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.
Enter Xiaowei Zhuang, who makes movies of single molecules in action. Her movies may not play at the local multiplex, but they are illuminating important biological processes, such as those by which viruses inject their genome into healthy cells to cause infection, and those by which enzymes adopt a functional form.
In her pioneering work, 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 light, Zhuang has caught viruses in the act of invading a cell. Visualizing this process allows Zhuang to dissect individual steps involved in infection and to determine the molecular mechanisms underlying these microscopic steps. This knowledge may help identify new drug targets for viral diseases. Similarly, she is tracing the entry into cells of artificial, nonviral vectors engineered to deliver genes into cells—a promising method of gene therapy for diseases such as cystic fibrosis, Parkinson's disease, and certain cancers that scientists hope will be safer and allow better control than viral vectors.
Zhuang also explores single-molecule visualization techniques to study how RNA and ribonucleoprotein enzymes fold, assemble, and function. RNA molecules act as catalysts for several essential biological processes, including protein synthesis. Understanding the architecture and assembly of RNA and ribonucleoproteins is becoming increasingly important to biology. Using single-molecule fluorescence imaging techniques, Zhuang captures the dynamic structures of RNA molecules and RNA-protein complexes in real time and reveals stunning details about how these enzymes fold, assemble and function that are not obtainable by other methods.
