all that much to come of it when he asked his roommate, Benjie Smith, to look at some results he'd been thinking about. As fellow scientists, they often bounced ideas off each other, and Pluvinage figured Smith, a MD-PhD student in Stanford ChEM-H's Chemistry/Biology Interface Training Program, might have some useful insights.

"We'd been talking about our research separately for years," Pluvinage said. "It's nice to get another pair of eyes, so I asked Benjie to look at it."

But in this case, Pluvinage got more than just another pair of eyes: showing Smith his data led to a collaboration between three different Stanford labs -- those of neuroscientist Tony Wyss-Coray, PhD; chemist Carolyn Bertozzi, PhD; and geneticist Michael Bassik, PhD -- and an April 3 publication in Nature. The collaboration also brings together two of Stanford's interdisciplinary institutes, the Wu Tsai Neurosciences Institute, which has supported Wyss-Coray's work on brain rejuventation, and ChEM-H, which Bertozzi co-directs.

As my colleague Bruce Goldman explains in a story for Stanford Medicine News, the researchers identified a gene that plays a role in aging-related cognitive decline -- and they also found a way to reverse that decline in mice.

As Goldman explains, the researchers focused on a particular kind of cell, called microglia -- essentially the brain's garbage collectors -- and why they stop working so well as we get older. To find genes that might explain that, Pluvinage ordered up two screens of about 3,000 genes. One screen was aimed at identifying genes that help microglia eat up the remains of dead cells and other refuse. The second screen was aimed at finding genes whose activity was different in young versus old mice, and genes that showed up in both screens might help explain aging-related decline.

It was those data, originally collected by Bassik's then-graduate student Michael Haney, PhD, that Pluvinage showed to Smith. And when Pluvinage, Haney and Smith looked over the data, only one gene was both more active in old versus young mice and boosted garbage collection when deleted.

But that gene, known as CD22, stood out to Smith in particular. Smith knew that CD22 helps regulate cell functions, possibly including microglial functions, by binding to a sugar called sialic acid -- which just so happens to be the focus of Smith's research. That led the grad students to suspect that sialic acid might play a role in aging-related cognitive decline.

"It was just by chance that I looked at John's list," Smith said, but once he did, "we started to think there was some connection."

As Smith and Pluvinage started looking into the connection, they began to learn more about how cognitive decline works. Smith discovered that sialic acid appears to be key to microglia's function. Increasing the amount of the acid on the surface of microglia decreased their garbage-collecting activity, but only when CD22 was active, hinting that turning off the gene could improve cognitive function. Meanwhile, Pluvinage found that blocking CD22 could increase microglia's activity and halt aging-related cognitive decline in mice.

Together, the results are starting to make the mechanisms of cognitive decline in aging more clear, but "there's a lot of complex questions to follow up on," Pluvinage said. Those questions include why the gene the team identified becomes more active with age, exactly why blocking CD22 improves cognitive function, and, most importantly, whether the results in mice will also work out in humans. They're all questions Pluvinage and Smith are looking forward to working on.

"This project has really kicked off some new things between our labs," Smith said. "John deserves a lot of credit for pushing the work and making it interdisciplinary."

For his part, Pluvinage said his colleagues made that simple. "It's easy to collaborate when you genuinely enjoy hanging out with the people you are working with."

Photo by Startup Stock Photos

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