Continuing development of new pesticides is a necessity given the growing problem of pest resistance and the need to satisfy environmental and health concerns. Biorational approaches to insecticide discovery incorporate a knowledge of insect biochemistry and physiology in the identification of compounds acting on specific insect molecules. Anthos is a company designing assays to screen natural products or synthetic compounds for substances with insecticidal properties employing cloned insect membrane receptors as standard reaction components. This proposal describes the cloning and expression of the receptor for an insect neurotransmitter. Once obtained, the recombinant molecule can be employed in receptor-based screens to identify potential insecticidal compounds. Depending on the exact screening conditions, these substances may act as broad spectrum pesticides or behave in a more specific manner. Emphasis on insecticides that affect insectspecific targets insures the development of safer products.Applications:Successful completion of this Phase I and a Phase II research program will result in the development of an insect receptor-specific insecticide screening assay and in the discovery of novel compounds with insecticidal activity and reduced vertebrate toxicity. In this case, the target for new insecticide discovery is HelicoverDa zea. a devastating secondary pest of cotton. ~, zea is estimated (with the related species, Heliothis virescensl to be the target of half of the tonnage of insecticides used annually. Considering that the U.S. market for insecticides was over Sl billion in 1989, a new, effective, and non-toxic L zea insecticide is a significant commercial opportunity.