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Xiaowei Zhuang, Ph.D.
Just as a chorus obscures the sound of a single voice—and prevents a listener from discerning how an individual singer interprets a piece of music—the collective behavior of a mass of molecules obscures a precise understanding of how a single molecule behaves in a dynamic biological process. Yet while a singer can step forward for a solo, identifying the “voice” of a single molecule is not so trivial.
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Xiaowei Zhuang, Ph.D.
Assistant Professor of Chemistry and Chemical Biology, and of Physics
Harvard University
Cambridge, Massachusetts
Research Field: Biophysics
Photo: Robert Klein/AP, © HHMI
A high-resolution photograph is available on request.
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Enter Xiaowei Zhuang, who makes movies of single molecules in action. Her movies may not play at the local multiplex, but they are illuminating the process by which viruses inject their genome into healthy cells to cause infection, the process by which enzymes adopt a functional form.
Zhuang uses ultrasensitive optical imaging to take snapshots of single molecules and other particles involved in biological processes in real time. Combining this approach with other analytic techniques allows her to investigate the mechanisms underlying intricate biological processes.
By tagging viruses with fluorescent molecules that emit specific colors of light, Zhuang has caught viruses in the act of entering a cell. Visualizing this process allows Zhuang to analyze the individual steps involved in infection, and may help identify targets for new antiviral drugs. Similarly, she is tracing the entry into cells of polymers engineered to deliver genes into cells—a method of gene therapy for diseases like cystic fibrosis, Parkinson’s disease, and certain cancers that scientists hope will be safer and allow better control than viral vectors.
Zhuang’s single-molecule visualization techniques also allow her to study how RNA enzymes fold, assemble, and function. RNA molecules act as catalysts for several essential biological processes and have recently been shown to regulate gene expression, so understanding their architecture and assembly is becoming increasingly important to biology. Among the techniques she is using is fluorescence resonance energy transfer (FRET), in which the transfer of energy between different “donor” and “acceptor” fluorescent tags on different parts of a molecule reveals details about how it undergoes conformational changes as it functions. Techniques such as FRET are enabling Zhuang to capture the dynamic structures of RNA enzymes, as well as the RNA-protein complexes.
Xiaowei Zhuang received her B.S. in physics from the University of Science and Technology of China, and her M.S. and Ph.D. in physics from the University of California, Berkeley. She is Assistant Professor of Chemistry and Chemical Biology and Assistant Professor of Physics at Harvard University. In 2003, she received a MacArthur Fellowship. She was also named “one of the world’s top young innovators” by the MIT Technology Review TR100, a Packard Fellow for Science and Engineering, and an Alfred P. Sloan Research Fellow.
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