Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [21]
Our bodies are robust in all sorts of ways. Our brains need a steady supply of glucose, but we don’t black out if we skip dinner. Instead, our bodies unload reserves of glucose as needed. A clump of cells develops into an embryo by trading a flurry of signals to coordinate their divisions. The signals are easily disrupted, but most embryos can still turn into perfectly healthy babies. Again and again life avoids catastrophic failure and remains on course.
Until recently, scientists had no solid evidence for where life’s robustness comes from. To trace robustness to its source, they needed to know living things with a deep intimacy—the same intimacy an engineer may have with an autopilot system, using its plans to carry out experiments. But the blueprints of most living things remain classified. Among the few exceptions is E. coli.
E. coli faces threats to its survival on a regular basis. Set a petri dish on a windowsill on a sunny day and you bring the microbes in it to the brink of disaster. In order to work properly, a protein needs to maintain its intricate origami-like folds. Overheated proteins shake themselves loose. They can no longer do the job on which E. coli’s survival depends.
Yet E. coli does not die from a few degrees of extra heat. As the temperature rises, the microbe makes molecules known as heat-shock proteins. They defend E. coli in two ways. Some of them embrace E. coli’s jittery proteins and guide them back into their proper shape. Others recognize heat-snarled proteins that have been damaged beyond repair. They slice these hopeless proteins apart, leaving harmless fragments to be recycled.
Heat-shock proteins are lifesavers, but E. coli can’t keep a supply of them on hand for emergencies. They are among the biggest proteins in its repertoire, and to survive a blast of heat E. coli may need tens of thousands of them. Making heat-shock proteins in ordinary times would be like paying the local fire company to park all its trucks in your driveway just in case your house catches fire. On the other hand, when you need a fire truck, you need it fast. If E. coli takes too long to manufacture heat-shock proteins, it can die while it waits to be rescued.
This tricky trade-off attracted the attention of John Doyle, an engineer at the California Institute of Technology, and his colleagues. In past years, Doyle had developed a theory for designing control systems for airplanes and space shuttles. In E. coli he recognized a piece of natural engineering just as impressive as anything he had helped to build. He and his colleagues began to analyze its heat-shock proteins and the way E. coli uses them to survive.
They found that E. coli controls its supply of heat-shock proteins with feedback. For engineers, feedback is what happens when they allow the output of a circuit to become an input. A thermostat uses a simple form of feedback to keep the temperature of a house stable. The thermostat senses the temperature in the house and turns on the heater if it’s too cold. If the temperature gets too high, it shuts the heater down.
E. coli’s defense against heat works a lot like a thermostat as well. The key protein in its thermostat is called sigma 32. Even when the temperature is cool, E. coli is constantly reading the gene for sigma 32 and making RNA copies. But at normal temperatures the RNA folds in on itself, and so E. coli cannot use it to make a protein. At normal temperatures the microbe is loaded with sigma 32 RNA but no actual sigma