Oak Ridge Associated Universities
Location
Duluth, MN | United States
Job description
Reference Code: EPA-ORD-CCTE-GLTED-2021-03
Applications may be reviewed on a rolling-basis and this posting could close before the deadline. EPA Office/Lab and Location: A research opportunity is available at the Environmental Protection Agency (EPA), Office of Research and Development (ORD), Center for Computational Toxicology and Exposure (CCTE), Great Lakes Toxicology & Ecology Division (GLTED) located in Duluth, Minnesota. Research Project: The US EPA is mandated to address the endocrine disrupting potential of thousands of chemicals. For the majority of these chemicals there is a lack of information regarding whether they have the potential to cause adverse effects from impacts on thyroid hormone status. Understanding the important targets within the network of processes involved in maintaining normal functioning thyroid hormone levels, and what approaches to best assess activity at those targets are critical to developing a comprehensive approach to evaluating thyroid hormone disrupting potential of large numbers of chemicals. Recently, a number of thyroid-related in vitro high-throughput screening (HTS) assays have been developed to broaden assay coverage for molecular targets potentially leading to thyroid disruption and were implemented to screen US EPAs ToxCast Phase 1, 2 and E1K libraries. This battery of thyroid-related in vitro HTS assays can be employed to rapidly assess potential chemical toxicity toward these targets. However, this screening approach leaves uncertainties regarding the meaning of in vitro activity data as it relates to in vivo outcomes. Part of this research effort aims to develop a translational process that integrates relevant information, models, and data streams to provide richer context to in vitro results related to thyroid disruption. To that end, targeted in vivo testing will be performed using a model amphibian species (Xenopus sp.) routinely used for testing thyroid disrupting chemicals, to understand whether, and how, in vitro activity of chemicals translates to in vivo outcomes. Additionally, this research will employ existing computational tools such as the octanol-water partition coefficient (logKow) and quantitative structure-activity relationships (QSAR) models to provide deeper interpretation of in vitro data and further prioritize chemicals most likely to impact thyroid function in aquatic systems. The translational principles demonstrated will have much broader applicability across ToxCast HTS assays and aquatic vertebrates. This research will provide translational context necessary for ecological risk assessment and deliver timely information relative to PFAS thyroid toxicity. Coordinated efforts will be undertaken in the mammalian model in parallel to these efforts to bolster cross-species concordance of modes of action and adverse outcome pathways (AOPs) related to thyroid disruption. Under the guidance of a mentor, the participant may be involved in the following training activities: Applying innovative and cutting-edge approaches in in vitro to in vivo extrapolation and reverse toxicokinetics to translate effect concentrations measured in multi-well plates to equivalent blood, tissue, or environmental media concentrations. Designing workflows and applying data analysis pipelines for automated and standardized analysis of large data sets. Developing and implementing a data archiving and storage system. Identifying statistical and performance-based measures of assay and data quality and implementing quality assurance and quality control. Using analytical chemistry methods to verify chemical concentrations, purity, and availability/partitioning in the test vessels. Compiling and synthesizing data from the peer-reviewed literature and on-line data sources and organizing it according to the AOP framework in order to aid interpretation of test results. Presenting research results at regional, national, and/or international conferences and workshops. Contributing to the preparation of peer-reviewed journal articles and disseminating research results to project partners and stakeholders. Conducting field-based research outdoors and/or at remote laboratory locations other than the primary training location. Learning Objectives: The participant will be integrated into a transdisciplinary research team and engaged in multiple aspects of project planning, communication and coordination, research implementation, and analysis. The participant will have the opportunity to interact with internationally recognized leaders, both within and outside EPA. The participant may contribute to and/or publish original research. The participant will learn a diversity of laboratory, analytical, and computational techniques which can be applied across life sciences research fields. The research participant will learn to operate and use a range of scientific equipment. The participants will learn to evaluate data quality, trouble shoot research results, apply statistical methods for data analysis and interpretation. Anticipated Appointment Start Date: Spring 2021. All start dates are flexible and vary depending on numerous factors. Click here for detailed information about start dates. 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