Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [98]
Schultz and his colleagues have found a way around this shortcoming. Instead of adding the sugar after a protein is built, they add it to individual amino acids. They then engineer E. coli to recognize the unnatural sugarcoated amino acids instead of the ones it normally uses. In this arrangement the bacteria can assemble proteins with sugar knobs already in place, ready for human consumption. What is unnatural for E. coli turns out to be quite natural for us.
NETWORK HACKS
For all the futuristic aura around genetic engineering, the science is rather quaint. It is based on a 1950s view of biology. In the world of genetic engineering, E. coli and other species are nothing more than simple chemical factories manufacturing their own sets of proteins. Change a gene and you change one of the proteins that comes out. Genetic engineers are well aware that there is much more to life than the production of proteins. There are repressors and promoters, for example, which turn genes on and off. But many genetic engineers use these insights only to make E. coli and other organisms into even better factories.
There’s another way to look at E. coli: as a network. Its proteins and genes work together, allowing the microbe to process information, to make decisions, to keep its biology steady in an unsteady world. The powers of this network emerge from the sum of its parts, not from any one gene or protein. Engineers regularly improve on man-made networks—rewiring circuits, swapping parts. If life follows engineering principles as well, some scientists wonder, would it be possible to rewire life, too?
The first two reports of rewired life came in 2000, and in both cases the life in question was E. coli. Michael Elowitz at California Institute of Technology and Stanislas Leibler of Rockefeller University in New York made the microbe blink. They used three genes to build a circuit. Each gene made a different repressor. Elowitz and Leibler engineered the first gene so that its repressor shut down the second gene. The repressor made from the second gene shut down the third. The third shut down the first, but it also did something else: it caused E. coli to build a glowing-jellyfish protein.
Elowitz and Leibler found that in some of their engineered microbes, the three repressors became locked in a cycle. As the first gene made more and more repressors, it shut down the activity of the second gene, freeing the third gene to shut down the first one. As the first one stopped making its repressor, the second gene was freed and shut down the third gene, and so on. Elowitz and Leibler arranged these genes on a plasmid and inserted them in E. coli. As the genes became active, the scientists could witness this cycle with their own eyes: as the third gene switched on and off, it produced more and then less light. In other words, E. coli blinked.
The second report came from the laboratory of James Collins at Boston University. Collins and his colleagues gave E. coli a toggle switch. They built two genes, each encoding a repressor that shut off the other gene. Each repressor could be pulled off E. coli’s DNA by adding a different molecule to the microbe. To observe how this new circuit of genes worked, Collins and his colleagues, like Elowitz and Leibler, added instructions to one of the genes for building a glowing protein. Adding one kind of molecule caused E. coli to start glowing and to continue glowing even after the molecule had run out. Adding the other kind of molecule shut the glow down and kept E. coli dark even after it, too, had run out.
These experiments are now recognized as marking the birth of a synthetic