All cell biologists have at least "two cells of interest," wrote biologist Frederick Neidhardt of the University of Michigan, Ann Arbor, in 1996: "the one they are studying and Escherichia coli." The lowly intestinal bacterium has been an indispensable tool for half a century. Now it is the object of a mammoth international modeling effort that is expected to occupy hundreds of scientists for 10 years at a cost of at least $100 million.
Scientists around the world are busy computerizing models of parts of cells, but as yet there is no computer model of an entire living cell and all its functions, says Barry Wanner of Purdue University in West Lafayette, Indiana. This month, a group of scientists spearheaded by Wanner launched an international alliance to consolidate global E. coli modeling efforts, dubbed the International E. coli Alliance.
"This will be a major breakthrough if we can solve a simple cell," says Wanner, who heads the main U.S. piece of the action, the E. coli Model Cell Consortium, created in March. Other advocates say the project dwarfs the Human Genome Project. "It is 10 times more ambitious and 100 times more important for mankind," claims Hans Westerhoff, who heads the Silicon Cell modeling effort at the Free University in Amsterdam. Westerhoff explains that the genome project and related work is like a complete catalog of car parts. The E. coli model will show how the pieces fit together. If the work proceeds as expected, "all interactions between genes, proteins, and small molecules will be revealed, and the whole cellular network will be reconstructed," says Igor Goryanin, who heads cell modeling at GlaxoSmithKline in Stevenage, U.K.
George Church, a computational geneticist at Harvard University, says that with a complete computer model, "you can run through changes that might take hundreds of years in the lab." It will enable scientists working on their desktops to create various mutants and introduce genes from other organisms to see which would be most relevant for work on a new antibiotic, for example. Some of the money from the project will come from existing grants, but researchers hope to attract new funding too: Wanner's group, for example, has asked the National Institutes of Health for $20 million for the U.S. leg of the venture.