Over one billion people worldwide are infected by parasitic nematodes that cause a variety of debilitating nutritional, gastrointestinal, and other diseases. Many such infections are not curable with existing medications, and preventive vaccines are not yet feasible for these complex parasites. The goal of this project is to develop novel screens for safe anti-nematode compounds that will fulfill this human health need. The results of Phase I demonstrated that a key element of nematode parasitism is recapitulated in an easily grown and well studied model nematode, Caenorhabditis elegans. Phase II will exploit the unique adaptability of C. elegans for miniaturized liquid-based handling in the development of a high throughput screen, which will be utilized to identify compounds with the ability to interfere with this aspect of nematode biology. Secondary in vitro assays on selected parasitic nematodes will be used to select those active compounds that are most promising for further evaluation in animal models of parasitism in Phase III. This approach holds great promise for developing safe and selective anti-nematode drugs.
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