Angela M. Gronenborn, University of Pittsburgh Medical Center Rosalind Franklin Chair and Distinguished 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 opportunities 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 structures — which was impossible at the time. “But,” she says, “in the end I did it.” This February at the 62nd Annual Meeting, Gronenborn assumed the position of Biophysical Society President for 2018–2019.
Biophysical Society President Angela M. 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 eliminated, she decided to pursue physics and chemistry. She graduated from the University of Cologne in 1972, and then continued 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 moonlighted 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), Medical 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 dihyrofolate 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-NADP+ 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 group to the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, where she served as chief of the structural biology section.
Gronenborn is currently the University of Pittsburgh Medical Center’s Rosalind Franklin Chair and Distinguished Professor in the Department of Structural Biology. Her research presently focuses on three main areas in biology: HIV pathogenesis, protein-carbohydrate recognition, and protein deposition diseases; she uses physico-chemical approaches in her work.
Her group has developed new NMR methods for determining three-dimensional structures of biological macromolecules and applies these to challenging systems. Key contributions include the development of restrained molecular dynamics and simulated annealing algorithms and multidimensional, heteronuclear spectroscopy, which allowed the extension of conventional NMR methods to higher molecular weight systems. The Gronenborn group has solved solution structures of a large number of medically and biologically important proteins, including cytokines and chemokines, transcription factors and their complexes, and various HIV- and AIDS-related proteins.
You need to be passionate about what you do; if you are passionate, you will be good at it, because this will be your constant companion.
- Gronenborn
Her biggest challenge at this career stage is staying on top of developments in the field. “Right now, [the challenge] is to keep abreast of all the new discoveries and cutting-edge methods in science,” she shares. “I don’t want to just continue with my well-established approaches.”
Gronenborn finds great fulfillment in her research, viewing it not only as her career but also her primary leisure pursuit. “I get paid for doing my hobby, so there is not much time for other pastimes,” she says. “I love the arts, however, and visit museums, concerts, and plays. Having a few spare hours in any city in the world, I’d find a museum and go to a modern art exhibit.”
The most rewarding aspect of her work comes from discovery, whether hers personally or that of her trainees: “When for the first time one sees a new structure, or finds an explanation for a puzzling observation,” she shares. “Equally, when I see how a spark ignites in a student and she or he experiences the thrill of science.”
Perhaps because of this thrill of discovery, she says that she would love to revisit an earlier period of her career. “My dream for my career-end is to work another time as a postdoc,” she says, and “have all the fun again that made this period of my career the most enjoyable.”
At the 62nd Biophysical Society Annual Meeting in San Francisco, California, this February, Gronenborn assumed the position of Society President. In this position, she hopes to emphasize scientific excellence and promote the importance of basic research at the interface of physics, chemistry, and biology. Like many members, she values the Society for the opportunities made available to students and biophysicists early in their careers. “The Biophysical Society — and its Annual Meeting — allow students and postdocs to present their work in a very large setting,” she says. “Several of my graduate students gave their first talks at the Biophysical Society Annual Meeting. This is a terrific opportunity for young people.”
For young scientists, whether in biophysics or another discipline, Gronenborn has one important piece of advice: “You need to be passionate about what you do; if you are passionate, you will be good at it, because this will be your constant companion.”