Michael Levine Awarded 2015 Conklin Medal

By Marsha E. Lucas

The 2015 Society for Developmental Biology Edwin G. Conklin Medal was awarded to Michael Levine of Princeton University for his extraordinary research contributions to the field of developmental biology and training of the next generation of scientists. Levine’s extensive work uncovering transcriptional mechanisms in developing fly and sea squirt embryos has enhanced our understanding of gene regulation and evolution. As a postdoc with Walter Gehring, he and William McGinnis discovered the homeobox protein domain. Later, as an independent investigator, Levine’s group systematically dissected the even-skipped (eve) stripe 2 enhancer to show how discreet stripes of expression depend on the integration of broadly expressed transcriptional activators and locally expressed repressors. In addition to work on Dorsal morphogen gradient thresholds and shadow enhancers, his group has taken up evo-devo studies in Ciona in an effort to understand vertebrate innovations like the neural crest and cranial placodes.

Levine’s interest in development was piqued as an undergraduate student in Fred Wilt’s developmental biology class at the University of California, Berkeley. In an interview last Spring, Levine said the sea urchin molecular biologist was an “absolutely inspired teacher.” Wilt’s “raw enthusiasm” and willingness to teach not only what was known in 1975, but also discuss the future frontiers, convinced Levine that the field of developmental biology was poised for tremendous discovery. “He just completely defined what I wanted to do,” Levine said.

After Berkeley, Levine headed to Yale University for graduate school where he joined the lab of bacterial geneticist, Alan Garen. Garen, famous for identifying some of the first stop codons in bacteria in the 1960s, switched to Drosophila in the early 1970s. “The lab was pretty small,” Levine said. “So, I had a lot of individual attention from him. Sometimes more than I wanted.”

As an advisor Garen was quite critical, so Levine had to bring his A game when discussing his research with him. "It was kind of a tough experience because he was really hard core and old school, but I look back and realize that that was extremely rigorous training. It was just intellectually rigorous."

Levine’s graduate work on genome modifications in developmentally regulated Drosophila genes, along with a friendly call from his advisor to the biology chair at Columbia University (Cyrus Levinthal), earned him a faculty job offer before he even graduated from Yale.

Fortunately, they suggested he do a postdoc before coming to Columbia, otherwise, he might have missed out on one of the most fruitful collaborations of his career. Levine went to the University of Basel to do a postdoc with Walter Gehring. There he met two of his closest scientific colleagues—Bill McGinniss and Ernst Hafen—and together they discovered the homeobox protein domain found in homeotic genes which control the fly body plan. “It was just really fun working with those guys,” Levine said. “I didn’t realize at the time but that was probably the single most exciting period I would have in science.”

After a short postdoc at UC Berkeley with Gerry Rubin, Levine joined the faculty at Columbia in 1984. In 1991, he moved to the UC, San Diego and six years later he became a professor at his alma mater, UC Berkeley.

As Levine moved up the ranks of academia, he credits the informal mentorship of fellow fly guy, Peter Lawrence, with making him a better science communicator.

“Peter is a guy who really values the scientific community and has always reached out to younger people,” Levine said.

“Peter heard me give talks and he said, ‘This is really important stuff but you’re not communicating it very well.’” He helped Levine write better papers and give better talks.

“I look back at that and I just think, Wow, who ever does that? It was rare then. And it’s nonexistent now. And I’m just really grateful to him for that.”

At Berkeley, Levine was widely regarded as one of the best teachers in the Molecular and Cell Biology Department, something he worked hard at because he had such great teachers as a student there.

As for his personal mentoring style, Levine admits, “I’m not always the calmest, most rational mentor with the students and postdocs in my lab.”

He has extremely high expectations and would prefer they eat and breathe their science. The best ideas, he said, often come when you least expect it—like in the shower or taking a walk. Those are not times to be planning what movie to see, but rather, what your next experiment should be.

“I guess that’s a little hard core. But that’s my—that’s kind of my deal [laughter],” he said.

Many of Levine’s former trainees have gone on to exceptional careers of their own. The most rewarding part of his job is when a student or postdoc surprises him with some interesting result.

About a year ago his graduate student, Jacques Bothma, and rotation student, Gavin Schlissel, knocked on his office door to show him a movie they made of eve stripe 2 expression in living Drosophila embryos. From one to three hours after fertilization you see individual nascent RNAs produced from the eve stripe 2 enhancer. Expression is initially broad; then a stripe forms; and then it quickly disappears.

“For me that was almost a religious experience. It was so beautiful,” he said. “After doing in situ hybridizations for 30 years and always trying to imagine what it would look like if we could ever do this in a living embryo. I can tell you the whole thing was much faster than I ever was able to replay in my head.”

This summer after 19 years at the University of California, Berkeley, Levine became the new director of the Lewis-Sigler Institute for Integrative Genomics at Princeton University.

Winning the Conklin Medal was particularly special for him because Conklin, a sea squirt developmental biologist, is one of his science heroes. “Conklin taught us the importance of lineages in producing complex tissues, organs, and structures,” he said.

“My overarching research has really been focused on transcription mechanisms in the fly embryo. But, I just can’t shake my love of that sea squirt embryo. I mean, I really like it. It’s in a sweet spot on the evolutionary tree of life...it’s freaking outstanding.”

His lab is now split about 50:50 between Drosophila and Ciona research. He would like scientists today to remember Conklin’s contributions from the classical era of developmental biology.

“We haven’t done Conklin as proud as the frog guys have done [Hans] Spemann. But, eh, maybe we’ll turn the tide?”