Christina Zimanyi hails from Big Bear Lake, a resort town in the mountains of Southern California, where as a youth she enjoyed just about anything other than the town’s main pastime and tourist attraction: skiing. Between high school and college she spent a year as a Rotary exchange student at a school in Aarau, Switzerland, about 18 miles west of Zurich. With only three weeks of German lessons under her belt, Zimanyi embarked on a courseload heavy in math and science, which she hoped would mitigate her language barrier. She enjoyed her classes so much that year that, when she attended University of California Berkeley the following fall, she veered into chemical biology rather than major in political science as she had anticipated.
At Berkeley, Zimanyi joined Carolyn Bertozzi’s lab her junior year (at the time, she admits, “I had no idea how famous she was”) where she worked with Penny Drake, an immunologist studying the role of the glycan polysialic acid in cell-cell interactions in the immune system. Together they used cell biology techniques and a mouse model to understand how polysialic acid expression on its protein scaffold affected immune cell development.
After a semester abroad in Utrecht, Netherlands, Zimanyi graduated in winter, poised to attend MIT for graduate school the following fall, and finished out the year tutoring high school students in science and math. Although she had some flexibility in determining her doctoral field once admitted, she firmly believed (and still believes) that “a solid foundation in chemistry is important for understanding fundamentals in biology and wanted to make sure I had that solid background to build on when it came to biological questions.”
Once she lighted on chemistry, Zimanyi faced the tough choice between studying general enzymology and “learning multiple techniques, or focusing on one technique and mastering that.” Ultimately, she concluded that, “Crystallography is complicated enough that it’s worth spending an entire PhD starting to learn how to do it.” Zimanyi admittedly adores crystallography and finds structural biology “addicting.” She explains, “I’m a very visual thinker, so the cool thing about crystallography is how tangible the images are.”
In Catherine Drennan’s lab at MIT, Zimanyi collaborated with Professor Joanne Stubbe on ribonucleotide reductase (RNR), the essential enzyme that converts ribonucleotides to deoxyribonucleotides, providing almost all of the cell’s DNA building blocks. E. coli RNR has been studied for over fifty years and remains the prototype for RNR chemistry and regulation, but the mechanisms of its complex allosteric regulation are as yet unresolved. Using X-ray crystallography in combination with other structural techniques, including electron microscopy and small angle X-ray scattering (SAXS), Zimanyi and her peers determined how different oligomeric states of enzyme subunits rearrange to control both enzyme activity and specificity. They obtained the first snapshots of RNR subunits in complex, which allowed them to propose a mechanism for the complex allosteric regulation first observed fifty years ago.
After earning her doctorate, Zimanyi was determined to tackle membrane proteins for her postdoctoral research. Membrane proteins remain “one of the biggest unexplored fields in crystallography…because they’re so difficult.” Both socially and scientifically, the Gaudet lab, which specializes in membrane protein crystallography, was “exactly what I was looking for.” Apparently, the feeling is mutual; Rachelle Gaudet characterizes Zimanyi as “a wonderful asset as a member of my research team. She brings a lot of creative energy to her work and also contributes to the lab by freely sharing her knowledge and ideas with other lab members.” Reciprocally, Zimanyi finds Gaudet’s mentoring style ideal, “a perfect balance of nurturing and still giving postdocs the space they need to develop on their own.”
This spring, Zimanyi earned the Jane Coffin Childs 3-year fellowship for her research on the Transient Receptor Potential Ankyrin 1 (TRPA1), an ion channel expressed in nociceptors that is involved in direct pain sensation. Activated by multiple types of stimuli including noxious electrophilic molecules like allylisothiocynate (AITC, found in wasabi, horseradish, and mustard oil) and acrolein (the molecule that makes burning fat smell acrid), which react with cysteines in the intracellular region of the channel, TRPA1 is responsible for the pain provoked by eating a wad of wasabi or staring too long at an open BBQ. Using structural techniques (including, but not limited to, X-ray crystallography) Zimanyi aims to unravel the details of how noxious chemicals elicit pain through this channel. According to Gaudet, “Christina’s project is exciting because it aims to address important unknowns [such as] how can TRPA1 be responsive to such different noxious stimuli as pungent mustard and noxious temperatures? And how is the presence of stimulus, which seems to be sensed by large intracellular appendages, communicated to the ‘gate’ that opens a pore across the cell membrane?” Hopefully, increased understanding of pain response will contribute to the development of new pain therapies that are safer or more effective than opioids and other addictive pain treatments.
In the meantime, Zimanyi relishes the shift from grad school to postdoc, especially the transition from chemistry to biology: “I really enjoy being in a different department…the way people think about things is slightly different, so I’ve gotten better at thinking big picture. At the end of the day I’m looking at one protein, but I’m better at appreciating the bigger picture of why it matters in a biological context. ”
Although her exploits abroad were not directly related to her research career, past or present, she has come to realize, “My exchange experiences have helped me a lot in science.” Sometimes as a scientist, “you have to be good at being dumb. That’s something I learned well as an exchange student when for two months no one could understand anything I was trying to say.” While those months were deeply humbling they taught her “that just because people don’t understand me or I don’t understand someone doesn’t mean I’m stupid, it just means the communication’s not there yet.” In advanced scientific research, as in an alien environment, “You’re in completely uncharted territory…a world of the unknown.”
With three years of postdoctoral funding to go, Zimanyi has yet to decide whether she will continue charting this territory in the realm of academia or industry. But, whether she teaches in future or not, Zimanyi has already made her mark in the field of education. One of her proudest achievements is a figure in a biochemistry textbook. The latest edition of Lehninger Principles of Biochemistry, the same textbook Zimanyi used in college, features a structure she solved in grad school. “I’m in the textbook!” she declares, “I can retire!” Except, “I’d probably get bored,” she confesses. Despite her extracurricular interests in tap dance and beer connoisseurship (as a self-proclaimed “beer geek”), Zimanyi’s number one hobby remains crystallography and she’ll likely grace the pages of a few more textbooks before launching a second career hoofing at craft breweries around the globe.
Find out more in PubMed