C. ELEGANS SCREEN FOR NOVEL ANTI-NEMATODE DRUGS

全世界有超过10亿人受到寄生线虫的影响，这些线虫会导致各种令人衰弱的营养、胃肠道和其他疾病。许多这样的感染并不是 对于这些复杂的寄生虫，用现有的药物和预防性疫苗是可以治愈的还不可行。我们的目标是开发安全的抗线虫化合物的新型筛选，以满足人类的健康需求。我们的方法首先证明了线虫的一个关键元素 利用线虫对小型化液体处理的独特适应性，设计高通量的复合筛网，为开发安全、选择性的抗线虫药物提供了广阔的前景。 建议的商业应用： 这项第一阶段计划将为使用线虫模型线虫奠定基础 研究线虫寄生中重要蛋白质的表达和分泌。我们的结果 将指导高通量筛分的第二阶段开发，用于阻止 通过抑制这些蛋白质的功能来寄生。这类化学品将发展为 人类健康中未得到满足的抗线虫药物。这项筛查技术开创了 这也将适用于以其他方面为目标的化学发现计划 寄生线虫生物学。

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. PROPOSED COMMERCIAL APPLICATION: 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.