1) We will parameterize dynamic energy budget (DEB) models for one of the focal organisms in the project, the waterflea Daphnia magna. Two DEB model approaches will be used: “DEBkiss”, increasingly used in many current ecotoxicological studies, and DEBlipid, a variant developed in my group. Information from our previous, extensive, data synthesis on Daphnia bioenergetics, published in 2015, will be used along with recent data from Dr. Louise Stevenson (Oak Ridge National Lab) to inform likely ranges for parameters and will also provide priors for Bayesian methodology will enable us to leverage the large body of previously published data in interpreting new results from Dr. Stevenson’s lab.
2) We will calibrate DEB models for the second focal organism, fathead minnow (FHM) Pimephales promelas, emphasizing data on growth, development and reproduction. We will parametrize our two models for this species starting from data synthesized by a group at the National Institute for Mathematical and Biological Synthesis (NIMBioS) co-chaired by Nisbet and Dr. Murphy.
3) In collaboration with bioinformatics experts working with Dr. Murphy, we will use the transcriptomic data to identify the molecular networks underpinning PFAS mixture and PFOS exposure in the context of measured endpoints and information on available molecular interactions derived from protein modelling. We will attempt to connect enriched pathways with physiological modes of action in the DEB model following methodology from the NIMBioS group. The data from the various treatments will then be refit to the DEB models using the added information.