University of Washington researchers will be taking part in a multi-site project examining a portion of the genome of the strain of influenza responsible for the "Spanish Flu" outbreak in 1918.

A group of researchers in the Department of Microbiology at the UW School of Medicine is teaming up with researchers from the Armed Forces Institute of Pathology and the Mount Sinai School of Medicine in New York to study the virus through a five-year, $12.7 million grant from the National Institutes of Health as well as Scripps Research Institute and the Centers for Disease Control.

The funding includes $300,000 this year to develop a proper bio-containment facility for studying the pathology of the virus. Work on the facility will begin after the NIH develops its guidelines for facilities handling flu strains.

The UW research team is led by Michael Katze, professor of microbiology.

"This allows us for the first time to combine genomics with pathology in animals and disease progression in studying the pandemic flu," Katze said. The pandemic flu struck in 1918-1919 and killed 40 to 50 million people, but we still know very little about why it was so lethal."

In addition to funding for studying the pathology of the virus, the NIH grant will also pay for animal model development, molecular biology and functional genomics research at the UW on this strain of influenza. Researchers hope to develop a molecular signature for different types of the virus using genomics. That signature could help scientists decipher the lethality of pandemic flu and other strains of influenza, Katze explained.

Perhaps most importantly, such work could also potentially be used as a diagnostic tool, or to test vaccines or anti-viral drug treatments for illness.

The proposed research will first occur on a small scale in the laboratory and will involve the use of non-human primates for in vivo studies. The researchers plan to use a vaccine strain of influenza to further refine their plans for biosafety and research methodologies. Before the next phase of research is done with segments of the 1918 genome, additional reviews and approvals will be needed, said Karen VanDusen, director of Environmental Health and Safety at UW.

"Everyone involved recognizes that there are many concerns and perceptions of risk," VanDusen said. "Future research will be conducted under bio-containment levels and with specific personal protective equipment that is over and above that which is necessitated by any risk identified. There's a nationwide understanding that we need to provide protection for the researchers now in the laboratory as they themselves seek to protect the world from a future pandemic."

By looking at specific gene products from the 1918 virus, isolating them, and working with them in a safer vaccine strain of flu, previously used in human studies, the University researchers hope to document how the original 1918 genomic components interact with the disease-fighting mechanisms in a host cell.

By better understanding the pathogenicity of the 1918 influenza virus at the systemic, cellular, and molecular levels, this significant research could eventually lead to effective medicines that could fight such infectious diseases, Katze said. This research is one example of the potential ability of researchers to answer important disease questions, long unsolvable, until the recent and successful sequencing of varied microbial and cellular genomes. Studies can now be safely conducted on genes and their components that were not possible in previous times due to these advances and progress in the genetic manipulation of viruses.

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