Visualizing the Bacterial Transcription Cycle in Action
Event Details
- Type
- Monday Lecture Series
- Speaker(s)
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Seth Darst, Ph.D., Jack Fishman Professor and head, Laboratory of Molecular Biophysics, The Rockefeller University
- Speaker bio(s)
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Transcription is the major control point of gene expression and RNA polymerase (RNAP), conserved from bacteria to humans, is the central enzyme of transcription. Our goal is to understand the mechanisms of transcription and its regulation, focusing on well-characterized Escherichia coli RNAP. The basic elements of the transcription cycle, initiation, elongation, and termination, were elucidated through study of prokaryotes, but a comprehensive structural and functional understanding of the cycle, needed to explain the fundamental control of gene expression and to target RNAP with antibiotics, is lacking. Intermediates in the cycle are transient and heterogeneous, posing challenging for structural biology. Advances in cryo-electron microscopy (cryo-EM) allow visualization of actively functioning complexes under near-native conditions. ATPases remodel transcription complexes, regulating the cycle and coordinating with other cellular processes. We assemble ATPase regulatory complexes with ATP and use cryo-EM to 'watch' the ATPases perform their ATP-dependent functions. To investigate transcription-coupled repair, we examine the Swi/Snf ATPase Mfd as it engages a stalled RNAP elongation complex to release the incomplete transcript, collapse the transcription bubble, and recruit repair machinery. We are also studying how a AAA+ ATPase activates transcription by remodeling the sNholoenzyme to allow promoter melting.
Seth Darst obtained a B.S. from the University of Colorado, Boulder, and a Ph.D. from Stanford University, both in chemical engineering. It took that long for him to figure out that he preferred science over engineering, so he did postdoctoral work with Roger Kornberg at Stanford. There, he learned structural biology and became obsessed with the process of transcription. He joined The Rockefeller University to run a research laboratory focusing on the bacterial transcription cycle. He is currently the Jack Fishman Professor of Molecular Biophysics. He is an elected as a member of the National Academy of Sciences. In addition to the E. coli transcription cycle, he is happy to be working with Professors Elizabeth Campbell and Charlie Rice on structural mechanisms of RNA synthesis in coronaviruses and hepatitis B virus.
- Open to
- Campus Only