These days, the lab is learning that glia may have a more important role in nervous system development than anyone ever realized.
Even with such findings, Kucenas will tell you her real mission is to be a helpful guide to students as they pursue their scholarly bliss.
“My own training has been in environments where people just inherently trusted me the first day,” said the scientist, who has directed the lab for 13 years and heads UVA’s Program in Fundamental Neuroscience. “My mentors saw that I was creative and engaged and passionate, while knowing I needed mentorship along the way; I wasn’t a professional scientist yet. So when I started my own lab, it would have been unnatural to do it any other way.”
For her students, just as with the zebrafish, Kucenas creates the conditions for life to unfold in a certain way. In doing so, she’s spawning discovery.
Fishing for New Scientific Knowledge
Kucenas’ office is a celebration of her chosen path. Facing each other on opposing walls are two joyful, swirling abstract paintings of fish. On another wall are snapshots of her former students, intermixed with a few family photos. Her protégés share equal space along a strand of yarn with the moment she introduced her wrinkly newborn daughter, Madelyn, to the world.
Last month, Ashtyn Wiltbank sat beside the array of photos and discussed how she followed her own thread and landed on some important scientific findings. She was a little tired when she spoke to UVA Today, but exceedingly happy. It was the day after she successfully defended her doctoral dissertation.
In 2018, within weeks of joining Kucenas’ lab, Wiltbank had scanned a spreadsheet of tens of thousands of genes – a “snapshot” the lab took of a developing zebrafish using a method called RNA sequencing – and found a gene that seemed to be a worthy candidate for her dissertation study. Having previously worked in labs focused on immunology, she homed in on CD59.
“I saw these genes, traditionally known as immune genes, that were highly expressed in glia,” she recalled.
“… that I had been ignoring,” Kucenas said, equal parts humor and irony in her voice.
“Because you were, ‘Eh, that’s just some immune gene – not interesting.’ And I was like, ‘This is interesting! Like, no one has looked at this!’”
CD59 (sometimes written by scientists as “cd59” in reference to zebrafish) regulates inflammation and protects the integrity of cell walls and membranes from rupture. The gene is useful throughout life for inhibiting cell degradation – from viruses, for example. But little had been known about CD59’s role in the neurological development process.
Looking at the data, Wiltbank could see the gene’s fingerprints were all over myelin – the fatty tissue that insulates nerve fiber in order to conduct electrical impulses efficiently and accurately.
“This was striking because most other cells do not express CD59 during development, whereas during adulthood, most cells in the body do express CD59,” she said.
Her comparisons to other RNA-sequencing databases of developing zebrafish, mice and humans found the same thing: CD59 was highly expressed in the brain and peripheral nerves, and to a lesser extent in two other organs, but otherwise not present in all other cells until adulthood.
So she checked the scientific literature to see what was known.
“There was actually a paper in the 1980s looking at CD59 expression in the brain, and they’re like, ‘It’s really highly expressed in these myelinating cells, and we think it’s important for development.’ But it was one sentence, and nobody has looked at it since. And then I stumbled on this, and I said, ‘I think this is super-important.’
“I suspect a lot of scientists noticed that myelinating glia expressed CD59 during development and just assumed that other cells do as well.”