On Sept. 14, 2004, Pacific Northwest National Laboratory (PNNL) announced it had received a $10.3 million biodefense contract from the National Institute of Allergies and Infectious Agents (NIAID) to identify the proteins that regulate the bacteria that cause salmonella poisoning and typhoid fever, and the mpox virus.

The five-year award was the Department of Energy lab’s third $10 million National Institutes of Health grant or contract in the past year and the second for Richard D. Smith, principal investigator and a Battelle Fellow at PNNL.

Besides mpox, which serves as a close viral analog to deadly smallpox, two species from the genus Salmonella will be examined: typhimurium (which causes food poisoning) and typhi (typhoid fever). These pathogens, which spread quickly and are not easily combated with conventional drugs, could lead to major epidemics if enlisted by terrorists. NIAID is banking that determining which microbial proteins interact with which human host cells will point drug designers toward quick and effective treatments during an outbreak.

To conduct the analysis of these microbial proteins, scientists at PNNL used proteomics instruments and approaches unavailable elsewhere that simultaneously combine the high-resolution separation of proteins with their identification, on a suite of powerful mass spectrometers developed at the W.R. Wiley Environmental Molecular Science Laboratory on the PNNL campus.

Collaborators at Oregon Health Sciences University in Portland prepared the infectious agents for the proteomics at PNNL and assisted in analyzing the data generated there. The OHSU group was able to knock out key genes that regulate the degree of pathogenic activity in the microbes. This capability allowed researchers to test proteins identified at PNNL as candidates to be targeted by drugs.