And, while Miller did secure a position at Brandeis, two years later the “two-body problem” became an issue again. After many unsuccessful attempts at finding a suitable destination with her husband, Miller eventually received a job offer she simply could not refuse: assistant professor in the Johns Hopkins University chemistry department.
Although her long-distance “e-marriage” was trying, Miller had a fantastic time at Hopkins. “I had a chance to launch some very exciting studies and to work with fabulous colleagues; I would have loved to have been able to stay permanently.” Despite the best efforts by her colleagues, the university couldn’t find a way to open up a spot in the physics department for her husband. “After eight years, our family had reached a point where our first child was ready to start school, and we just had to be in the same city.”
That led Miller to a difficult professional decision— relocating her lab to the University of Kentucky in 1999 so her family could be together.
Heading into Orbit
While the nature of the projects in Miller’s group at the University of Kentucky varies to exploit the composition and interests of her lab members, she maintains an overall theme of combining principles of biophysics and spectroscopy to examine protein control over cofactor reactivity.
The lab focuses on two enzyme types: superoxide dismutases and enzymes that use flavins as cofactors. Superoxide dismutases, which metabolize toxic superoxide ions (O2-), regulate the reactivity of potentially reactive chemical species and are fairly well studied, providing a firm foundation for detailed studies of fundamental questions.
“That is not to say superoxide dismutase has no more new stories to tell, because it certainly has,” Miller says, noting some exciting work in which her lab provided the first mechanistic explanation as to why iron- or manganese-containing superoxide dismutases become inactive if their cofactor is exchanged with the opposing ion, even though the three-dimensional structures of the two enzyme types are basically superimposable.
Out of Focus: Language Barrier
While you won’t catch more than a hint of a Canadian accent in speaking with Miller these days, she admits to having had occasional communication “challenges” when she first moved from Guelph to New Haven, Conn. This led to one of her more bizarre graduate school experiences. One day, while returning from school, she was approached and accosted by a pair of youths who demanded her bicycle. “Their accent was so strong and foreign to me that I could barely understand them,” she says. Add in the fact that she came from a small, quiet college town, and she was not prepared for such a situation. “So rather than run away immediately (and lose my bike), I responded with a polite, if scared, refusal. Then they had trouble comprehending me. After several back-and-forth exchanges in which I can remember thinking I was completely crazy to be insisting on retaining my bicycle and repeating ‘I beg your pardon’ (because I still could not understand their English), instead of fleeing back up the street, one of them cracked a smile.” She says, “This whole conversation was probably the last thing they expected and in retrospect, it really was humorous. Once it had become a joke, they waved me on and I rode off. I would, nonetheless, not recommend this as a general strategy.”
Other recent spectroscopic analysis has revealed insights into how superoxide dismutase controls the movement of the electrons between the active site metal ion and substrate. “Proteins do not have good means of controlling electrons directly,” Miller says. “But we found that the big bridge by which superoxide dismutases regulate the sources and destinations of the transferred electrons is the protein’s exceptional control over protons, because the protons have a very big influence over where the electrons go.”