Even 'simple' organisms guard family secrets from researchers

Microbiologists were both thrilled and dismayed in 1997 when the genetic sequence of Escherichia coli strain K-12, arguably the most thoroughly studied organism on Earth, was finally identified. Their favorite bug, it turns out, has 4,639,221 pairs of DNA bases and 4,288 genes.

"But of those genes, 38 percent -- more than 1,600 -- have no identifiable function despite years of intensive research," says Stephen Zinder, chair of the Department of Microbiology. "Clearly we still have a lot to learn about even the extensively studied organisms."

Today a total of 16 microbial genomes have been sequenced, and about 50 more are in progress at laboratories around the world. "As these genomes are sequenced, we're finding at least one-third of the genes don't look like anything we've seen before," Zinder says. "Or if they look like genes of other organisms, we don't know what those genes do."

Not that microbiologists aren't grateful for the information bounty that genomics is bestowing. But there is still a lot of manual work to identify what these genes actually do, Zinder says. As more genes are identified, microbiologists will be able to work backwards in a kind of "reverse physiology" and learn surprising new things about the organisms that direct observation never allowed.

This new field has become known as microbiological genomics. And while it has yet to form a specific area for study, students are leaving Cornell with the essential basics of the subject. Karen Nelson, for example, a Ph.D. graduate from animal science, is now at the Institute for Genomic Research and is deciphering the genome of Thermotoga, a bacterium that grows at 90 degrees Centigrade and degrades cellulose. Meanwhile at Cornell, faculty researchers are documenting the family history of some special-interest microorganisms:

• Food scientist Carl Batt is taking the genomic approach to the study of lactic acid bacteria.

• Microbiologist Stephen Winans is deciphering the genetic code of a virulence plasmid in Agrobacterium tumefaciens, which "shoots" DNA into plants to cause crown gall tumors, but also can be used to engineer transgenic plants.

• Microbiologist James Russell, the rumen microbe specialist whose discoveries about acid-resistant E. coli could lead to a safer food supply, now hopes to pinpoint genes that let the bacterium evade human stomach acids.

Zinder has his own pet microorganism: Coccoid strain 195, which shows promise as a bioremediation agent and was discovered in an Ithaca sewage treatment plant. Zinder hopes the genomic approach will help answer the question: What's a nice bug like you doing in a place like this?