High Confidence Prediction of Essential Genes in Burkholderia Cenocepacia
1236 C R E D IT : M A R IE W U BOSTON—“We’re going into the inner sanctum,” says George Church, gliding through a series of doors and passages, waving his key card to get in. At the center of this labyrinth in Harvard University’s Wyss Institute for Biologically Inspired Engineering is a tiny locked room that Church opens with an old-fashioned metal key. Inside is a device that the 57-year-old biologist invented and built with the help of a local robotics company. He calls it MAGE, and it does look slightly magical, as if the contents of a molecular biology laboratory have fl own off the benches and arranged themselves into a box. The effect is enhanced as Church— nearly 2 meters tall with an impressive wizard’s beard—looms over the desk-sized contraption. But the real magic comes with what MAGE does: Millions of normal Escherichia coli bacteria go in one end; a vast menagerie of microbes with new genomes comes out the other end. “I’m hoping this thing will be worth $200 billion,” he says. A statement like that isn’t unusual for Church. It sounds brash at fi rst, but laboratories around the world are trying to genetically alter bacteria and other kinds of cells to make industrial chemicals from biomass effi ciently, and the potential payoff is huge. Church argues that MAGE, which stands for multiplex automated genome engineering, will be an indispensable tool for doing that. In a debut of the technology several years ago, Church produced billions of different versions of the E. coli genome, identifying one that is fi ve times more effi cient at producing the antioxidant lycopene (Science, 21 August 2009, p. 928). “That was just a proof of concept,” he says. Now he’s setting his sights on more lucrative chemicals, such as dyes, and also on enabling MAGE to refashion nonbacterial genomes. Synthetic biology, with its goal of reengineering cells as industrial machines, is the epitome of ambition. But even in a fi eld of risk-takers, Church stands out. “He always talks about such wild experiments,” says J. Christopher Anderson, a synthetic biologist at the University of California, Berkeley, and one of Church’s collaborators. “And then he rolls them out. He actually makes some of them work.” Church’s scientific risk-taking has paid off. Earlier this year, Church was elected to the U.S. National Academy of Sciences. He is one of four scientists sharing a $20 million grant from the U.S. National Institutes of Health to develop effi cient ways to change the genetic makeup of stem cells as a way of treating disease. Church has also helped to create or guide more than two dozen start-up companies and generated 34 biotechnology patents himself—not to mention leading the charge in personal medicine with his Personal Genome Project, in which he and others voluntarily bared their genomes (Science, 21 December 2007, p. 1843). “There are people who are good at identifying the problems for the fi eld, and there are others who are good at doing the experiments,” says Jason Chin, a molecular biologist at the University of Cambridge, U.K. Church is rare in that “he does both.” But whether Church can pull off his most ambitious experiment—reinventing the genetic code—is another question. If he succeeds, biotechnology will have a new workhorse cell. And the planet will have a novel life form.