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Biological Sciences
Research Highlights

July 2009

Targeting Toxins

NIH funding will help PNNL scientists develop assays to combat bioterrorism

Several countries and extremist groups are believed to possess powerful biological weapons.  Terrorists with limited skills and resources are making biological weapons without much difficulty, and currently there are no adequate methods for immediate detection of toxins used for biological weapons agents.  Researchers from Pacific Northwest National Laboratory are attacking this problem by developing diagnostic assays to identify and differentiate toxins that could be used as bioterrorism agents.  Swift detection of these agents is crucial for minimizing their potentially catastrophic effects.   

The research team, with funding from the National Institutes of Health, is charged with providing a highly sensitive and specific assay for detecting biological weapon toxins by combining molecular recognition with enzymatic activity assays.  First, the researchers will develop an enzyme-linked immunosorbent assay (ELISA) microarray, which is a test for particular antigens or antibodies to detect botulinum neurotoxin (serotypes A through F), ricin toxin, shiga, and staphylococcal enterotoxin B.  They will then develop a toxin activity assay that is specific for these toxins.  Finally, they will integrate the ELISA microarray and the activity assay into a single platform. This will allow for the sensitive and specific detection of the toxins in clinical samples, which include sera, nasal swabs, and stool samples.

"Previous assays that have been developed have had limitations such as length of assay time and ethical concerns related to animal studies," said Dr. Susan Varnum, a senior research scientist at PNNL.  "Our assay avoids these limitations. Additionally, we're not only going to identify the toxins, but also study how they function.  This will lead to a better understanding of toxins.  We'll know which ones can really cause a scare and which ones not to be concerned about."            

Many of these toxins, such as botulinum neurotoxin and ricin, act at low concentrations and require highly sensitive assays for detection.  It is crucial to determine whether the toxins are active or inactive because molecular recognition assays (i.e., immunoassays) recognize surface features of proteins that may not be related to any enzymatic activity or other mechanism of toxicity.  Consequently, inactive protein toxins could give off false signals, leading to an overestimation of the threat. 

Varnum is the principal investigator for this 5-year, $1.25 million program. Her research team includes Cheryl Baird, Don Daly, Keith Miller, and David Wunschel.

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