Rec-Stop-Play: CRISPR becomes a biological recorder

biological recorder 2When using a standard tape recorder you just have to press the buttons. Now a Columbia University team has devised a system for doing the same in living systems, recording changes taking place inside the cells. How does it work? This biological recorder, described in a study appearing in Science, is called TRACE and may help us chronicle what happens in open settings such as marine environments or in habitats difficult to access such as the mammalian gut. It records molecular fluctuations instead of sounds, capturing metabolic dynamics, gene expression changes and lineage-associated information across cell populations. The medium is DNA rather than magnetic tape. Sequencing is like playing. But how is the DNA recording done?

TRACE is an acronym meaning “temporal recording in arrays by CRISPR expansion.” The Rec function, in fact, is carried out by CRISPR, the immune system used by bacteria to detect and destroy invading viruses. When talking about CRISPR, we usually refer to its genome-editing application which is based on warrior protein Cas9. This time, however, researchers focused on two less-known components of the CRISPR system, called Cas1 and Cas2. In nature they keep note of the “most wanted” viruses, inserting their genetic identikits as spacers into the bacteria genomic archive. As spacers are integrated in order of appearance, DNA becomes a kind of timeline.

Ravi Sheth and colleagues have built up their biological recorder by inserting the genes coding for Cas1 and Cas 2 into a recording unit (plasmid pRec). Another unit (pTrig) provides the “trigger spacers” to be encoded into the bacterial genome when exposed to a select signal. When there’s no signal, reference spacers are acquired at a background rate serving as time intervals. Therefore the succession of spacers represents a memory system storing chronologically biological events.

biological recorder GIF

To test the system’s multiplexability, researchers simultaneously recorded the availability of three chemicals in Escherichia coli bacteria: a heavy-metal contaminant (copper), a dietary sugar metabolite (trehalose) and a molecule associated with gut infection (fucose). TRACE worked well, chronicling the three different biological signals over the course of three days. CRISPR’s massive potential as a data storage system was spectacularly demonstrated a few months ago by George Church. That study was considered a proof of concept for a future where cellular recorders will collect and store cells memories. It seems the future is coming.

(Photo credit: Ravi Sheth)

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