The project represents the efforts of a consortium: the Cystic Fibrosis Foundation, the University of Washington (UW) Genome Center and Seattle-based PathoGenesis Corp.
"We hope that this innovative new project will greatly increase our practical knowledge about the pathogen which is so pervasive in CF patients," said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation. "In essence, the project should reveal specific sites in the bacterium's genetic structure to target the development of exciting new drugs." He continued, "Every member of this consortium shares a common goal ( to always keep the practical application of the information for patients in mind."
The worldwide research community will now have rapid access to the genetic data as it is collected by consortium scientists. The genetic sequencing information will be updated every quarter on the Internet, starting the fourth quarter of 1997. Access to the Genome data will liberate investigators from duplicating their efforts or from performing costly piecemeal DNA sequencing.
P. aeruginosa causes chronic lung infections, lung damage and respiratory failure in most people with CF, a fatal genetic disease that occurs in one in every 3,300 live Caucasian births in the United States. The bacterium has a remarkable capacity to cause disease, thriving in a wide variety of environments even when nutrients are limited. In the lungs, P. aeruginosa often acquires a mucoid capsule which protects it from antibiotics and the body's natural defenses.
The consortium estimates that it will take two years to "sequence" between 5,000-6,000 genes in the most frequently studied strain of P. aeruginosa, called PAO1. The genome sequencing process begins when scientists at UW and PathoGenesis extract small bits of pseudomonas DNA and propagate them in the laboratory. They then analyze the DNA through sophisticated sequencing equipment. Computer programs then take this raw data and assemble it into t he genetic map of the organism.
In essence, the research determines the order of the chemical building blocks of the bacteria's DNA. Computers help to identify the likely function of the genes by comparing them with known genes from other organisms.
Researchers anywhere in the world can take a "query" sequence from a bacterium that they are studying and type that into the new Web site. A computer program will then go through all the reference data and see if there are any sequences similar in pseudomonas. This ability to find similarities pushes biological knowledge ahead by leaps and bounds.
"We are able to produce raw DNA sequencing data of such high quality that it is of immediate value for clinical research before completing the analysis of the full pseudomonas genome," said Maynard V. Olson, Ph.D., who directs the University of Washington Genome Center. "This is the largest bacterial genome sequencing ever to be undertaken."
"The public release of data from this project represents a landmark for our center," continued Olson. "It shows that with strong leadership from the Cystic Fibrosis Foundation, the Office of Technology transfer at UW, and the Washington Technology Center, and PathoGenesis, it is possible to make public-private partnerships work quickly, efficiently and economically."
Armed with knowledge about the complete bacterial genome, researchers will gain new insights into how and why P. aeruginosa lives so tenaciously under sub-optimal conditions. Full DNA sequencing should identify functions of the bacteria previously unknown, and suggest new avenues of action for drugs to treat these infections. For example, there are genes that control the bacterium's attachment to the host tissue, genes that tell it to build colonies, and genes that actually trigger a mechanism to pump antibiotics out of infected cells.
"Public-private partnerships are vital to discovering new treatments for diseases like CF," said Wilbur H. Gantz, CEO of PathoGenesis. "We believe that our investment in basic research on pseudomonal infections can lead to unique therapies in the years ahead."
The Cystic Fibrosis Foundation is a voluntary non-profit health organization. Its mission is to develop the means to cure and control CF while improving the quality and duration of life for those with the disease today. (www.cff.org).
The University of Washington Genome Center is recognized for its large-scale production of genome mapping and sequencing data. (www.genome.washington.edu).
PathoGenesis Corp. develops drugs for treating serious infectious diseases where there is a significant need for improved therapy. The company is developing drug candidates to treat chronic lung infections in CF and bronchiectasis patents as well as tuberculosis infections. (www.pathogenesis.com). The company recently filed a new drug application with the Food and Drug Administration for TOBI TM (tobramycin for inhalation) to treat chronic lung infections in individuals with CF.
For press inquiries contact, Carolyn Habbersett, CFF, (301) 951-4422; Laurie McHale at UW, (206) 543-3620, or Maryellen Thielen at PathoGenesis Corp., (847) 583-5424.