Over one billion people worldwide are affected by parasitic nematodes that cause various debilitating nutritional, gastrointestinal, and other diseases. Many such infections are not curable with existing medications and preventative vaccines are not yet feasible for these complex parasites. Our goal is to develop novel screens for safe anti-nematode compounds that will fulfill this human health need. Our approach is first to show that a key element of nematode Caenorhabditis elegans, and then to design high throughput compound screens that exploit the unique adaptability of C. elegans for miniaturized liquid-based handling This approach holds great promise for developing safe and selective anti-nematode drugs.
This Phase I plan will establish the foundation for using the model nematode C. elegans to study expression and secretion of proteins important in nematode parasitism. Our results will direct the Phase II develoment of high-throughput screens for compounds that block parasitism by inhibiting the function of these proteins. Such chemicals will be developed as anti-nematode drugs for unmet needs in human health. The screening technology pioneered here will also be applicable to chemical discovery programs that target other aspects of parasitic nematode biology.