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Drug screening and delivery using C.elegans as a versatile platform

Despite being a premier model organism for studying basic biological processes such as programmed cell death and aging, C. elegans has not been utilized as an animal model for therapeutic drug screens and for pharmacological and toxicology studies.  One major reason is that there is no reliable and established method for delivering chemicals or compounds into C. elegans, especially hydrophobic chemicals or molecules, which often display interesting and potent pharmacological activities.  Recently we developed a simple and reliable method to expose C. elegans to water-insoluble chemicals using a non-toxic oil solvent spread onto worm culture plates. Using this method, we successfully identified two hydrophobic chemicals (naphthalene and para-dichlorobenzene) and several other compounds that inhibit C. elegans apoptosis in a concentration-dependent manner and thus established the validity of this method as a drug delivery protocol for C. elegans.  This method will allow screening of all sorts of drugs or compounds in C. elegans (it is easy to deliver water-soluble compounds to C. elegans since worms can grow in liquid cultures) and make C. elegans an ideal and inexpensive animal model for disease study and compound screens.  In particular, due to the short generation time of C. elegans (2.5 days per generation), we can complete a drug screen in a few weeks compared with a few years when using rodent models.  We are now in the process of doing large-scale screens in C. elegans for compounds that induce apoptosis or chemicals that inhibit necrosis.

Related publications

Yang, C.L., Yan, N., Parrish, J., Wang, X.C., Shi, Y.G., and Xue, D. (2006). RNA aptamers targeting the cell death inhibitor CED-9 induce cell killing in C. elegans. Journal of Biological Chemistry 281, 9137-9144. ( and )

Kokel, D., Li, Y.H., Qin, J., and Xue, D. (2006). The non-genotoxic carcinogens naphthalene and para-dichlorobenzene suppress apoptosis in C. elegans. Nature Chemical Biology 2, 338-345. ( and ). News in , , , , , , 

Kokel, D. and Xue, D. (2006). A class of benzenoid chemicals suppresses apoptosis in C. elegans. ChemBioChem 7, 2010-2015. ( and )

Zheng, L.J., Wu, X.Q., Li, S.S., Liu, B., and Xue, D. (2019). Cathepsin B inhibitors block multiple radiation-induced side effects in C. elegans. Cell Research 29, 1042-1045 (PDF)

Zhang, H., Zhu, Y., Suehiro, Y., Mitani, S., and Xue, D. (2023). AMPK-FOXO-IP3R signaling pathway mediates neurological and developmental defects caused by mitochondrial DNA mutations. Proc. Natl. Acad. Sci. USA 120: e2302490120 ( and ).