September 05, 2015

Taking synthetic biology to next level with engineered multicellular cooperation

Instead of engineering cells to work as tiny individuals, researchers are working on a new class of cellular machines that “talk” to each other – and behave in more sophisticated ways. Put simply, synthetic biology is going multicellular.

“Initially, there was more emphasis on engineering individual cells and real progress was made,” says Ron Weiss at the Massachusetts Institute of Technology. “But now there are an increasing number of demonstrations showing what’s possible with multiple cells. It’s another dimension.”

The latest example comes from a team led by Matthew Bennett at Rice University in Houston, Texas. They developed a system that at its simplest encourages cooperation between two distinct populations of Escherichia coli. One produces an “activator” signalling molecule that triggers the bacteria in the second population to produce a “repressor”. This signal can travel the other way and turn off production of the activating molecule

The team also engineered the E. coli so they would fluoresce depending on the strength of the signals. What’s interesting is the sophisticated way the two populations respond. They found that about every two hours, the cells in both populations fluoresced more and more, before gradually fading away again

Team work: three ecoli cells working togetherRon Weiss/SP

Science mag - Emergent genetic oscillations in a synthetic microbial consortium




Abstract

A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types—an “activator” strain and a “repressor” strain. These strains produced two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way toward engineering complex synthetic tissues and organs with multiple cell types.

Engineering cell population behavior

Attaining the full promise of synthetic biology will require designing population-level behaviors of multiple interacting cell types. As a start, Chen et al. engineered two strains of the bacterium Escherichia coli to produce signaling molecules that regulate transcription in the complementary strain (see the Perspective by Teague and Weiss). The signaling circuit was successfully designed to produce feedback loops that produce synchronous oscillations in transcription between the two strains. A mathematical model helped determine how to modulate the oscillations and control their robustness to perturbations.

20 pages of supplemental material

SOURCES - New Scientist, Journal Science

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