Environmental, Microbial and Mammalian Biomolecular Responses to AhR Ligands

点击翻译按钮获取中文摘要

OVERALL CENTER SUMMARY/ABSTRACT Support is requested to continue human health-oriented research on risks from exposure to chemicals commonly found in Superfund sites and on remediation technologies to minimize exposure to chemicals from those sites. The pollutants under investigation belong to the halogenated aromatic hydrocarbon family that bind and activate the aryl hydrocarbon receptor (AhR). These chemicals, which include polychlorinated dibenzo-p-dioxins, dibenzofurans, biphenyls and polyaromatic hydrocarbons, are environmentally persistent, lipid soluble contaminants that bioaccumulate in the food chain leading to human and wildlife exposure. A highly integrated, multidisciplinary research program is proposed consisting of five research projects and five supporting cores. The research team includes 25 investigators from Michigan State University (20), Emory University (1), Purdue University (1), Rutgers University (2) and the Michigan Department of Health and Human Services (1). The central overarching theme of the proposed program is to define specific aspects of environmental, microbial and mammalian biomolecular responses to environmental contaminants that act as agonists for the AhR. The major research thrusts will provide new mechanistic information regarding: (1) the diversity and physiogenomic responses of (chloro)dioxin degrading microbial populations indigenous to soils, sediments and groundwater; (2) the geochemical parameters governing adsorbtion, bioavailability and long-term fate of AhR ligands through interactions with geosorbent compositions in soils and sediment components; and (3) the mechanisms of action and computational modeling of interactions between specific biochemical pathways and ligand-activated AhR associated with the liver, thyroid and immune system responses. The Computational Modeling Core (CMC) will develop dynamic computational models of biological responses induced by AhR ligands. An Administrative Core will support research, training, community engagement, data management, and information and technology transfer in this Superfund Research Center (SRC). Within the Administrative Core, research translation will disseminate research findings to target audiences in government, industry and academia. A Community Engagement Core (CEC) will communicate with community stakeholders through engagement with county and city health officials in three new Michigan communities that continue to experience dioxin exposure. A Data Management and Analysis Core will provide the technology, expertise, infrastructure and training necessary to curate datasets, metadata, processing and analyses needed to properly manage and share high quality reproducible data. Lastly, a Research Experience and Training Coordination Core (RETCC) will ensure cross-disciplinary training to pre- and postdoctoral trainees.