Johns Hopkins Gazette: August 7, 1995

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

     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." 

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