Investigating chemical pollutants at the ‘druggable’ GPCRome: a nexus of pollutant toxicity and predictive risk assessment

In modern society, synthetic chemicals are manufactured by the ton for their use in industrial processes and commercial products. These anthropogenic (i.e., man-made) chemicals are applied for various purposes, such as the pesticides sprayed on crops, the coatings on nonstick pans, and the plastic of water bottles. The widespread use of chemicals in this fashion inevitably results in their exposure to humans. Once inside our body, some of these chemicals are known to impact biological processes that are critical in maintaining our health.

Among the thousands of chemicals manufactured, many are particularly toxic to humans. Substantial evidence has linked human exposure to chemical pollutants to harmful outcomes, including cancer, obesity, and brain defects. Therefore, it is critical that we properly investigate chemical pollutants and identify their potential threat before they result in broad harm to our health. In this work, we help with these efforts.

Here, we apply techniques used to discover the biological activity of drugs as an entirely new approach to investigating chemical pollutants. This approach uses hundreds of human receptors that are heavily involved in the everyday signaling and balance of our biological activity. By testing chemical pollutants for their activity at these receptors, we are provided a ‘snapshot’ of their biological activity. This information can then be used to deduce the broad effects of chemicals within our bodies and predict their potential toxic outcomes. This approach is advantageous because it can be used to assess large numbers of chemicals against hundreds of different receptors - each connected to a unique biological function. In this work, we show the utility of our approach by completing a pilot screen that results in newly discovered activity for notorious chemical pollutants.