To preserve the tips of chromosomes, telomerase uses a protein enzyme called telomerase reverse transcriptase, or TERT, and a short stretch of RNA that serves as the enzyme's instruction sheet. The two components, however, can't seem to interact properly with each other on their own; helper proteins are needed to promote their assembly into a functional complex.

To find out how one helper protein called p65 helps choreograph the movements that bring together TERT and telomerase RNA, Zhuang and her collaborator, Kathleen Collins, a telomerase biochemist at UC Berkeley, used a technique known as fluorescence resonance energy transfer (FRET). Researchers label the molecule at precise locations with two dyes that emit distinct colors of light. One of these dyes can transfer energy to the other; how much is transferred depends on how close together the two dyes are.

Zhuang and her colleagues attached FRET labels to telomerase RNA and, by monitoring changes in the energy transfer between the labels, observed step-by-step changes in the assembling complex. Their data showed that p65 kicks off the process by binding to the RNA, flexing it so that its TERT binding sites are close together. TERT can then latch on, snapping the RNA into its final, functional form. "It's like a jigsaw puzzle," Zhuang says. "When you put in one piece, it helps another find its proper place."

With experiments like these, Zhuang says biophysicists and biologists are steadily moving their field toward the kind of fundamental and quantitative ways of explaining the world that first attracted her to science. She acknowledges, however, that biology's underlying elegance will differ from that found in physics. "We don't necessarily want to strip away all the complexity of biology, to say 'here are the bare bones and now it's simple,'" she says. "But a different way of viewing that complexity may emerge, to allow us to understand the connections and interplay between biology's many components."

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