GENE DIVERGENCE OF ARYL HYDROCARBON RECEPTORS (AHR) IN EARLY VERTEBRATES

早期脊椎动物芳基烃受体（AHR）的基因分歧

• 批准号: 8360076
• 负责人: REBEKA RAND MERSON
• 金额: $ 6.61万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360076
• 关键词: AHR gene; Agonist; Aryl Hydrocarbon Receptor; Behavioral Research; Biomedical Research; Cell physiology; Dioxins; Embryonic Development; Environmental Health; Enzymes; Exposure to; Funding; Gene Targeting; Genes; Grant; Health; Human; Location; Marines; Mediating; Metabolic Biotransformation; National Center for Research Resources; Pathway interactions; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Role; Shark; Source; Students; Testing; United States National Institutes of Health; Vertebrates; aryl hydrocarbon receptor ligand; aryl hydrocarbons; comparative genomics; cost; egg; paralogous gene; protein function; receptor; receptor expression; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Adverse health effects from exposure to dioxin-like compounds are in part mediated through activation of aryl hydrocarbon receptors (AHR), expression of genes encoding biotransformation enzymes, and dysregulation of numerous genes outside the toxic response pathway. AHR proteins have non-transcriptional roles in cell physiology in the absence and presence of AHR ligands. Thus, it is difficult to distinguish AHR-dependent toxic response mechanisms from the perturbation of endogenous function of AHR. We study the divergence of function among multiple AHR paralogs in early vertebrates so we may separately test the pleiotropic functions of the single mammalian AHR. Our previous studies demonstrate that each product of the AHR gene both overlap and diverge in subcellular location and function. In the current study, undergraduate student projects aim to assess the function of shark AHRs in cellular processes, embryonic development of egg-laying marine vertebrates, and to investigate the relationships of these early vertebrate AHR genes with those of primates using comparative genomics. We aim to develop an effective paradigm to separately test hypotheses about subsets of mammalian AHR gene targets and non-transcriptional AHR protein function. Results from our research will provide information relevant to human responses to environmental AHR agonist exposure, and the relationship between environmental health and embryonic development.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 暴露于二恶英化合物的不良健康影响部分是通过激活芳基烃受体（AHR），编码生物转化酶的基因的表达以及在毒性反应途径以外的许多基因失调的基因的表达而介导的。在不存在AHR配体的情况下，AHR蛋白在细胞生理中具有非转录作用。因此，很难将依赖AHR的毒性反应机制与AHR内源性功能的扰动区分开。我们研究了早期脊椎动物中多个AHR旁系同源物之间功能的差异，因此我们可以单独测试单个哺乳动物AHR的多效性功能。我们以前的研究表明，AHR基因的每个产物在亚细胞位置和功能中均重叠和分歧。在当前的研究中，本科生的项目旨在评估鲨鱼AHR在细胞过程中的功能，卵形海洋脊椎动物的胚胎发育，并研究使用比较基因组学的这些早期脊椎动物AHR基因与灵长类动物的关系。我们旨在开发有效的范式，以分别检验有关哺乳动物AHR基因靶标和非转录AHR蛋白功能的亚集的假设。我们研究的结果将提供与人类对环境AHR激动剂暴露的反应有关的信息，以及环境健康与胚胎发展之间的关系。