Environmental, Microbial and Mammalian Biomolecular Responses to AhR Ligands

AhR 配体的环境、微生物和哺乳动物生物分子反应

• 批准号: 10353530
• 负责人: Norbert E Kaminski
• 金额: $ 213.17万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10353530
• 关键词: Academia; Adsorption; Adverse effects; Affect; Agonist; Animal Model; Archives; Area; Aromatic Hydrocarbons; Aromatic Polycyclic Hydrocarbons; Aryl Hydrocarbon Receptor; Bacteria; Behavior; Binding; Biochemical Pathway; Biological; Biological Availability; Biological Models; Biomedical Engineering; Carbon; Chemicals; Cities; Cobalamin; Collaborations; Communities; Computer Models; County; Data; Data Analyses; Data Science; Data Set; Dioxins; Dose; Ensure; Environmental Engineering technology; Environmental Health; Environmental Pollution; Exposure to; Family; Food Chain; Future; Genetic Engineering; Goals; Government; Government Agencies; Health; Hepatic; Homeostasis; Human; Immune; Immune response; Industry; Information Technology; Interdisciplinary Study; Investigation; Investigator-Initiated Research; Knowledge; Learning; Ligands; Lipids; Liver; Mediating; Metabolic Biotransformation; Metadata; Methods; Michigan; Modeling; Molecular; Native-Born; Organ; Organism; Pathway interactions; Public Health; Reproducibility; Research; Research Personnel; Research Project Grants; Research Support; Research Training; Resources; Risk; Risk Assessment; Science; Scientist; Site; Soil; Superfund; Techniques; Technology; Technology Transfer; Tetrachlorodibenzodioxin; Thyroid Gland; Tissues; Toxic effect; Toxicant exposure; Training; Training and Infrastructure; Translational Research; United States Dept. of Health and Human Services; Universities; Work; advocacy organizations; aryl hydrocarbon receptor ligand; community based participatory research; community engagement; contaminated sediment; data management; dibenzo(1,4)dioxin; dibenzofuran; diphenyl; dosimetry; dynamic system; evidence base; experience; geochemistry; ground water; high dimensionality; human model; immune function; improved; microbial; microorganism; molecular modeling; next generation; novel; physiologically based pharmacokinetics; pollutant; programs; remediation; response; single-cell RNA sequencing; superfund site; tool

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.

总体中心摘要/摘要 要求支持继续以人类健康为导向的研究从暴露于化学物质的风险 通常在超级基金站点和补救技术中发现 那些网站。正在调查的污染物属于卤化芳基碳氢化合物家族 结合并激活芳基烃受体（AHR）。这些化学物质，包括多氯 Dibenzo-P-Dioxin，二苯并呋喃，双苯基和多芳烃在环境上是持久的 脂质可溶性污染物在食物链中产生生物蓄积的污染物，导致人类和野生动植物的暴露。一个 提出了高度综合的多学科研究计划，包括五个研究项目和五个 支撑芯。研究小组包括密歇根州立大学（20）的25名调查人员，Emory 大学（1），普渡大学（1），罗格斯大学（2）和密歇根州卫生部 人类服务（1）。拟议程序的主要主题是定义特定 环境，微生物和哺乳动物生物分子对环境的反应的方面 充当AHR激动剂的污染物。主要的研究推力将提供新的机制 有关：（1）（氯）二恶英降解微生物的多样性和生理基因组反应的信息 土壤，沉积物和地下水本土的种群； （2）管理的地球化学参数 AHR配体的吸附，生物利用度和长期命运通过与地质的组成相互作用 在土壤和沉积物成分中； （3）动作和计算建模的机制 特定的生化途径与肝甲状腺相关的配体激活的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。行政核心将支持研究，培训， 社区参与，数据管理以及此超级基金中的信息和技术转移 研究中心（SRC）。在行政核心内，研究翻译将传播研究 对政府，工业和学术界的目标受众的发现。社区参与核心（CEC） 将通过与县和城市卫生官员的互动与社区利益相关者沟通 三个新的密歇根州社区继续经历二恶英的暴露。数据管理和 分析核心将提供策划数据集所需的技术，专业知识，基础架构和培训， 元数据，处理和分析需要正确管理和共享高质量可重复的数据。 最后，研究经验和培训协调核心（RETCC）将确保跨学科培训 前和博士后学员。