Integrating behavioral and molecular classifiers towards mechanistic understanding of toxicity of environmentally persistent pharmaceutical pollutants
Supervisor: Prof. Steven Husson
Background Pharmaceuticals are widely used by humans, for food production or for veterinary purposes, but they may also enter and persist in the environment. Environmental persistent pharmaceutical pollutants (EPPPs) comprise one of the few classes of chemical pollutants that were specifically designed to act on living cells. Not only effects on human health should be considered, but also effects on the environment in general, with special attention to aquatic organisms. However, few studies on the responses of fish to residues of pharmaceuticals have been performed and very few on variables that are plausibly linked to any (therapeutic) mode-of-action.
Methods We will use a 3D video tracking platform to study zebrafish behavior after exposure to defined EPPPs. Different parameters will be extracted and we next aim to define behavioral classifiers by cluster analysis. In the future, we want to correlate behavioral parameters with molecular changes obtained from differential proteomics (and transcriptomics) datasets to obtain mechanistic and functional insights underlying aversive effects.
Significance As the zebrafish is an important vertebrate model in neuroscience and in ecotoxicological research, our results will be of toxicological and biomedical relevance. In addition, physiological, behavioral and molecular changes (fingerprints) may be attributed as early warning systems of disturbance at higher levels of organization.