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Biophysicist in Profile

Eva Nogales

Eva Nogales

December 2014 // 7236

“Both of them were obsessed with giving my brother and me a college education,” Eva Nogales recalls, of her parents. Nogales’s mother and father grew up in Spain following that country’s Civil War. Both were unable to go to high school, as they needed to start working when they became teenagers. During Nogales’s own childhood in Spain, her father worked as a truck driver and her mother was a homemaker. Given that circumstance had prevented them from finishing school, they were always concerned about their children getting an education. “Our studies,” Nogales says, “were paramount and although we did not have money for luxury, we always had brand new textbooks and never missed class – I think I attended school several times with a fever!”

As a young woman, Nogales, who is now a Professor of Molecular and Cellular Biology at the University of California, Berkeley, a senior faculty scientist within the Life Sciences Division at the Lawrence Berkeley National Laboratory (LBNL), and a Howard Hughes Medical Investigator, became interested in science after watching Carl Sagan’s Cosmos: A Personal Voyage. “[Sagan] was a fantastic communicator of science that had a gift both for making difficult concepts understandable and for piquing your curiosity,” she explains.

Nogales found a path for her interest in science with the help of her high school physics teacher, who made her realize “the beauty of being able to explain natural laws through math,” Nogales says. Nogales was inspired to study physics at the Autonomous University of Madrid, where she earned her bachelor’s degree. After her undergraduate career, she completed her thesis work at the Synchotron Radiation Source, a national lab in the United Kingdom, studying the assembly of drug-induced tubulin polymers using time-resolved small angle x-ray scattering and cryo-electron microscopy (cryo-EM). In particular, she looked at tubulin polymers assembled in the presence of vinblastine and taxol, two anticancer agents.

Nogales then undertook postdoctoral training with Ken Downing at the Lawrence Berkeley National Laboratory. She says, “Ken is an expert in electron crystallography and was interested in solving the structure of tubulin using an aberrant polymer that forms in the presence of zinc and results in 2D sheets of antiparallel protofilaments. Using a combination of electron diffraction data and images, our lab obtained the first atomic model of tubulin.

As an added bonus, the 2D sheets of tubulin had been stabilized with taxol, an anticancer agent that stops the dynamic behavior of microtubules and freezes cell division. So, we could describe the taxol binding site and postulate its mode of action. It was really hard work, but it REALLY paid off!”

In the Nogales lab, everyone’s ears are sensitized to the rapid, purposeful ‘click-click-click’ of high heels on the floor, which likely means that Eva has entered the lab and is coming to talk to someone.

- Gregory Alushin

After completing her postdoc, Nogales joined the Molecular and Cellular Biology Department at the University of California, Berkeley. Her colleague in the department, Robert Tjian explains, “We decided to hire her in the MCB Department based on her beautiful work on microtubules. […] After Eva joined MCB, I encouraged her to work on a new area of biology – transcriptional regulation.” The two collaborated on the EM structures of the human TFIID complex and human mediator, and Nogales introduced high resolution cryo-EM to Tjian’s lab. The two have had a pleasant and productive working relationship over the years. “She is immensely energetic, passionate about good science, highly focused, visionary, and an absolute pleasure to work with” Tjian says. “She is also, in my opinion, one of the very best single particle reconstruction cryo-EM practitioners in the world. I would pity anyone who thinks they can weaken her resolve.”

Nogales’s lab uses cryo-EM to visualize the structure of microtubules and other cytoskeletal components, like septins, and the machinery involved in gene regulation in eukaryotes, especially during transcription initiation. This field has undergone a revolution in recent years due to new detector technology, which is leading to structures being visualized with unprecedented resolution. As she progresses in her research, she says, “I want to keep building complexity into the systems I study. As a structural biologist, I am a reductionist by nature, but I want to be able to push the limits of the possible to gain biological insight that comes by placing the pieces of the puzzle together and seeing how they can organize, combine, move.”

More than any other aspect of her work, sharing the process and discoveries with her students invigorates Nogales. She explains, “Their brilliance and breadth of understanding, across physical and biological disciplines, is quite amazing. They do keep me on my toes. I love working with them deciphering molecular mechanism puzzles!”Nogales with her family

One of her former PhD students, Gregory Alushin, describes this same passion, “Eva is extremely energetic, incredibly wide-ranging in her interests and insights, and firm in her opinions, positive and negative, which she expresses directly and forcefully. She is an extraordinarily passionate person, first and foremost about science, but really about everything. This is crystallized in her trademark exclamation, ‘It’s un-be-LIEVE-able!’ which can refer to a dazzling new result, the latest book of film to capture her interest, and any other fascinating or exasperating aspect of life.”

Nogales enjoys attending the Biophysical Society Annual Meeting, in large part because of how many speakers are selected from abstract submissions. “It gives young people the opportunity to present to a large audience and get very good projection, [and] now for me is an opportunity to catch talent as it emerges!” she says, “I was given the opportunity to talk at a number of Biophysical Society meetings very early in my career as a postdoc and a junior faculty [member] and it really had an effect of promoting me and my work.”

Outside of the lab, Nogales spends her time with her husband, Howard Padmore, a physicist at LBNL, and their two sons, Daniel and Ricky. “I also like having the opportunity to dance and be loud,” she notes. If she weren’t a biophysicist, Nogales says she would love to be a pop singer, “but I am tone deaf.” Regardless of the fact that she does not perform as a musician, she certainly commands attention. “In the Nogales lab, everyone’s ears are sensitized to the rapid, purposeful ‘click-click-click’ of high heels on the floor, which likely means that Eva has entered the lab and is coming to talk to someone.” Alushin jokes, “It is quite amusing to watch the Pavlovian response of every head whipping around from the computers whenever someone wearing heels walks in. She has trained us all well.”