High-content cell imaging for chemical toxicity screening in the model organism Caenorhabditis elegans

The use of animal models for screening environmental chemicals for toxicity is an important step towards determining potential hazards to humans. Due to the large number of environmental chemicals with unknown biological activity, high-throughput screening has served as the primary method in toxicity testing for the past decades. However, with the emergence of diverse cellular targets that have been shown to be adversely affected by chemicals, a transition towards high-throughput screening that incorporates high-content analysis provides an array of cutting-edge experimental advantages. Here, we utilized the genetic model organism Caenorhabditis elegans to demonstrate how high-content screening can be utilized to identify new chemical modifiers of RNA splicing with the U.S. ToxCast chemical library. Through this semi-automated workflow, we highlight areas where modern high-content screening platforms provide advantages that improves on traditional methodology in high-throughput screening assays to maximize quantitative and qualitative data types collected.