Infections by roundworm parasites, called nematodes, result in human mortality and morbidity, especially in subtropical and tropical regions of Africa, Asia, and the Americas. The World Health Organization estimates 2.9 billion people are infected. There are 595 known nematode parasites of vertebrates including hundreds that infect domesticated animals. Widespread use of drugs to control parasites over several decades has led to the evolution of drug-resistant forms of several nematode parasites. The rewards for the development of a new anthelmintic class are substantial. In phase II of our research, we aim to identify -100 genes that are essential to the model nematode Caenorhabditis elegans. We will then clone homologs of these genes from a range of free-living and parasitic nematodes. Using RNAi technology on the free-living nematodes, we will determine which homologs are essential to the nematode lifecycle. Genes that prove essential to all the nematodes tested will be designated as potential nematicide targets. In collaboration with academic laboratories, we will use RNAi to validate target genes in parasitic nematodes. We will test potential inhibitors of the most promising target genes because such compounds could lead to new anti-nematode therapies.
