Across the Border
|Overlay of heteronuclear single-quantum coherence spectra of uniformly 15N-labeled nitroreductase, collected at 37° C (red) and 4° C (black) showing a striking loss of dispersion attributable to conformational averaging.
Such a sense of wonder about the natural world has been a staple of Miller’s mindset since her youth in Toronto. She recalls that her scientific awakening occurred around the time she was 13 years old, when her family took her and a friend for a weekend naturalist program on Ontario’s Bruce Peninsula. During their hikes, Miller was fascinated by how much information the guides knew about every moss, plant and liverwort they passed, including tidbits such as the plant’s habitat range, what chemicals were inside it and how the indigenous people used it.
“I remember one foggy morning walk in particular,” she says. “We had heard a squawk in the distance above us, and one of our guides immediately told us that was a goshawk. That weekend revealed for me just how much information surrounds us, but we don’t notice, and so it passes us by. And I keep thinking how much richer our whole experience could be if we paid attention more.”
That weekend getaway eventually led to a vigorous pursuit of science projects, both for science fairs and personal curiosity; Miller even dabbled in some plant breeding, which led her to pursue a degree in molecular genetics at the University of Guelph in Ontario, Canada.
Along the way, Miller also began taking physics courses, because she found that most of the biology courses were too descriptive and she was eager to understand science at a deeper level; in fact, by the time she graduated in 1982, Miller was just one course short of a physics major.
At Guelph, Miller also got her first taste of NMR and EPR spectroscopy. “The notion that we could observe signals from single atoms or electrons was just amazing,” she says, “and it was a technology I wanted to learn more about.”
To do that, Miller crossed the border into the United States, following a career trajectory that included graduate studies at Yale University with Gary Brudvig, analyzing the assembly and mechanism of photosystem II, a postdoctoral position with William Orme-Johnson at the Massachusetts Institute of Technology and a second postdoctoral fellowship with Al Redfield at Brandeis University, conducting NMR studies on the conformation changes in the p21-Ras protein that contribute to tumor development. Her first independent appointment was at the Johns Hopkins University in 1992.
Her professional journey was far from a series of seamless transitions. For example, Miller considers her time in graduate school to have been quite rewarding but not entirely successful. “I had two projects that either didn’t prove interesting to anyone other than me, or, by the time they worked, someone else had published the result,” she admits, adding that she learned valuable lessons about what constitutes good science, and that helped her career immensely later on. “I am enormously grateful to Gary Brudvig for giving me independence so I could learn these important lessons before it was my career on the line. This was especially courageous of him considering that, at the time, his was.”
|2D PASS solid-state 15-NMR spectrum (bottom) and cross-polarization magic angle spinning 15N solid-state NMR spectrum of tetracetyl riboflavin labeled with 15N at positions N1, N3 and N5. For details, see Koder et al. 2006.
Other events were unforeseen, however, such as Miller having to leave her first postdoctoral position at MIT because her lab ran out of funding, forcing her to scramble to find a new lab to work in. This situation was made more difficult by the facts that her husband had just gotten a job in the Boston area and that Miller wasn’t a U.S. citizen and would have to leave the country if she didn’t find a U.S. Immigration and Naturalization Service-acceptable position very quickly.