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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

基本信息

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
项目类别：
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

项目摘要

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.

整体中心摘要/摘要