Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [22]
Only when E. coli heats up can the sigma 32 RNA uncrumple. Now the ribosomes can read it and make huge amounts of sigma 32 protein. Each sigma 32 protein quickly finds some of E. coli’s gene-reading enzymes and leads them to the genes for heat-shock proteins. E. coli thus makes tens of thousands of heat-shock proteins in a matter of minutes.
Left unchecked, however, a sudden rush of sigma 32 would be too much of a good thing. The microbe would churn out heat-shock proteins far beyond its needs. In fact, E. coli makes just the right number of heat-shock proteins to cope with a particular temperature. It makes more proteins for higher temperatures, fewer for cooler ones. It exerts this fine control with a series of feedback loops.
E. coli’s heat-shock proteins don’t just protect against heat. They also control the thermometer protein itself, sigma 32. Some of them grab sigma 32 and tuck it away in a pocket. Others cut it to pieces. In the first few moments of dangerous heat, heat-shock proteins are too busy helping unfolded proteins to attack sigma 32. But once they get the crisis under control, more and more heat-shock proteins become free to grab sigma 32. As the level of sigma 32 drops, E. coli makes fewer new heat-shock proteins.
This feedback helps keep E. coli from exploding with heat-shock proteins. It also controls the level of heat-shock proteins. If E. coli is merely warm rather than scorching, the heat-shock proteins quickly reduce the level of sigma 32. But as the temperature increases, they have to cope with more unfolded proteins, and thus they allow sigma 32 to remain high so that E. coli will produce more heat-shock proteins. And once E. coli cools down to a comfortable temperature, its thermostat shuts down the heat-shock proteins almost completely.
E. coli’s robust self-control comes from the feedback loops built into its network. To engineers this principle is second nature. The autopilot in a Boeing 777 uses the same kinds of feedback to keep the plane level as it is buffeted by wind shears and downdrafts. In neither case does robustness come from some all-knowing consciousness. It emerges from the network itself.
THE BIG PICTURE
Put genes together into circuits and they can do much more than they could on their own. Put circuits together and you create a living thing.
In the 1940s, Edward Tatum and other scientists got the first hints of what certain genes in E. coli were for. As of 2007, researchers had a pretty good idea of what about 85 percent of its genes do, making E. coli the gold standard of genetic familiarity. Scientists have created online databases for E. coli’s genes, its operons, its metabolic pathways. Mysteries remain—there are forty-one enzymes drifting around inside E. coli for which scientists have yet to find genes, for example—but a rough portrait of E. coli’s entire system is emerging, the closest thing biologists have to a complete solution to any living organism.
Bernhard Palsson, a biologist at the University of California, San Diego, has overseen the construction of a model of E. coli’s metabolism. As of 2007, he and his colleagues had programmed a computer with information on 1,260 genes and 2,077 reactions. The computer can use this information to calculate how much carbon flows through E. coli’s pathways, depending on the sort of food it eats. Palsson’s model does a good job of predicting how quickly E. coli will grow on a diet of glucose and how much carbon dioxide it will release. If Palsson switches off the oxygen, the model shunts carbon into an oxygen-free metabolic pathway, just as E. coli does. If Palsson leaves out a particular protein, the model metabolism rearranges itself just as the metabolism of a real mutant E. coli would. It predicts E. coli’s behavior in thousands of conditions. The model and E. coli alike make the best of whatever situation they face, adjusting their metabolism in order to grow as fast as they can.
How does E. coli’s metabolism manage to stay so supple when it is made up of hundreds of chemical reactions? With thousands