Department Environmental Toxicology

Adverse outcome pathways (AOPs) infer cause-effect relationships between stressors and adverse outcomes in organisms. An AOP consists of an adverse outcome (AO), a molecular initiating event (MIE) representing the first trigger towards an AO, and key events (KEs) representing the steps between the MIE and AO. ⁠ However, while AOPs could help describe the plethora of potential effects that chemicals may have on ecosystems, the number of existing AOPs is small (<500 as of May 2024), cover few species and chemicals, and traditional methods for AOP development are slow.

A growing concept in AOPs is that complete mechanistic descriptions from the molecular level up to the cellular and tissue level are unnecessary in many applications, and that simplifying AOPs could help increase the rate of acceptance for regulatory contexts. For this project, we will use data integration and network analysis to computationally predict AOPs for aquatic organisms. As a starting point, this project will focus on neurotoxicity and endocrine disruption for zebrafish, roundworms, and clawed frogs. We will develop a data integration protocol to build AOP networks and extract candidate AOPs for each species. Then, we will use these candidate AOPs to assess similarities and differences in toxicity mechanisms across species and determine the potential for these new AOPs to fill knowledge gaps