Researchers in Aroian's laboratory discovered several years ago that the roundworm C. elegans and other nematodes can be killed or made seriously ill by a pore-forming toxin known as Cry5B. That toxin is produced by Bacillus thuringiensis, the bacterium commonly known as Bt, which is used by organic farmers as a natural pesticide to control insect pests on crops. Although Cry5B can't hurt humans because the toxin doesn't recognize human cells, it hurts worms in a manner similar to the pore-forming toxins that affect humans.
Aroian and his student discovered that when C. elegans is exposed to either a low dose of Cry5B toxin for a long period of time or a high dose of the toxin for a short period of time, as might occur in nature, the roundworms recover and continue to survive. Recognizing that this natural defense mechanism to a pore-forming toxin could have application to human bacterial infections, Aroian and Danielle Huffman, a graduate student in his laboratory and the first author of the research paper, set about to determine the biochemical and genetic mechanisms that allowed the worms to do this.
Huffman and Roman Sasik, a postdoctoral fellow working with Jacques Corbeil at UCSD's medical school, developed a way to determine which roundworm genes were activated when they came into contact with the pore-forming Cry5B toxin and an equivalent dose of cadmium, a toxic heavy metal. Some of the genes activated by one toxin were activated by the other, but the scientists found that some were not, including two that were known to play important and general roles in immunity in humans. However, these genes had never been
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Contact: Kim McDonald
kmcdonald@ucsd.edu
858-534-7572
University of California - San Diego
12-Jul-2004