Genome Sequencing Hailed As "New Age In Bacteriology" Michael Purdy -------------------------------------------- JHMI Communications and Public Affairs Aided and advised by a Hopkins Nobel laureate, a group of private researchers has sequenced the entire genetic code, or gen-ome, of an organism for the first time, identifying all the nearly 2 million DNA building blocks that are responsible for the characteristics and activity of a bacterium, Haemophilus influenzae. The achievement may help researchers develop new methods to fight Haemophilus, according to Hamilton Smith, a professor of molecular biology and genetics who was involved with the project. "This is the beginning of a new age in bacteriology," Smith said. "In a few years, we'll have bacteriologists who specialize in studying gene sequences, possibly to find targets for new vaccines or for drugs that treat bacterial infections." Smith, who has studied Haemophilus bacteria for more than 25 years, suggested it for sequencing to private researchers at The Institute for Genomic Research (TIGR). When they agreed, he supplied the necessary raw genetic material. Haemophilus infects approximately 5 percent of humans, normally causing a minor ear infection. In 1978, Smith, interim university president Dan Nathans and a third colleague won the Nobel Prize for isolating special chemicals known as restriction enzymes from Haemophilus. "I knew that a complete map of the Haemophilus genome could powerfully aid my work," Smith said. A genome is the "library" of genes in a particular organism. The process of determining the building blocks making up this library is called sequencing. "When I heard of the genome-sequencing capabilities being developed by Craig Venter, I realized that these new technologies could probably solve the genome in a few months," Smith said. Until now, geneticists typically only sequenced small areas of the genome one at a time. Venter, who founded TIGR, has assembled several dozen automated sequencing machines and developed special software that allows him to "tackle the whole genome in one shot," Smith said. Smith gave Venter many copies of randomly chopped-up segments of the bacteria's genome. Venter's automated sequencers allow him to randomly sequence all of these bits of genetic data; his software then assembles the complete sequence in order. From the results, Venter and Smith have learned that Haemophilus has approximately 1,800 genes. By comparing Haemophilus' genes with genes from other bacteria whose purposes have already been identified, they have deduced the role of approximately 1,100 Haemophilus genes. Identifying the functions of genes in Haemophilus and other bacteria could help researchers pinpoint and disable virulence genes, genes that allow bacteria to cause disease. Genetic code can also reveal important information about the surface of bacteria, helping researchers to design agents that can better attack or bind to these surfaces. Smith is confident that the new approach will soon be applied to other bacteria. "I predict that in two years we'll have 10 bacterial genomes sequenced," he said. "Ultimately, we will know what every gene does in every bacterial cell, and this may give us many new targets for fighting them."