Cell Signaling Neither Random Or Chaotic - Just Exceedingly Complicated

quanta |  Back in 2000, when Michael Elowitz of the California Institute of Technology was still a grad student at Princeton University, he accomplished a remarkable feat in the young field of synthetic biology: He became one of the first to design and demonstrate a kind of functioning “circuit” in living cells. He and his mentor, Stanislas Leibler, inserted a suite of genes into Escherichia coli bacteria that induced controlled swings in the cells’ production of a fluorescent protein, like an oscillator in electronic circuitry.

It was a brilliant illustration of what the biologist and Nobel laureate François Jacob called the “logic of life”: a tightly controlled flow of information from genes to the traits that cells and other organisms exhibit.

But this lucid vision of circuit-like logic, which worked so elegantly in bacteria, too often fails in more complex cells. “In bacteria, single proteins regulate things,” said Angela DePace, a systems biologist at Harvard Medical School. “But in more complex organisms, you get many proteins involved in a more analog fashion.”

Recently, by looking closely at the protein interactions within one key developmental pathway that shapes the embryos of humans and other complex animals, Elowitz and his co-workers have caught a glimpse of what the logic of complex life is really like. This pathway is a riot of molecular promiscuity that would make a libertine blush, where the component molecules can unite in many different combinations. It might seem futile to hope that this chaotic dance could convey any coherent signal to direct the fate of a cell. Yet this sort of helter-skelter coupling among biomolecules may be the norm, not some weird exception. In fact, it may be why multicellular life works at all.

“Biological cell-cell communication circuits, with their families of promiscuously interacting ligands and receptors, look like a mess and use an architecture that is the opposite of what we synthetic biologists might have designed,” Elowitz said.

Yet this apparent chaos of interacting components is really a sophisticated signal-processing system that can extract information reliably and efficiently from complicated cocktails of signaling molecules. “Understanding cells’ natural combinatorial language could allow us to control [them] with much greater specificity than we have now,” he said.

The emerging picture does more than reconfigure our view of what biomolecules in our cells are up to as they build an organism — what logic they follow to create complex life. It might also help us understand why living things are able to survive at all in the face of an unpredictable environment, and why that randomness permits evolution rather than frustrating it. And it could explain why molecular medicine is often so hard: why many candidate drugs don’t do what we hoped, and how we might make ones that do.