TCBG Seminar

Zooming in on Single Molecules: Studying Protein-Nucleic Acid Interactions at the Single-Molecule Level

Professor Xiaowei Zhuang
Department of Chemistry and Chemical Biology
Harvard University
Cambridge, MA

Wednesday, December 5, 2007
4:00 pm (CT)
112 Chem Annex


Biological processes often involve complex dynamics. Monitor the behavior of individual molecules and molecular complexes in real-time allows their dynamics to be directly observed, greatly facilitating mechanistic understanding of these complex processes. Toward this overarching goal, our research program has three major thrusts: (1) to understand how biomolecules function, especially how proteins and nucleic acids interact, using single-molecule approaches; (2) to develop live-cell imaging and singleparticle tracking techniques and to investigate virus-cell interactions using these techniques; (3) to develop super-resolution optical imaging methods that allow cells and tissues to be imaged at the molecular-scale resolution. In this seminar, I will primary focus on the first area and talk about our recent single molecule-studies of two medically important reverse transcriptase (RT) systems, telomerase and HIV RT. Telomerase is a specialized RT that uses the sequence encoded in its own RNA component as a template to synthesize DNA telomere and maintain chromosome stability. The HIV RT is a viral protein that converts the singlestranded RNA genome of HIV into double-stranded DNA for host-cell integration. Using single-molecule approaches, we have investigated the assembly pathway, structural dynamics and structure-function relation of both systems and discovered novel assembly and structural dynamics that are critical for their enzymatic functions. If time allows, I will also briefly touch upon the third area and introduce the super-resolution optical imaging method that we have developed.

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