Goal 1: to identify unique protein and metabolite expression patterns in blood plasma specific to individual environmental stressors that are linked to higher level adverse outcomes

In this project, we will characterize groups of plasma proteins and metabolites that exhibit unique molecular expression patterns (MEPs) during molecular initiating and key events so that they can be specifically linked to a particular environmental stressor and an environmental adverse outcome pathway (AOP). These plasma MEPs could then be used as a diagnostic tool to identify exposure to environmental stressors (i.e., contamination, harmful algal blooms, or nutrient limitation) and for monitoring early events that could be detected before full-scale population and ecological level events have occurred (analogous to the canary in the coal mine). An MEP might also be identified to gain a mechanistic understanding for a contaminant of emerging concern that is less characterized in order to identify potential environmental impacts and aid in the establishment of novel adverse outcome pathways. We are interested in testing the effects of per- & polyfluoroalkyl substances (PFAS), cyanotoxins, chromate, fibrate pharmaceuticals, and illicit drugs.

Goal 2: to expand our knowledge of blood plasma function in vertebrate fish by determining the phenotypic plasticity of protein and metabolite abundance in plasma

To achieve this objective, the research program will determine to what extent different types of molecules (i.e., nuclear receptors, enzymes, hormones, or structural molecules) are represented in blood plasma and, if possible, from where (i.e., what tissues, organs, or organ systems) those molecules originate. For instance, classes of proteins that are more likely to increase or decrease in concentration when specific organ systems or signaling pathways become challenged by environmental factors will be identified, along with temporal variation and the dynamic range of that response. Other complicating factors will be considered as well, such as how those proteins differ between vertebrate sexes, or under different dietary conditions, and at varying stages of physiological development. This information will determine baseline variation typical of “normal” physiology and will be used to help eliminate the inclusion of false positive molecules from the MEPs determined in project 1; thus, all studies within Dr. Simmons’ research program will be designed to address projects 1 and 2 concurrently.

Goal 3: to develop an online database containing MEPs specific to environmental stress and indicative of adverse outcomes

The MEPs determined in the above research projects will be of limited use to society if they are not disseminated and promoted widely for use in environmental monitoring and protection. To address this, This database would be widely accessed by government, academic, and not-for-profit scientists. Initially, the database will be built and developed using MEPs generated by our research group; however, it will be expanded by users from the ecotoxicology research community who will be able to upload their own validated MEPs. All entries will be linked to other relevant online information, such as the AOP wiki, the PRIDE Archive, PubChemUniProt, and the comparative toxicogenomics database and will automatically call relevant ecotoxicological information where available.