PT - JOURNAL ARTICLE AU - Anders Eriksson AU - Prachi Anand AU - Juliette Gorson AU - Corina Grijuc AU - Elina Hadelia AU - James C Stewart AU - Mandё Holford AU - Adam Claridge-Chang TI - Using <em>Drosophila</em> behavioral assays to characterize terebrid venom-peptide bioactivity AID - 10.1101/391177 DP - 2018 Jan 01 TA - bioRxiv PG - 391177 4099 - http://biorxiv.org/content/early/2018/08/13/391177.short 4100 - http://biorxiv.org/content/early/2018/08/13/391177.full AB - The number of newly discovered peptides from the transcriptomes and proteomes of animal venom arsenals is rapidly increasing, resulting in an abundance of uncharacterized peptides. There is a pressing need for a systematic, cost effective, and scalable approach to identify physiological effects of venom peptides. To address this discovery-to-function gap, we developed a sequence driven:activity-based hybrid approach for screening venom peptides that is amenable to large-venom peptide libraries with minimal amounts of peptide. Using this approach, we characterized the physiological and behavioral phenotypes of two peptides from the venom of predatory terebrid marine snails, teretoxins Tv1 from Terebra variegata and Tsu1.1 from Terebra subulata. Our results indicate that Tv1 and Tsu1.1 have distinct bioactivity. Tv1 (100 μM) had an antinociceptive effect in adult Drosophila using a thermal nociception assay to measure heat avoidance. Alternatively, Tsu1.1 (100 μM) increased food intake. These findings describe the first functional bioactivity of terebrid venom peptides in relation to pain and diet and indicate that Tv1 and Tsu1.1 may, respectively, act as antinociceptive and orexigenic agents. Tv1 and Tsu1.1 are distinct from previously identified venom peptides, expanding the toolkit of peptides that can potentially be used to investigate the physiological mechanisms of pain and diet.