This is a collaborative R21 application between Raffi Aroian of the Division of Biological Sciences at the University of California, San Diego (UCSD) and William Fenical of the Scripps Institution of Oceanography, UCSD. This program addresses the discovery and preclinical biological development of new anthelmintic drugs to treat the single largest class of neglected tropical diseases (NTDs), those caused by parasitic nematodes. The NTDs of focus in this application are trichuriasis and hookworm disease, although the results of this research are likely to apply more broadly, e.g., to Ascariasis, strongyloidiasis, lymphatic filariasis, and onchocerciasis. Currently, there are very few drugs (anthelmintics) available for these diseases that affect over 2 billion people and reports of greatly reduced efficacy are mounting. In general, the effort to develop new anthelmintic drugs has been drastically underfunded, which has led to a situation where the worldwide healthcare system is ill-prepared to prevent and deal with the development of resistance to the few drugs available. This program combines the extensive biological experience of the Aroian laboratory, with the chemical resources generated in more than 20 years of discovery-based marine microbiology research. A large collection of more than 15,000 strains of actinomycete bacteria, that have been cultivated, extracted and fractionated, now form the foundation of a collaborative program involving biological screening in numerous anthelmintic bioassays. In preliminary testing, several highly active fractions, apparently containing new chemical entities, have been discovered suggesting that an R21 pilot project is likely to lead to significant advances in anthelmintic drug discovery.