Abstract: Series 106, Lecture 2
The Harvey Lectures Series 106 (2010—2011)
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Lecture #2: Thursday, November 18, 2010 — Time and Location
The Biophysics of Gene Regulation, Studied One Molecule at a Time
Steven M Block, PhD
SW Ascherman Professor of Sciences
Departments of Biology and Applied Physics
Senior Fellow, Spogli Institute for International Studies
Stanford University
Stanford, California
Recent advances have led to the new field of single molecule biophysics. Prominent among the enabling technologies is the laser-based optical trap, or ‘optical tweezers’. Ultrasensitive systems for measuring force and displacement based on optical traps permit the nanomechanical properties of individual macromolecules to be explored with unprecedented precision, revealing rich behaviors that were heretofore obscured by ensemble-based approaches. This talk will focus on some of our current work with single-molecule systems, including transcription by RNA polymerase and structural transitions in nucleic acids. We developed high-resolution instrumentation that has broken the nanometer barrier and is thereby able to detect displacements right down to the atomic level, in aqueous buffer at room temperature. Consequently, we can monitor the motions of single RNA polymerase molecules in real time as these step from base to base along DNA. On the practical side, base-pair resolution makes it possible to sequence DNA in a novel way, based on enzyme motions, and points to new directions in nanoscience. The improved stability afforded by the current generation of apparatus has allowed us to reconstruct the energy landscapes for folding transitions in simple nucleic-acid hairpins. Recently, we’ve turned our attention to the regulatory problem of co-transcriptional folding, observing the formation of aptamers and riboswitches in nascent mRNAs, and to the DNA or RNA sequence elements that influence gene expression.