This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Scientists often describe life as a series of chemical reactions. Pallav Kosuri, Ph.D., describes life as movement.
Chemical reactions are how you drive the movement of atoms, proteins, cells and bodies—without movement, there is no life. "If you don't know how something moves, you don't know what it does," says Kosuri. "And if you want to understand, manipulate and alter the function of molecules, understanding their physical movements is just as important as understanding their chemical reactions.
The difference is: We have a comprehensive catalog of the chemical reactions, while the mechanical side is still the Wild West." Kosuri's lab is setting out to change that. They started with DNA origami, a method that uses DNA building blocks to create custom, self-assembling nanostructures with a range of applications—drug delivery, lab-on-a-chip devices and now foundational biological discovery. Then they developed ORBIT, a method that uses DNA origami to build fluorescent nanostructures for visualizing molecular movements.
Technical limitations have long made it difficult or impossible to measure molecular movement over extended periods. Fluorescence microscopy is a powerful technology, but observation times are limited by the amount of time fluorescent tags remain bright—over time, they always go dark. Their latest work, published in Cell Reports Methods, overcomes this challenge with a "dye-cycling" strategy for ORBIT that constantly replenishes fluorescent tags, extending the measurement time window from seconds to hours.
This allowed them to measure the rotation of a single RNA polymerase molecule as it "reads" DNA with base-pair resolution and over unprecedented lengths of time. The new method could provide critical mechanical insights into how genes are transcribed in cells. The DNA inside each cell is the result of billions of years of evolution and optimization.
The structure of DNA relies on complementary nucleic acids, represented in shorthand as A, T, C and G. Each nucleic acid "letter" has a partner that it interlocks with (A with T; C with G) to create the iconic ladder-like double helix. The unique ability for DNA strands to associate and assemble with one another inspired an idea decades ago: What if we used DNA's innate architectural elements to build structures other than the double helix?
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