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Lab Quickens Evolution

By Matthew T. Lowe, Contributing Writer

Harvard laboratory researchers, led by Professor of Chemistry and Chemical Biology David R. Liu ’94, have found a new and faster technique of directed evolution, generating biomolecules with certain desired properties, by co-opting the life cycle of a bacteriophage.

Their paper, entitled “A System For The Continuous Directed Evolution Of Biomolecules,” was published this month in the journal Nature.

The researchers created a system named “phage-assisted continuous evolution,” called PACE, in which genes are transported between host cells of E. coli through a bacteriophage and undergo multiple rounds of continuous evolution.When a single round of traditional directed evolution takes days to complete, research that requires hundreds or thousands of rounds could take years.

PACE promises to speed up this process by nearly 100-fold.

“In the past, directed evolution has been constrained by the relatively slow speed and labor-intensive nature of most conventional methods,” Liu said.

“The purpose of this research is to develop a new method of directed evolution that dramatically speeds up the process by removing the requirement of researcher intervention from virtually every step of the cycle,” he added.

Liu, a Harvard College Professor and an investigator with the Howard Hughes Medical Institute, worked closely with Kevin M. Esvelt and Jacob C. Carlson, two graduate students who co-authored the paper.

Esvelt and Carlson have spent a combined nine years on the project.

Having now developed a general method for evolving proteins, the group’s next goal is to find techniques that can target more specific biomolecules.

“The fact that we can do this very quickly would have very powerful therapeutic applications,” Carlson said.

Liu also alluded to even broader implications of their work.

“In our lab, much of the research is inspired by biological evolution,” Liu said. “We’re using PACE to answer some basic evolutionary questions that would usually demand years to address.”

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