Developing high-throughput screens for nematocides

点击翻译按钮获取中文摘要

Livestock continue to be plagued by roundworm (nematode) parasites causing economic losses to Canadian farmers and ranchers. The best defense against these parasites are small molecule antiparasitic drugs (nematocides), several of which are on the market. However, parasites invariably acquire resistance to successful, and thus widely used drugs, limiting their efficacy. Anticipating the need for a new generation of nematocidal compounds, we have identified a family of neurotransmitter receptors that are unique to nematodes. The receptors are a family acetylcholine-gated chloride channels (ACCs). We have shown that a drug that activates the channels formed by at least one of the receptor proteins (ACC-1) should be lethal to worms. In the current proposal we seek to identify other lethal ACC receptors and develop an efficient method to screen large chemical libraries for compounds that activate the the ACCs. Such a lead compound would be developed into a safe deworming drug that would be less likely to suffer from resistance already developed against existing drugs.