The right time and place led to a new RNAi-like pathway in bacteria.

Though their labs at University of California, Berkeley, are only a few buildings apart, biochemist Jennifer Doudna and geobiologist Jill Banfield were strangers. But when Banfield needed expertise outside her scope, their worlds converged.

Banfield studies microbes that grow in extreme environments. She needed a partner who knew about the gene-silencing process known as RNA interference (RNAi).

Doudna, an HHMI investigator who studies RNAi in eukaryotic cells, had solved the crystal structure of Dicer, a key enzyme in that process.

Realizing her luck at having a resource so close by, Banfield called Doudna to discuss what appeared to be a microbial gene-silencing strategy analogous to RNAi that was accomplished by highly repetitive DNA sequence elements known as CRISPRs—an acronym for clustered regularly interspaced short palindromic repeats.

Banfield and others suspected that microbes were using CRISPRs to fend off invaders. But nobody knew how CRISPRs could function as an immune system, and scientists were intrigued by what else the tiny bits of RNA derived from CRISPRs might be doing.

The two researchers met for coffee a few times in 2006 and explored the overlap between their worlds. Those conversations and the well-timed arrival of two new lab members led to Doudna's team capturing the first snapshot of a CRISPR enzyme in action. They reported in September 2010 that the CRISPR-associated enzyme Csy4 has the unusual property of recognizing, binding to, and cleaving RNA in a sequence- and structure-specific way.

"As often happens in science, there is a lot of serendipity involved," Doudna acknowledges.

Illustration: Nick Tassone

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