Center News

Front line on biological defense

Oct. 2, 2003
Drs. David Baldwin and Nina Salama in the lab

Drs. David Baldwin and Nina Salama will develop vaccines for potential bioweapons.

Photo by Todd Mcnaught

Fred Hutchinson researchers will play a key role in a $50 million biological defense center to develop vaccines for infectious diseases that pose current or future threats to public health.

The WWAMI (Washington, Wyoming, Alaska, Montana and Idaho) Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, led by the University of Washington, is one of eight centers established by the federal Department of Health and Human Services. The overall initiative will receive approximately $350 million dollars in support over 4.5 years from the National Institute of Allergy and Infectious Diseases (NIAID).

Dr. Samuel Miller, professor of medicine, microbiology and genome sciences at the UW School of Medicine, is principal investigator of the WWAMI project, which will also involve investigators at thirteen other institutions in the region.

Dr. Nina Salama, an investigator in the Human Biology Division, will lead the biodefense center's project to identify potential vaccine targets for the bacterium Yersinia pestis, which causes bubonic and pneumonic plagues and is considered a potential bioterrorism agent. Bubonic plague, which is transmitted to humans primarily through bites from infected fleas, causes swollen lymph glands ("bubos"), while pneumonic plague, a highly contagious disease that is transmitted from person to person, primarily affects the airways. Both diseases can be rapidly fatal without antibiotic treatment.

Salama and Dr. Jeff Delrow, staff scientist and manager of the Genomics Shared Resource, will also co-direct one of the center's core laboratories which will develop tools for genomic analyses to be used by investigators affiliated with center. Salama said the biodefense center draws together the area's leading experts in bacterial infectious-diseases research to create a comprehensive infrastructure for vaccine development.

"The beauty of having a center of excellence is that you can bring numerous resources to bear on important scientific problems, which individual labs could never do on their own" she said. "In addition to developing vaccines for the bacteria we plan to focus on in the center, my hope is that the tools and strategies that we create can be applied to basic research and vaccine development for other infectious diseases."

The biodefense center's research initially will focus on the bacteria Yersinia pestis, Francisella tularensis and Burkholderia pseudomallei, all of which have been named as potential bioweapons because they are highly infectious.

Francisella tularensis causes tularemia, an animal disease that can be spread to humans through ticks that have fed on infected animals. The disease causes pneumonia-like symptoms and can be fatal without antibiotic treatment. Burkholderia pseudomallei causes meliodosis, a disease that infects both animals and man and may cause fever, muscle aches, skin lesions and death if antibiotic treatment is not initiated swiftly. In contrast to viral agents such as smallpox and Ebola virus, none of the biological agents to be studied requires the highest level of biosafety laboratory containment.

Salama will identify potential targets for vaccines against Yersinia using strategies she has developed in her laboratory to study the bacterium Helicobacter pylori, which can cause gastritis, stomach ulcers and gastric cancer. The approach involves identifying bacterial genes that become highly activated during the course of infection and that are required by the microbe to cause disease. Proteins that are produced by this subset of genes could then be purified and tested to see whether they trigger a protective immune response after injection into an animal, the principle behind preventive vaccines.

"The idea is to find proteins that are made in abundance by the bacteria when it infects an animal-which are the most likely proteins to provoke an immune response-but that also are absolutely necessary for the bacteria to cause illness," she said.

Gene identification

The work will use gene-scanning tools known as DNA microarrays, which permit scientists to measure the activity of all of a bacterium's genes at once. Salama and Delrow already have constructed microarrays, also known as gene chips, for Helicobacter pylori and will apply their expertise to develop analogous chips for the infectious bacteria to be studied by the biodefense center.

Once the highly active genes are identified, the researchers will sift through a pool of genetically manipulated Yersinia strains, each of which contains a mutation in a different gene, and choose those with mutations in the abundantly expressed genes to determine which strains have been rendered incapable of infection. Salama developed this approach in her laboratory to identify analogous genes in Helicobacter.

After the Yersinia project is well underway, Salama will use the approach to identify vaccine targets in other potential agents of bioterrorism, including Francisella tularensis. These and other basic-research studies conducted through the WWAMI center are expected to ultimately lead to new treatments and vaccines to protect the public through preventive medicine. The center will not engage in weapons-related research. The project also will help educate and train medical students, physicians and scientists in five states, and will provide clinical training at hundreds of sites.

For more information about the Regional Centers of Excellence, visit the NIAID Biodefense Web site at: http://www.niaid.nih.gov/biodefense/html.

Fred Hutchinson Cancer Research Center is a world leader in research to prevent, detect and treat cancer and other life-threatening diseases.