Search Magazine June 16, 2016

Discovery and closure

Steven Munger, Assistant Professor at The Jackson LaboratoryPhoto by Tiffany Laufer

Assistant Professor Steve Munger’s long road to embracing research and a life of open-ended questions

Part of research is failure.

That can be daunting for many people. An extraordinary amount of work goes into designing and carrying out experiments, most of which don’t pan out, at least not as hoped or expected. But it’s not failure that fazes Steve Munger, Ph.D. Instead, his greatest challenge is achieving something else that science rarely provides: completion and closure.

“There are always new questions to answer,” Munger notes, “so there’s a part of science that never ends. That can be difficult for me, because I really need to feel like I’ve finished something. Day to day, though, it can be as simple as cooking dinner. I love to cook, and if I make a good dinner, I’ve completed something worthwhile that day.”

And when major milestones loom, like his recent faculty candidate seminar at The Jackson Laboratory, he takes it up a notch or two. “I got so many household projects done the weekend before my faculty interview at JAX!” says Munger, now an assistant professor in Bar Harbor. “I didn’t sleep much, but that’s how I work best. I may have my top priority, the thing that I need to work on the most, but if I can complete and check off other smaller things lower on the list, the big things tend to go much better in the end.”

Failure to launch

Munger’s path to high scientific achievement started like that of many others, as valedictorian of his rural high school. But after that, it had more than its share of twists and turns.

“I just wanted to get out of my hometown, Beaverton, Mich., and do something big,” he says. “The local paper always interviewed the valedictorian, so I told them I wanted to be a heart surgeon off the top of my head. It sounded cool. But we didn’t have high-level math or science in school, so I really had no idea.”

Matriculating in the honors college at the University of Michigan, Munger’s big-fish- in-small-pond to minnow-in-big-lake transition did not go well. He was kicked out of the honors college within a year, and while he hung in well enough to graduate, he acknowledges that he never did take full advantage of his opportunities or learn “how” to go to college. He left Ann Arbor with a biology degree but still little in the way of study skills, ambition or prospects.

After graduating, Munger crashed on couches with friends and family and bounced around working short-term jobs. Stints as a substitute teacher, bowling alley attendant and Mongolian barbecue cook provided no insights, and he remained without direction. Eventually, he found himself having to move back to his mother's home in Beaverton, the town he’d tried to escape. It was, he admits, “humbling.”



Catching the bug

Unexpectedly, the job search in his hometown provided the springboard Munger needed. He applied to a temp agency that happened to provide staff for the Dow Chemical Company, and he wound up joining a small team working on early organic LED displays. The group, headed by a physicist (a classic “mad physicist” according to Munger) was developing and testing polymers for color, durability and other factors that could produce full-color displays. It was in the lab that he “caught the research bug.”

“I’d never done real research as an undergrad, so it was a new experience,” says Munger. “But the potential of the project was noticed early on, and we quickly went from a group of six to more than 50. I found myself overseeing a testing lab of 10 people within a year and a half. It was such a fun time. I felt like I belonged in this high-powered peer group.”

Among the lab newcomers was a young woman named Heidi, who, like Munger, originally saw working there as an interim step. They began dating and soon became engaged. In the meantime, Munger discovered that while a lack of an advanced degree didn’t affect his standing in the lab with his peers, it did when promotions came out. To improve his prospects he took a job in quality control, but he found the work unrewarding. He was four or five years out of school with a fiancée and a good job that paid the bills, but he found himself unfulfilled again. It was time for a change.

Back to school

Munger decided to pursue a graduate degree, but in what? Polymer chemistry didn’t appeal to him long-term. He had his biology degree and a continued interest in the subject — the sequencing of the human and mouse genomes had caught his eye in the news — so on something of a whim he decided to pursue genetics. His graduate school choices included Michigan, but the appeal of a change of scenery had the young family — by then with a six-week-old daughter — making the long drive to Duke University, in Durham, N.C. Two weeks after arriving in town, Munger started his grad program.

It did not go well.

“My daughter, Grace, was colicky, so sleep was hard to come by,” he says. “And while I was the second oldest student in my class, I was the least prepared. After two lab rotations I was doing very poorly and was ready to leave — I didn’t even schedule my third rotation.”

But in one of his courses, a professor in the department, Blanche Capel, taught mouse genetics, and Munger enjoyed the section and did quite well on the test. When Munger went to pick up his exam, Capel asked his plans and convinced him to join her lab for his third rotation instead of leaving school. A friendly Australian postdoc in the Capel lab, Doug Coveney, took Munger under his wing and, with Capel, provided the support and mentorship he had needed to succeed. At the eleventh hour, he had found his place at Duke and his calling in research.

"When Steve first came to my lab, he was about to drop out of basic research, but he made such good brisket that we couldn’t let that talent get away from us!” says Capel. “Building on [JAX Professor] Eva Eicher’s ground-breaking work with testis development, Steve transformed the use of systems genetics to tackle mammalian sex determination. It is such a pleasure to see him thriving at JAX.”

“A moment here, a moment there can make or break you in science,” says Munger. “That was my moment. Working in the Capel lab, I started to love the community and the academic atmosphere. I saw the importance of mentoring, and I liked that component of it as well.”

Steven Munger, Assistant Professor at The Jackson LaboratoryPhoto by Tiffany Laufer

Bar Harbor calling

The research — mapping the genes in mice involved in determining gonadal sexual fate during development — used natural genetic variation in a population of mice to tease apart which genes affect which processes. The complexity of the work required some real computational horsepower, and Munger, who had no computational training, noticed that the most prominent papers being published were from computational biologists. For his postdoc, therefore, he sought out a computational lab, and he focused early on JAX.

“Not long after I started in her lab, Blanche began telling me I should go to JAX after I got my Ph.D.,” says Munger. “And I saw the work [JAX Professor] Gary Churchill, Ph.D., was doing at meetings, which really appealed to me scientifically. So Gary brought me up for a visit on a beautiful day in May and took me to dinner in downtown Bar Harbor. It was my first trip to Maine, and I fell in love with it then and there. After dinner I called Heidi and gushed about my experience. She realized immediately and told her friends that we were moving to Maine.”

Once again, the transition proved to be a massive challenge, one Munger describes as “a year of beating my head against the wall.” He was learning R programming (R is a statistical computing and graphics language common in biomedical research), big data management on computer clusters, rigorous statistical genetics and more. This time, however, he was part of a team from the start, in which he could not just learn but thrive.

“Gary is an excellent mentor, and there was a great group of people in his lab, all of whom helped me get past all the barriers,” says Munger. “And it introduced me to how good interdisciplinary research can be and how it can help answer really difficult questions. It’s like alchemy. We had a physicist, computer scientist, chemical engineer, developmental biologist (me), and of course Gary is a world-leading statistical geneticist, and we brought all our perspectives to bear on challenging systems genetics and data questions. I helped by looking at the data from a biological point of view and spotting the biologically important patterns and differences.”

 Defining the consequences of genetic variation on a proteome-wide scaleMultiplexed mass spectrometry paired with genetically varied mouse population yields broad insights.

That Munger overcame his early postdoc struggles is abundantly clear as he starts his independent research career. Building on the work began in Churchill’s lab (such as detailed in the recent paper in Nature), he is bringing his new computational skillset back to the lab bench. Using a systems genetic approach that combines advanced mouse populations harboring abundant genetic variation with emerging genomics technologies, he’s exploring the complex genetic architecture underlying normal development and disorder. This includes continuing his graduate work defining the genetic underpinnings of primary sex determination, as well as investigating genetic disease, with a current focus on Cornelia de Lange Syndrome (CdLS), a severe, early lethal disease that affects 1 in 10,000 live births. Finally, Munger is following up on his recent study with Churchill to demonstrate that their new understanding of the effects of natural genetic variation on protein expression enables them to create new mouse models with tuned responses in specific cellular pathways.

Munger readily concedes that his career path has been an unusual and meandering one thus far, but he no longer worries about what surprises the future will hold. Quite to the contrary, “I’ve learned to embrace and love the endless supply of unanswered questions that stem from each new discovery, and to follow my curiosity wherever it leads.”