07/27/2000 07:00:00

Caltech receives $1 million grant for Worm Genome Database

PASADENA—In a major follow-up to the sequencing of the human genome, the National Institutes of Health has awarded $1 million to the California Institute of Technology for a genome database to aid in biomedical research as well as basic biology.

Known as the Worm Genome Database, or simply "WormBase," the project will link the already-completed genome sequence of the experimental organism C. elegans to the functions that the genes perform, says Caltech biology professor Paul Sternberg, leader of the project. Also, the information in WormBase will contribute to advances in understanding how genes of all animals are related so that underlying genetic interactions can perhaps be exploited for future treatments of human disease.

More commonly known as a roundworm or nematode, C. elegans has a genome that comprises about 19,000 genes. As a consequence of evolution, the roundworm shares a huge number of genes with human beings—as do all other organisms on Earth, including plants.

The reason this fundamental relationship will be important to 21st-century medicine is that these commonly shared genes, or homologs, often have the same functions in their respective organisms. In Sternberg's own lab, for example, researchers found that several genes that control what cells do during the development of the worm are worm versions of human genes that mutate to cause cancer.

This finding had two implications, Sternberg says. Genes that work together in the worm are likely to work together in the human, and the normal function of "oncogenes" is to control normal cell behavior, not to cause disease.

Thus, improved knowledge of the roundworm at the molecular level could lead to new and improved approaches for dealing with human disease, or even result in a cure.

And as a side benefit, Sternberg says, knowing the differences between ourselves and a roundworm could lead to new approaches to eradicate the creature, which is an agricultural nuisance.

"I think one of the important things about WormBase is that it will lead to new ways to study basic mechanisms," says Sternberg, adding that the sequencing of several other experimental organisms will be important for the same reason. Among the other organisms are the laboratory mouse, the mustardlike flowering plant Arabidopsis, the fruit fly, and the yeast cell.

"We could see patterns emerge from information in different organisms," Sternberg says. "Now that we have the human genome, we can start asking what a certain gene does in humans, what the homolog does in yeast, or fruit flies, or worms, and what's the common denominator."

WormBase's more immediate goals will be to make the genetic information more computer-accessible to anyone interested, Sternberg says. "The standard of success would be that the bench researcher could get within a minute or two the relevant data for his or her own research, rather than go to the library and pore for hours or days through reading materials."

WormBase will continue an existing database developed by Richard Durbin of the Sanger Centre in the United Kingdom, one of two centers that sequenced the worm genome; Jean Theirry-Mieg, now at the National Center for Biological Information; and Lincoln Stein of the Cold Spring Harbor Laboratory. These researchers will remain involved, Sternberg says, as will John Spieth of the Genome Sequencing Center at Washington University in St. Louis, the other sequencing center.

The new phase of the work will involve biologists in curating new data, including cell function in development, behavior, and physiology; gene expression at a cellular level, and gene interactions—in much the same manner that the Human Genome Project will continue now that the genome itself has been completely sequenced. The National Human Genome Research Institute, which is funding this project, also supports databases of other intensively studied laboratory organisms.

Written by Robert Tindol