Cellular rhythms: A rock-paper-scissors circuit

Video Transcript:

The inner workings of cells are often very complicated, with many molecules doing different things at different times. At the heart of this activity are proteins, whose concentrations rise and fall as the cell goes about its business.

To learn about these protein oscillations and how to engineer cells to do new things, scientists created a simple cellular oscillator. They called it the repressilator and stuck it into the bacterium E. coli. The repressilator is a little loop of DNA with three genes. It works like rock-paper-scissors. Each gene generates a protein that turns off or represses the next gene, like paper covering and repressing rock. So when Gene No. 1 — we’ll call it “rock” — is on, it starts generating a protein. That protein turns off Gene No. 2. We’ll call Gene 2 “scissors.”

When the scissors gene is active, it generates a protein that turns off the third gene. We’ll call it “paper.” But when rock’s protein turns off scissors, our paper gene is freed up to make its protein. Paper’s protein then builds up and, you guessed it, it turns off rock. With rock turned off, Gene 2, scissors, starts making protein again, and scissors protein turns off the paper gene. Ta-da! Rock is now freed up and the cycle starts again.

How did the scientists know that their little oscillator was working? They introduced another gene into the bacterium that, when active, makes a protein that glows green. This gene, just like scissors, gets turned off by rock’s protein. So as the levels of the rock protein oscillate, so do the levels of the green fluorescent protein.

The scientists could see their clock’s oscillations as the bacteria slowly pulsed green, on and off. The effort has helped scientists understand how biochemical clocks work in natural cells. It’s also paved the way for building more complicated cellular circuits, with the aim of creating microbes with brand-new capabilities.