Opposites Attract

When Josie Clowney (B.S. ’05) was an undergraduate studying biology, she lost a lot of shoe leather walking between science lectures and labs in the Natural Science Building to the Student Activities Building, where she worked at WCBN, the student-run radio station on campus. The kind of thinking she needed to put together an afternoon of tunes was a nice counterbalance to her academic work. “But WCBN actually informed my scientific development more than anything else,” Clowney says. “There, the cool thing was what wasn’t a trend. If you were into what everybody already knew about, it was probably too conventional.”

Now assistant professor in the Department of Molecular, Cellular, and Developmental Biology, the same department from which she graduated, Clowney has brought the kind of flexible thinking she developed from WCBN into her lab. As a professor, Clowney teaches undergraduates and runs a developmental biology research lab. She and a team of trainees are working to understand how information in DNA patterns the development of the brain to enable meaningful interactions with the vast and ever-changing world.

Clowney approaches science from a humanist perspective. The questions at the heart of her research explore the matter of life, unconstrained by the need to solve a utilitarian problem. “In a liberal arts setting, we’re able to think about science, anatomy, animals, and bodies and be guided by a spirit of inquiry to understand the natural world,” she says. “It’s incredibly beautiful.

“Essentially, I’m interested in how it’s possible for us to have a human body,” she continues. “The process of generating an organ is particularly complex for the brain, where development translates information in the DNA into a three-dimensional structure of interconnected neurons. The resulting structure allows us to interpret environmental signals and use them to make meaningful decisions.”

So Much From So Little  

The projects Clowney leads in the lab are varied. Her studies range from the evolution of genes, to neural circuits, to sex differentiation. At a glance, it can be difficult to tease out the connections between them, but Clowney sees a common theme. “My work is motivated by thinking about development as a logic puzzle.”

In one study, Clowney investigates sex differentiation in the brain, with research questions emerging from a fundamental interest in how the brain develops. “In this context, sex is interesting because biological distinctions in the brain allow males and females to respond differently to the same environment,” she explains. “The neurons between male and female brains are mostly the same—only about five percent of neurons are sensitive in their development to the sex of the organism. But the influence of the animal’s sex on the development of those neurons leads to very precise differences that allow for sex-typical behaviors.”

The established understanding of sex differentiation in the brain suggests that sex-specific neurons are added on top of sex-shared neurons. The research underway in Clowney’s lab, which recently received funding from the Pew Charitable Trusts and the McKnight Foundation, could flip that assumption on its head.

In mammals and insects, Clowney explains, a signal in the brain called a transcription factor initiates the masculinization process, but there is no analogous factor in females. “That made me and a Ph.D. student in my lab, Margarita Brovkina, wonder, ‘Could it be that development makes everything for both sexes, everything that either sex will need? And then there’s this active mechanism that removes female-specific elements from males?’

“If we’re right and the default in brain development is to make everything for both sexes, that means you get to use the entire genome to do that development work,” Clowney continues. Asking a single sexing transcription factor to do all of the sex-differentiation work seems like a lot to ask from a single gene. But if all the genes in the genome do all the work of building up the brain first, then this sex-giving transcription factor only has to break a few things and protect others from being broken. “That seems more possible,” Clowney says. “It’s easier to break things than it is to build them.”

For now, Clowney and her team, which includes Brovkina and Ph.D. student Najia Elkahlah (B.S. ’18, M.S. ’20), are still exploring these questions and are not ready to draw any conclusions. “I think the true picture is going to be a lot more complicated, as things always are,” she says. “The way I think about these questions is from the point of view that evolution is a huge mess. I want to know how these circuits get built. How can development efficiently interpret all of the information in the genome? How can we make so much from so little?”

They’re questions that come, at least in part, from the ability to approach problems from an unexpected angle, which Clowney attributes to her undergraduate days and the “punk ethos” that defined WCBN when the coolest music to listen to “was what nobody knew about.”

It’s a stance that continues to inspire her approach to scientific questions, too. “In science research, which by nature must take place at heavily funded institutions, an underground isn’t really possible because you can’t do research without certain structures and resources,” she explains. “But having that point of view about venerating the underground has still really helped me separate how I decide what’s interesting from what’s popular. To be able to say, it’s not necessarily wrong if people don’t get it at first, has been really freeing.”

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Illustration by Becky Sehenuk Waite