Eriksson, A., Anand, P., Gorson, J. et al. Using Drosophila behavioral assays to characterize terebrid venom-peptide bioactivity. Sci Rep 8, 15276 (2018). https://doi.org/10.1038/s41598-018-33215-2
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.
This work received major support for A.E. from A*STAR Joint Council Office grant 1231AFG030 awarded to A.C.C. The authors were supported by a Biomedical Research Council block grant to the IMCB. A.C.C. received support from Duke-NUS Medical School, Joint Council Office grant 1431AFG120 and Ministry of Education grant MOE-2013-T2-2-054. M.H. acknowledges funding from the Camille and Henry Dreyfus Teacher-Scholar Award, NSF awards CHE-1247550 and CHE-1228921, and a pilot award from Weill Cornell Medicine Clinical And Translational Science Center NIH-National Center For Advancing Translational Sciences grant (1UL1TR002384-01). Support for the Hunter-Belfer Bioinformatics Cluster was provided by the Center for Translational and Basic Research grant from the National Institute on Minority Health and Health Disparities (G12MD007599) and Weill Cornell Medicine—Clinical and Translational Science Center (2UL1TR000457-06).