Four years ago, Nicolas Buchler was strictly a theorist. He never really felt the need to prod bacteria or yeast until he developed an idea about how genes might turn on and off. And then, rather than waiting for someone else to do the experiments, he decided he had better test the ideas himself.
Now, Buchler (BUSH-LER) is building a lab at Duke to continue developing his theories and to perform the hands-on experiments to test them.
His research explores the principles of the physics and biology happening within the cell. It's an interdisciplinary approach to biology that led him to become Duke's first jointly appointed junior faculty member in biology and physics. He also has an affiliated role in the university's Center for Systems Biology at the Institute for Genome Sciences & Policy.
Buchler was captivated by the ways atoms and molecules interacted to make new and different compounds in high school chemistry. As he "engaged science further" as an undergraduate at the University of California, San Diego, he began to appreciate how those basic atoms and molecules came together to create the building blocks of life, such as DNA, RNA and the proteins that control the body.
"Understanding these basic components of life made me want to further explore how biology, chemistry and physics met at a molecular interface within cells," Buchler said. He first chose to focus on physics then directed his studies more toward biology and theory as a doctoral student at the University of Michigan in Ann Arbor.
Four years ago, Buchler started theoretical work on how protein sequestration, which occurs when an inhibitor protein binds and inactivates another protein, creates a sharp tipping point, or threshold, at which genes switch from completely off to all on. This mechanism is common in regulating natural gene networks.
Because it was a relatively new theoretical work, Buchler decided he wanted to test it himself. He moved to New York's Rockefeller University as a post-doc and worked under yeast research specialist Fred Cross and took a short course in experimental research at Cold Spring Harbor in New York to learn yeast genetics.
He and his colleagues went on to build an artificial gene network in yeast to test whether protein sequestration could generate all-or-nothing responses in gene expression. The agreement between theory and experiment "was remarkable," and showed that protein interactions could transform how and when genes expressed themselves.
"Nick's theoretical background in physics really put him at the forefront of quantitative biology," said Dan Gauthier, chair of Duke's physics department.
Last fall, Buchler was tapped to become an assistant professor at Duke and set up both theoretical and experimental labs to continue exploring how protein sequestration affects circadian rhythms and whether there is a certain threshold at which genes turn on in natural systems.
He has also stepped up to teach a new introductory course called "Gateway to Biology through Molecular Biology." The course is part of the biology department's effort to further challenge freshmen and introductory biology students to think of biology a "little less horizontally and more vertically," said Dan Kiehart, the chair of the biology department. Buchler's quantitative and molecular approach to biology makes him ideal as one of the leaders in this initiative, he said.
With both strong quantitative and experimental skills, Buchler is also an integral new player in the "growing cadre of young faculty" in systems biology, said Philip Benfey, director of the IGSP's Center for Systems Biology. He will also contribute to the biophysics major developing within the physics department.
Buchler lives in Chapel Hill with his wife and 4-year-old daughter. When not studying yeast genes or thinking about them, he enjoys exploring the "fascinatingly different" types of 100-foot trees in the Duke Forest with his family.