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Biophysicist in Profile

Silvia Cavagnero

Silvia Cavagnero

December 2015 // 4593

Silvia Cavagnero, University of Wisconsin-Madison, grew up in Lido di Ostia, Italy, a village by the seashore near Rome. Cavagnero loved reading as a child. “I really enjoyed reading everything: street signs, magazines, comics, the newspaper, novels, even entire random pages of the encyclopedia,” she recalls. She thought that she would pursue a career as a school teacher or a writer, but became interested in a career in science as she read more science-related pages in the encyclopedia. She began reading biographies of famous physicists and biologists like Albert Einstein, Enrico Fermi, Ettore Majorana, James Watson and Francis Crick, Dorothy Hodgkin, Marie Curie, and Rita Levi Montalcini. She fortunately also had inspiring high school science teach­ers, who always encouraged her inquisitiveness. “I gradually realized how powerful and rewarding it can be to really understand why and how things happen in the world right around us,” she says, “and how thrilling it is to discover new things that have never been seen before.”

She decided to study chemistry as an undergraduate student at La Sapienza University of Rome, and found the subject was a good fit. “I fell in love with the subject, which seemed to explain so much about our everyday world… Though my favorite subject was biology, it was only through chemistry that I could really understand some of what was going on in my biology classes.”

Cavagnero moved to the United States and earned her master’s degree in chemistry at the University of Arizona, Tucson. She then went on to pursue her PhD at Caltech in the lab of Sunney I. Chan. “I kept being drawn to big unsolved problems in biology and to the idea of gaining a fundamental understanding. I learned more math and physics and discovered how useful they can be as tools to understand biology in a more quantitative way,” she says. “I suppose that this really is what biophysics is all about!”

“I gradually realized how powerful and rewarding it can be to really understand why and how things happen in the world right around us.”

In Chan’s lab, Cavagnero worked on the origins of the exceptional thermal stability of rubredoxin, a protein from the hyperthermophilic bacte­rium Pyrococcus furiosus, which lives in boiling water. As a graduate student, she became interested in protein folding. Though she did not work in the protein folding field at that time, she did pick up some important biophys­ics basics that would prove useful later on: the fundamental principles of kinetics, thermodynamics, quantum mechanics, and how to make and purify proteins. That knowledge became important during her postdoctoral work at Scripps Research Institute in the lab of Peter Wright. “In my postdoctoral research, which was carried out in collaboration with Jane Dyson, I studied the folding kinetics of apomyoglobin at atomic resolution by NMR [nuclear magnetic resonance] spectroscopy,” she says. “When time came to apply for an independent academic position, I was ready to bring protein folding and biophysics to more cell-relevant environments. I was driven by a compelling need to explore how proteins fold, misfold, and aggregate under conditions where all the relevant states (unfolded, folded, and intermediates) are actually populated in the living cell. I also realized the importance of taking into account key cellular players such as the ribosome and molecular chap­erones to understand how proteins fold and how they manage to bypass aggregation in the cell.”

Following her postdoc, Cavagnero accepted a posi­tion as an assistant professor in the Department of Chemistry at the University of Wisconsin- Madison, where she still works to this day, though now as a full professor. Currently, she works on the mechanism of protein folding in the cellular environment, and on the role of the ribosome and other cellular components, especially the Hsp70 chaperone, in protein folding. “In my work, I make extensive use of biochemistry, molecular biology, time-resolved fluorescence spectroscopy, and multidimensional NMR,” Cavagnero says. “I also work on improving the sensitivity of NMR spectroscopy by laser-driven approaches, primarily photochemically induced dynamic nuclear polar­ization (photo-CIDNP). The hope is that we will soon be able to use a much more sensitive version of NMR spectroscopy to solve biological problems at atomic resolution and sub-micromolar concen­tration.”Cavagnero with her daughters, Cecilia and Irene, and dog Daisy.

One of the greatest challenges in Cavagnero’s career, and something that has been rewarding for her, is serving as a mentor to her students. “There is really no training in [mentoring] provided to postdocs, and this is especially unfortunate,” she elaborates. “I have faced this challenge by trial and error, and by learning to talk to my students more – not just about science, but also about their daily needs, their hobbies, as well as their future aspira­tions.” Nurturing her students and helping them accomplish their personal and professional goals is one of the most enjoyable aspects of her work. “I take the greatest pride in seeing my undergraduate and graduate students and postdocs grow in both their intellectual skills and self-confidence, while in my lab,” she explains.

Martin Gruebele, University of Illinois, works with Cavagnero in the leadership of the Biophysi­cal Society’s Biopolymers in vivo Subgroup. He shares, “Silvia is a wonderful person, who cares a lot about students and others doing science, and from that [it] automatically follows that she loves science and discovery."

Cavagnero also works to support people from underrepresented groups working in science. She has served on the Society’s Committee for Inclu­sion and Diversity, and has had the opportunity to speak at the Society’s Summer Research Program in Biophysics. “Giving lectures about my research at the Summer Research Program in North Carolina has created unprecedented opportunities to make a small difference in the life and emerg­ing careers of young biophysicists with different ethnic backgrounds,” she explains. Her friend Marina Ramirez-Alvarado, professor of biochem­istry and molecular biology at the Mayo Clinic, shares this enthusiasm, and the two connected over this and have worked together organizing a US/Mexico Workshop in Biological Chemistry in the past. “Silvia is a hard worker and gentle leader who accomplishes an incredible amount of work without making a lot of noise,” Ramirez-Alvarado says. “I am sometimes very loud and there is a value of doing things quietly. Silvia is very modest but she is a force of nature.”

When Cavagnero is not in the lab, she spends time with her husband and two daughters. Though managing both work and family life can be dif­ficult at times, Cavagnero, like others, has worked to find balance. “I have learned to uncondition­ally choose family without ever looking behind,” Cavagnero says. “In a way, it is really comfort­ing to know that proteins will keep folding and unfolding in the cell no matter what. Proteins will always let you unveil their mysteries when you are ready to interrogate them.”