Fish are a crucial group of organisms that inhabit diverse ecosystems, contributing vital services while being sensitive to various stressors, including chemical pollution. They often bioaccumulate chemicals and are essential in labs for environmental risk assessment. However, laboratory animal testing is ethically contentious, resource-intensive, and a major bottleneck in chemical risk assessment.

In our research on fish and fish cell lines, we have discovered that reduced cell proliferation and/or increased cell death in vitro is associated with inhibited growth after chemical exposure. Conversely, chemical exposure that doesn’t hinder fish growth also doesn’t reduce cell count in vitro. The question remains: how do chemicals with diverse structures and mechanisms of action result in the same outcome – reduced cell population and thus, hindered fish growth?

The ecotoxicology community has yet to find a molecular, mechanistic answer. Our research project aims to uncover the molecular response networks activated in fish cells upon chemical exposure, leading to reduced cell population growth. We will achieve this through cell-based chemical exposure experiments, cutting-edge cellular assays like “cell painting”, genome-wide gene expression measurements, bioinformatics and network-based analyses, and validation of in vitro findings in an in vivo system. This advancement will accelerate and economize chemical risk assessment by decreasing reliance on in vivo animal testing.

WP1 – experiments to determine the optimum chemical concentrations and time points for sampling, and the chemical exposure experiments. WP2 – develop the cell-based morphological and functional profiling assays, and measurements based on the experimental design from WP1. WP3 – based on a systemic literature and database review we will develop causal molecular networks that lead to a decrease of fish cell population growth. WP4 – develop the analysis pipelines and perform the analysis of the transcriptomics, translatomics and the phenotypic profiling data obtained from WP1 and WP2. Identification of the molecular pathways and biomarkers behind the decrease in cell population growth, and integrating the experimental data with the WP3 networks will allow quantitative prediction of the toxicity response. WP5 – in vivo conformation of WP4. WP6 – project and data management, and dissemination.