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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 接触二恶英类化合物对健康的不良影响部分是通过激活芳香烃受体(AHR)、编码生物转化酶的基因表达以及毒性反应途径以外的许多基因的失调来调节的。在AHR配体缺失和存在的情况下，AHR蛋白在细胞生理学中具有非转录作用。因此，很难区分AHR依赖的毒性反应机制和AHR内源性功能的扰动。我们研究了早期脊椎动物多个AHR同系物之间的功能差异，从而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上既有重叠又有分歧。在目前的研究中，本科生项目旨在评估鲨鱼AHR在细胞过程、产卵海洋脊椎动物胚胎发育中的功能，并利用比较基因组学研究这些早期脊椎动物AHR基因与灵长类AHR基因的关系。我们的目标是开发一种有效的范例来分别测试关于哺乳动物AHR基因靶标亚群和非转录AHR蛋白功能的假设。我们的研究结果将提供与人类对环境AHR激动剂暴露的反应相关的信息，以及环境健康和胚胎发育之间的关系。