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Inaugural Elizabeth D. Hay New Investigator Award Presented to Maria Barna

By Marsha E. Lucas

Maria Barna (left) with her former graduate advisor Lee Niswander.

Maria Barna, Assistant Professor of Genetics and Developmental Biology at Stanford University, received the inaugural Society for Developmental Biology Elizabeth D. Hay New Investigator Award for her outstanding research in developmental biology during the early stages of her independent career. Barna’s work on translational control of gene expression through ribosome specificity has put her in a class of her own. She showed that a mutation in a specific ribosomal protein (RPL38) disrupted protein synthesis in a subset of Homeobox mRNAs resulting in tissue-specific patterning defects. She then showed that regulatory elements within the 5’ untranslated regions of those Hox genes are required for this ribosome mediated control of gene regulation. Recent work using ribosome profiling showed that key developmental pathways like Shh and Wnt are under an unexpectedly high level of translational control.

Barna earned her Bachelor’s degree in anthropology at New York University in 1998. Her first biology course at NYU was a graduate level immunology course led by Carol Reiss. Having taken AP Biology in high school and needing another science course, Barna convinced Reiss she could handle the journal club style advanced course.

“That was maybe the best thing that could have happened because it gave me exposure to reading primary literature in science. And then I got hooked,” Barna said in a July interview.

Sensing her excitement about science, Reiss invited Barna to work in her lab to study how viruses are cleared from neurons.

“I was able to do a lot of really interesting research thanks to Carol at a relatively young age and with great independence.”

Barna may be the only anthropology major in the history of anthropology majors to graduate with seven peer-reviewed publications including two first author papers on viral infections in the central nervous system.

Unsure about a career in anthropology or biology, Barna delayed graduate school and started working as a technician in the lab of cancer geneticist, Pier Paolo Pandolfi at Memorial Sloan Kettering. His lab generated mice with a null mutation in the promyelocytic leukemia zinc finger (Plzf) gene to see if they would develop leukemia. Unexpectedly, these mice had “funny looking limbs.”

Since Pandolfi was not a developmental biologist, Barna almost immediately began collaborating with Lee Niswander.

“I just remember [going] to her office with these skeletons and saying, ‘Lee, what do you think?’ And us kind of brainstorming what to do,” Barna said.

This side project led to one of the most meaningful mentoring relationships in Barna’s life and to discovering her love for developmental biology.

In 2001, Barna entered graduate school at Cornell University’s Weill Graduate School of Medicine and joined Lee Niswander’s lab at Sloan Kettering. She continued to study the role of PLZF in limb and axial patterning.

When Niswander moved her lab to the University of Colorado in 2004, Barna stayed on the East Coast to finish her degree. For three years she worked independently with the support of her advisor, completing her doctorate in 2007.

Instead of doing a traditional postdoc, Barna was accepted into the Sandler Fellows Program at the University of California, San Francisco where she established her own independent research program. This brought her into the purview of legendary mouse geneticist Gail Martin. Martin didn’t like that Barna’s lab was isolated from other developmental biologists.

“I remember Gail just coming to my office one day and saying, ‘I think it’s better that you’re closer to me.’ And I was like, ‘Oh, my god that would be my biggest dream.’ And so she actually carved out space from her own lab to allow me to have a small lab close to her,” Barna said.

Martin offered Barna tremendous support during her time as a Faculty Fellow and she greatly benefited from their joint lab meetings. It was a stressful time for Barna because her science immediately began going in an unexpected direction.

“[The science] was pointing me to a very new mechanism for gene regulation. And it was an incredibly hard problem. It kind of went against everything that was ever written in any molecular biology textbook,” she said.

How does a mutation in ancient translational machinery—the ribosome—give rise to defects in a cell type specific manner and affect the expression of genes with such specificity and selectivity?

“I was scared because I was really following the lead of the science and not allowing myself to be biased by anything else besides what I was seeing in front of me. But, it was also very, very risky. So, I remember thinking—back when I was a fellow and I had a very small lab with only a couple of people—that I can shelter this risk. I have this unique opportunity where I have funding to maintain a small lab without having to write grants, without having to teach, and just focusing on the best science that I can do.”

Barna needed to develop new methodologies to test her “crazy ideas.” Her group spent many years working on this at UCSF and then at Stanford where she became a faculty member in 2012. Today, she is finally seeing the fruits of that labor.

“The most gratifying moment of my career is being at a point [now] where we have the tools, techniques, and evidence to really make this super hard question a tractable one,” she said. “And I’m so excited by that because I think the next couple of years—it’s hard to predict where things will go—but I feel confident that we can test this grand hypothesis that we have that there is this important new layer of control to gene regulation.”

Barna expressed appreciation for the support she has received throughout her career.
“I have been so blessed with wonderful female mentors,” she said. In addition to Reiss, Niswander, and Martin, she is inspired by Stanford professor, Lucy Shapiro who studies asymmetric cell division in bacteria. After a career of more than fifty years, “she’s still doing cutting edge science,” Barna said. “She has so much energy.”

As for her own mentoring style, Barna said, “I really want people in the lab—similar to what was afforded me—to develop their own independence and for me to really be a champion or supporter of their ideas.”

She strongly encourages collaborations amongst members of her lab too. She has biochemists, RNA biologists, geneticists, developmental biologists, and computational biologists in her lab. “I think that all of them individually could never come and do as beautiful science as they could in concert with each other.” She often has papers with two or three co-first authors. This kind of research style requires trust among colleagues, she said. “Together they are able to broach a problem in a completely unique way that neither of them individually could do.”

Barna has been awarded the American Society for Cell Biology Emerging Leader Prize and the Genetics Society of America Rosalind Franklin Young Investigator Award. In 2014, she was named an Alfred P. Sloan Fellow, a Pew Scholar, and was listed as a Top ‘40 under 40’ by Cell Press.

Being awarded the inaugural Elizabeth D. Hay Award was “such an incredible honor,” she said. “This was the first time that . . . when I went up to the podium, I was really emotional. And I normally am not. It took me a couple minutes to be able to regain my thoughts for the talk.”

Barna has a long relationship with the Society for Developmental Biology. She gave her first talk as a graduate student at an SDB meeting.

“The [SDB] community kind of creates this warm blanket where you feel there’s incredible appreciation for junior scientists,” she said. “My greatest heroes of science are developmental biologists. To be awarded the first [Hay] Award was just monumental for me.”

Watch Maria Barna's 2017 Elizabeth D. Hay Award Lecture here.