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: 8167612
• 负责人: REBEKA RAND MERSON
• 金额: $ 8.15万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167612
• 关键词: AHR gene; Agonist; Aryl Hydrocarbon Receptor; Cell physiology; Computer Retrieval of Information on Scientific Projects Database; Development; Dioxins; Environmental Health; Enzymes; Exposure to; Funding; Gene Targeting; Genes; Genomics; Grant; Health; Human; Institution; Libraries; Mediating; Metabolic Biotransformation; Pathway interactions; Physiology; Research; Research Personnel; Resources; Role; Shark; Source; Students; Testing; United States National Institutes of Health; Vertebrates; aryl hydrocarbon receptor ligand; design; gene induction; paralogous gene; protein function; receptor; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adverse health effects from exposure to dioxin-like compounds are in part mediated through activation of aryl hydrocarbon receptors (AHR), induction of genes encoding biotransformation enzymes, and dyregulation 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 support that shark AHR paralogs diverge in function. In the current study, several undergraduate student projects are designed to assess the function of shark receptors in cell physiology, development, and toxic responses to AHR agonists, and to investigate the genomic context of these early vertebrate AHR genes with a BAC library. 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 physiology, development, and environmental health.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 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诱导以及在毒性反应途径以外的许多基因的染色体来介导的。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。我们以前的研究支持鲨鱼AHR旁系同源物在功能方面有所不同。在当前的研究中，旨在评估鲨鱼受体在细胞生理，发育和对AHR激动剂的有毒反应中的功能，并研究这些早期脊椎动物AHR基因的基因组环境。 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生理，发展和环境健康有关的信息。