Biochemistry, Systems Biology
Dr. O'Shea is also Paul C. Mangelsdorf Professor of Molecular and Cellular Biology, and a professor of chemistry and chemical biology. She was appointed as an HHMI investigator in 2000; in 2013 she became Vice President and Chief Scientific Officer of HHMI; in September 2016, she assumed the role of HHMI President.
Circadian Clocks and Transcriptional Control
The most impressive clocks can’t be found on a phone, wristband, or wall. These timepieces are hidden inside cells, where they tick along naturally recurring (circadian) rhythms, alerting the cell when it’s time to express various genes. Erin O’Shea’s research has examined the circadian clock found in blue-green algae, or cyanobacteria.
O’Shea and colleagues have shown how a master transcription factor, RpaA, triggers an entire cascade of circadian gene expression by regulating a set of transcription factors known as sigma factors. The genes controlled by RpaA and the sigma factors help the bacterial cell sustainably generate the energy compound ATP by regularly shifting its metabolism between daytime photosynthesis and nighttime use of stored carbon sources, such as glycogen.
In other work, O’Shea and collaborators have analyzed how cells make the most of a limited number of transcription factor proteins, through their dynamics. You can interpret your friend’s words in different ways, by listening to her delivery. Similarly, O’Shea’s team has shown, the control regions of genes can interpret a transcription factor’s signal based on its communication style – steady, pulsing, shorter or longer, etc. Decoding these dynamics, the DNA identifies the signal and activates the correct gene(s).
As a scientist and leader, Erin O’Shea is known for being direct and focused. Her style was evident early on. As a beginning biochemistry graduate student at MIT in 1988, O’Shea read a prominent paper in Science and set out to test the proposed protein structure, ultimately correcting it. Her efforts advanced understanding of the leucine zipper, a key part of many transcription factors that guide cells to turn genes on or off. She was rewarded with a rare faculty position straight out of graduate school, at the University of California, San Francisco.
Since then, O’Shea has consistently contributed to our understanding of a cell’s fundamental ability to survive, and succeed, based on how it senses and responds to environmental changes. At Harvard University since 2005, her research lab has revealed key mechanics behind the circadian clock and transcription factor dynamics. O’Shea and colleagues have contributed new knowledge and refined analysis at different scales, including protein structures, gene regulatory networks, and the applied mathematics of biochemical interactions.
O’Shea was named an HHMI investigator in 2000 and elected to the National Academy of Sciences in 2004. Her leadership extends well beyond the lab bench. Beginning September 2016, O’Shea will become HHMI’s sixth president, a position she assumes after serving as the institute’s chief scientific officer since 2013. During her tenure at HHMI, she has emphasized that the best science often emerges when skilled researchers are given the flexibility and freedom to work on whatever problems strike their curiosity. In the years to come, she says, she seeks to ensure that HHMI is giving that opportunity to an increasingly inclusive community of excellent scientists, who represent a rich range of cognitive and cultural diversity.
As part of her transition to the role of HHMI president, O’Shea is winding down her Harvard lab and will be developing a research program at HHMI’s Janelia Research Campus.