Environmental, Microbial and Mammalian Biomolecular Responses to AhR Ligands

总体中心总结/摘要 要求提供支持，以继续就接触化学品的风险开展面向人类健康的研究 通常在超级基金场地和补救技术中发现，以尽量减少接触化学品， 这些网站。受调查的污染物属于卤代芳烃家族， 结合并激活芳烃受体（AhR）。这些化学品，其中包括多氯 二苯并对二恶英、二苯并呋喃、联苯和多环芳烃具有环境持久性， 脂溶性污染物在食物链中生物累积，导致人类和野生动物接触。一 高度集成的，多学科的研究计划，建议由五个研究项目和五个 支持核心。研究小组包括来自密歇根州立大学（20）、埃默里大学（20）的25名研究人员 大学（1），普渡大学（1），罗格斯大学（2）和密歇根州卫生部和 人类服务（1）。拟议方案的中心主题是确定具体的 环境、微生物和哺乳动物生物分子对环境的反应 作为AhR激动剂的污染物。主要的研究重点将提供新的机制， 信息：（1）（氯）二恶英降解微生物的多样性和生理基因组学反应 土壤、沉积物和地下水中的土著种群;（2）控制 AhR配体通过与地质吸附剂组合物相互作用的吸附、生物利用度和长期命运 在土壤和沉积物成分;和（3）的作用机制和计算模型， 特异性生化途径和与肝脏、甲状腺相关的配体激活AhR之间的相互作用 和免疫系统反应。计算建模核心（CMC）将开发动态计算 AhR配体诱导的生物反应模型。一个行政核心将支持研究、培训、 社区参与、数据管理以及信息和技术转移 研究中心（SRC）。在行政核心内，研究翻译将传播研究成果 向政府、工业界和学术界的目标受众提供调查结果。社区参与核心（CEC） 将通过与县和市卫生官员的接触与社区利益相关者进行沟通， 三个新的密歇根州社区继续经历二恶英暴露。数据管理和 分析核心将提供管理数据集所需的技术、专业知识、基础设施和培训， 适当管理和共享高质量可复制数据所需的元数据、处理和分析。 最后，研究经验和培训协调核心（RETCC）将确保跨学科培训 博士前和博士后实习生。

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.