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The Countdown Begins … Bacterial Timekeeping, 1, 2, 3

What happens when you get some of the biggest guns in synthetic biology putting their heads together? Smarter bacteria, according to a study recently published in Nature. The scientists — a Boston-based brain trust that included Boston University’s Jim Collins and Harvard’s George Church —  reported their successful prototyping of two types of “counters” inserted into the genome of E. coli bacteria, both of which turn fluorescent once they’ve counted three discrete chemical signals.

Working with strings of genes and “trip wire” snippets of RNA and DNA, the scientists managed to “cut and paste together … biomolecular components into genetic circuits, just as an electronic engineer uses a soldering gun to put together electronic components on a circuit board,” said Collins, interviewed by Brandon Keim for Wired.com.

While a bacterial counter is itself pretty neat — at least to a biologist — it’s not so much an end in itself as it is a stepping stone to more complex biomachinery, another cool widget to add to the growing catalog of bio-parts available to bioengineers. As basic counting functions underlie even the most complex electronics, a new generation of biomolecular “machines” will also need to rely on some kind of simple cellular numeracy. A reliable counting device built into individual cells would enable bioengineers to program sequential functions into synthetic biological systems — allowing them not just to turn a process on or off, but to set it to run on its own through a given cycle. The difference between, say, a light switch and a multi-setting digital timer.

The ability to count could enable bacteria to signal repeated spikes in the level of a given environmental contaminant, or send a warning about the rampant cell growth associated with cancer. An immediate application of in-cell counters would be as a safety “kill switch” to prevent engineered organisms from going renegade. Interviewed by sci-fi (and occasionally just plain “sci”) blog i09, Stanford’s Christina Smolke, another synthetic biology luminary who was not involved in the study but wrote an analysis of it, explained: “If one is releasing an engineered microorganism into the environment, you could use this counter to trigger its death after a certain number of cell divisions to provide better control over the engineered system and less chance for spreading from the intended application.”

The prototype counters can only count up to three, but the authors claim their capacity can be expanded. It will certainly be interesting to see how others will pick up on these new parts and, ultimately, incorporate them into truly useful tools, whether in medicine, bioremediation, or some area as yet unforeseen. Only time will tell.

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