Biophysical Society Bulletin | March 2018

Biophysicist in Profile

Angela Gronenborn Area of Research Structural Biology

Institution University of Pittsburgh Medical Center

At-a-Glance

Angela Gronenborn , University of Pittsburgh Medical Center Rosalind Franklin Chair and Distin- guished Professor in the Department of Structural Biology at the University of Pittsburgh School of Medicine, grew up in Germany with a dream to become a mathematician, “just playing with numbers.” As a teenager, she was advised against pursuing this career due to the limited op- portunities available to women, and instead undertook studies in chemistry and physics. Early in her career, she determined that she would use NMR to solve protein-DNA complex struc- tures —which was impossible at the time. “But,” she says, “in the end I did it.” This February at the 62 nd Annual Meeting, Gronenborn assumed the position of Biophysical Society President for 2018–2019.

Angela Gronenborn

Biophysical Society President Angela Gronenborn has loved mathematics for as long as should can remember. She excelled at the subject, beginning in her early years. At her primary school in Cologne, Germany, she was so much farther along than her classmates that she often was excused from class. “During math lessons, I frequently was allowed to go shopping for my teacher — I know, these were different times and a different place,” she says. Gronenborn attended an all-girls boarding school for high school. She continued to love math, and discovered physics and chemistry, which became new favorite subjects. As she approached graduation and began to think more seriously about her future, she naturally gravitated toward further study of mathematics. “Both the high school principal and my father told me that this was a bad idea,” she says. “One may wonder why — the reason both gave me was that since I didn’t want to teach, it would be impossible for me to earn a living as a mathematician because I was a woman.” Because the option of a career in mathematics was eliminat- ed, she decided to pursue physics and chemistry. She gradu- ated from the University of Cologne in 1972, and then contin- ued on to earn her master’s degree in chemistry in 1975. She undertook PhD studies in chemistry at the same institution. “My PhD thesis work centered on 13C NMR spectroscopy of aromatic N-oxides and related compounds,” she explains, “comparing experimentally determined coupling constants with quantum mechanical calculated ones.” While carrying out her thesis research, Gronenborn moon- lighted at the genetics institute where her brother Bruno worked as a plant molecular biologist. “He is sort of indirectly responsible for what I do today,” she shares. “It was the time of the molecular biology revolution —DNA sequencing hadn’t

been invented yet — and there was this amazing group of people I spent time with, work and otherwise. That’s when I decided that I wanted to use NMR to solve protein-DNA complex structures, which was totally impossible at that time. But in the end I did it.” Following her PhD, she undertook a postdoctoral position at the National Institute for Medical Research (NIMR), Med- ical Research Council, in Mill Hill, London. “The fellowship application I wrote was on using NMR to solve structures of protein-DNA complexes — impossible at the time, since none of the heteronuclear, multidimensional methods had been invented yet,” Gronenborn explains. “Miraculously, I was awarded my fellowship. In reality, I worked on L. casei dihy- rofolate reductase (DHFR) using nuclear magnetic resonance (NMR). And because I loved “shimming” (only NMR people would know what that means), I managed to get my first Nature paper, reporting on the direct observation by NMR of two coexisting conformations the DHFR-trimethoprim-NA- DP+ complex.” An earlier paper holds a more sentimental meaning for her, however. “In my mind, the most important first mentioning of my name in scientific print is in my brother’s 1978 Nature paper,” she shares, “where in a figure legend he thanks me for providing N-methyl-N-nitrosourea, which was easy for me to synthesize, and allowed him and Jo Messing to create a unique EcoR1 site in M13 — the beginnings of using M13 for cloning.” After her postdoc, she stayed on at NIMR as a member of the scientific staff in the division of molecular pharmacology and physical biochemistry. In 1984, she took a position as head of the biological NMR group at the Max Planck Institute for Biochemistry in Munich. Four years later she relocated her

March 2018

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