Team work: three cells are better than one Ron Weiss/SP

HARDER, better, faster, stronger. When cells cooperate, they achieve the otherwise impossible, something that could eventually lead to smart cancer therapies.

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 (Science, doi.org/66b).

“Sophisticated behaviour occurs only when the different E. coli strains communicate”

“If you grow just one of these strains by itself, nothing happens,” says Bennett. Only when the two populations communicate does this oscillating behaviour appear. Such an oscillator could be used as a molecular timer but more significantly, it is proof of principle of the complexities that emerge when cells – whether mammalian or microbial – are persuaded to communicate.

And interacting systems could prove very useful indeed, says Joshua Leonard at Northwestern University in Evanston, Illinois. For instance, a cellular population is collectively much more aware of its surroundings than any individual cell. “You might get more accurate processing of environmental signals and therefore more robust decision-making,” says Leonard. That could make multicellular synthetic biology useful in industry.

For example, unicellular microbial systems already churn out chemicals and pharmaceuticals in fermentation vats. Perhaps a multicellular version could continue to work efficiently even if conditions in the vats began to alter.

Multicellular synthetic biology could also become a big player in medicine. “The medium-term goal is working with systems like the gut microbiome, in which we can deploy cells to report about or alter their environment,” says Bennett. There has already been some success using engineered cells to patrol our guts. These cells might become even better at diagnosis and treatment if they begin to communicate with one another and with other microbes in the gut.

Cancer could be another target. “You might want your engineered cells to figure out whether they are sitting next to a tumour or not – and if so, release a drug,” says Leonard, who recently described a technology that will allow mammalian cells to interact with multicellular networks in their environment (ACS Synthetic Biology, doi.org/659).

“It’s clear that fully exploiting the unique capabilities of living cells will ultimately require us to go multicellular,” says synthetic biologist Michael Elowitz at Caltech in Pasadena.

This article appeared in print under the headline “Chatty bugs take cellular machines to new heights”