MIT, BU engineer cellular circuits that co...( CAMBRIDGE Mass.--MIT and Boston Univ...)

CAMBRIDGE, Mass.--MIT and Boston University engineers have designed cells that can count and "remember" cellular events, using simple circuits in which a series of genes are activated in a specific order.

Such circuits, which mimic those found on computer chips, could be used to count the number of times a cell divides, or to study a sequence of developmental stages. They could also serve as biosensors that count exposures to different toxins.

The team developed two types of cellular counters, both described in the May 29 issue of Science. Though the cellular circuits resemble computer circuits, the researchers are not trying to create tiny living computers.

"I don't think computational circuits in biology will ever match what we can do with a computer," said Timothy Lu, a graduate student in the Harvard-MIT Division of Health Sciences and Technology (HST) and one of two lead authors of the paper.

Performing very elaborate computing inside cells would be extremely difficult because living cells are much harder to control than silicon chips. Instead, the researchers are focusing on designing small circuit components to accomplish specific tasks.

"Our goal is to build simple design tools that perform some aspect of cellular function," said Lu.

Ari Friedland, a graduate student at Boston University, is also a lead author of the Science paper. Other authors are Xiao Wang, postdoctoral associate at BU; David Shi, BU undergraduate; George Church, faculty member at Harvard Medical School and HST; and James Collins, professor of biomedical engineering at BU.

Learning to count

To demonstrate their concept, the team built circuits that count up to three cellular events, but in theory, the counters could go much higher.

The first counter, dubbed the RTC (Riboregulated Transcriptional Cascade) Counter, consists of a series of genes, each of which produces a protein that activat
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