by Lipi Thukral
“I grew up on a farm in a tiny village where school was considered something not unimportant, but picking apples during harvest time had even higher priority,” says Frauke Graeter, professor at University of Heidelberg, and Heidelberg Institute of Theoretical Studies, Germany. She loved math at school, but in the very rural region where she grew up in the 1980s, math as a profession was nothing she could imagine. She also loved natural science subjects, and because there was a small chemical company nearby, chemistry did not appear as odd a subject to study. She was also intrigued by biology, and as a result took botany and zoology classes on the side. Graeter admired many of her teachers and at that time wanted to become a school teacher.
During undergraduate studies she attended a lecture on computational biophysics by Jeremy Smith at Heidelberg University, and suddenly knew that she wanted to become a researcher in that field. Connecting the dots back, she believes that her chemistry (and biochemistry) teacher at high school — one of few scientists with a PhD degree who Graeter interacted with — also inspired her, and might be the reason why she changed her mind from becoming a teacher to becoming a scientist. Luckily, in her career as a scientist, she also has the opportunity to teach and mentor her students.
The path Graeter followed after her undergraduate studies was both difficult and unusual. She knew exactly where she wanted to conduct her PhD research and what she wanted to study – biomolecular simulations in China. “The least obvious thing to do was to go to China for PhD studies back in 2002, when science in China was by far less developed and internationally recognized,” she shares. She was told that following this path would ruin her career, however, this did not deter her from accomplishing what she had set her eyes on. “My advice is to not always listen to your mentors,” she says.
Hualiang Jiang, Shanghai Institute of Materia Medica, was her adviser in China, and Helmut Grubmueller located at Max Planck Institute of Biophysical Chemistry, Goettingen, co-guided her PhD studies. Graeter leveraged molecular dynamics tools to provide a comprehensive picture of mechanical stability of proteins that undergo force-induced conformational transitions. Titin, a kinase and filament of muscle cell, was one of the proteins under her lens. She began to solve the mystery of how kinase activation is triggered upon muscle stretch and realigns after the stress release. She found that the mechanical strain on titin domain leads to a sequence of conformational changes that result in an open conformation of the catalytic cleft leaving the catalytic core intact. Along with this work, she also investigated pheromone binding protein and florescent protein asFP595 to shed light on their molecular properties and how their structures guide the function in context of mechanism and kinetics.
Graeter went on to conduct her postdoctoral research at Columbia University, where she worked on a joint project of the laboratories of B.J. Berne, Chemistry department, and Julio Fernandez, Biology department. The goal of her postdoc studies was to elucidate the molecular mechanism of protein dynamics under force, during processes such as protein folding and unfolding of enzyme catalysis. At 30, Graeter began her first faculty job. She joined as an independent Junior Group leader at MPG-CAS Partner Institute for Computational Biology, Shanghai. During her second stint in China, Graeter learned to speak fluent Mandarin.
“My husband and I were used to living in different continents throughout large parts of my undergraduate, graduate, and postdoc times,” Graeter said. On the other hand, they always agreed that they wanted to have a not-so-small family. She got the offer for a permanent group leader position from HITS in Heidelberg right around the time of the birth of her first son, allowing her to move back from Shanghai to where her husband was living. Her professorship at Heidelberg University began in 2014, which coincided with the birth of her third son.
Currently, her research focuses on understanding physical principles of how atoms interact with one another to explain a tiny bit of the complexity of life. The questions connected to her research are all around - How does our body realize that we run, jump and feel all that gravity? Tiny little building blocks, our proteins, make and feel those forces, and Graeter studies, with computer simulations, how this works. “This is so important, because nothing in life, from making bone to stopping bleeding, would work without such forces,” she further explains.
Her latest interdisciplinary work in collaboration with Edward Lemke is published in Cell 2016 with her postdoctoral colleague Davide Mercadante. The study highlights the origin and underlying principles of fast yet specific protein trafficking. In particular, they showed that rapid fluctuating of the intrinsically disordered protein FG-Nups populates an ensemble of structures that are predisposed to specific binding with nuclear transport receptors.
Mercadante considers Graeter to be the best boss ever. “The main quality that jumps out is her humanity in working relationships and her respectful attitude towards someone else’s thoughts, ideas, and scientific hypotheses,” he says. “She is a keen listener to any crazy hypothesis that anybody else would probably immediately discard and is ready to plastically adapt her thoughts in order to expand her scientific scope.” According to Mercadante, “This is her main strength in science: she teaches and learns at the same time, all the time.”
According to Graeter herself, working with young scientists and students is the most rewarding aspect of her work. She says, “[My lab] is like my second family, and I like growing further along with them.”
Her own greatest role model is her mother who encouraged her and showed that it is up to you what you achieve. Her scientific mentors include her former adviser Helmut Grubmueller, who taught her about biophysics and how to do good science; Bruce Berne, with his curiosity, sharp mind, and ability to ask simple questions; and lastly, the late Klaus Schulten, who during all his life was so enthusiastic about Molecular Dynamics simulations and their impact on biological discoveries.
Her scientific life is exemplary for young scientists. She advises to solve the problems they you’re excited about, and to focus on the research itself, without being too distracted by all the other obligations and expectations. She also urges women not to hesitate to have children – even several, if they wish – while running a lab.