Phenotypic screening, now in vogue in the pharmaceutical industry, has always been a major discovery approach for agrochemicals. However we have not exploited a wide variety of phenotypes � death being by far the most common phenotype used in the discovery of insecticides and nematicides. Here we describe a novel phenotypic screening approach in the nematode C. elegans. Previous work has demonstrated that the spiroindoline insecticides induce a characteristic phenotype or symptom in C. elegans. Spiroindolines are insecticidal and affect cholinergic signaling in both insects and nematodes. We reasoned that if we screened for molecules that induced the spiroindoline phenotype we might discover new modulators of acetylcholine signaling which may, in turn, be useful starting points in insecticidal discovery. We describe a pilot screen of 6000 compounds from which we identified one that induced the spiroindoline phenotype. By our reasoning, this compound putatively interacts with acetylcholine signaling. To test this we show that the compound genetically interacts with acetylcholine signaling which is consistent with a protein target within this system. We conclude that this approach can identify molecules affecting cholinergic signaling.

Phenotypic screening in agrochemical discovery

248th National Meeting (2014)

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