IDENTIFICATION OF REGULATORY MOTIFS IN ABC GENES BY COMPARATIVE GENOMIC ANALYSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 项目1： ABC超家族是已知最大的蛋白质家族之一。ABCB和ABCC亚家族的成员在毒理学、药理学和疾病中发挥着重要的作用；然而，调节它们表达的机制还不是很清楚。该项目的目标是利用比较基因组学和基序寻找策略，在ABCB和ABCC基因的非编码区识别功能上有意义的调控基序。这项工作是与托尼·普兰查特博士(MDIBL，INBRE教员)和克莱尔·康登(USM，INBRE教员)合作完成的。 我还与PlanChart博士合作，进一步探讨了源自项目1的下列项目。 项目2：低剂量砷暴露对斑马鱼胚胎防御通路的干扰 在遗传、环境和人类疾病之间的相互作用中，接触化学品是一个风险因素。人类暴露在砷中的不良发育后果在很大程度上是未知的，尽管世界各地都有可能在子宫内暴露，而且研究结果表明存在令人担忧的原因(例如，癌症发病率增加、自然流产)。本研究旨在确定脊椎动物发育过程中低水平砷的靶向基因，以更好地了解砷毒性的机制。 项目3：确定与颅面发育有关的2，3，7，8-四氯二苯并对二恶英(TCDD)的新靶点 许多出生缺陷的病因涉及环境因素和调节重要生理过程的基因之间的相互作用。环境污染物2，3，7，8-四氯二苯并-对二恶英(TCDD)广泛存在于环境中，是一种已知的致癌致畸物质，但其毒性机制尚不清楚。这项研究的目的是确定TCDD的靶点，可能与介导暴露相关的头面部缺陷有关。

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. Project #1: The ABC superfamily is one of the largest known families of proteins. Members of the ABCB and ABCC subfamilies play significant roles in toxicology, pharmacology, and disease; however, mechanisms that regulate their expression are not well understood. The goal of this project is to identify functionally significant regulatory motifs in non-coding regions of ABCB and ABCC genes using comparative genomic and motif-finding strategies. This work is being done in collaboration with Drs. Tony Planchart (MDIBL, INBRE faculty) and Clare Congdon (USM; INBRE faculty). I further explored the following projects that stemmed from project #1, also in collaboration with Dr. Planchart. Project #2: Perturbation of defense pathways by low-dose arsenic exposure in zebrafish embryos Exposure to chemicals is a risk factor in the interplay between genetics, the environment and human disease. Adverse developmental consequences of exposure to arsenic in humans are largely unknown despite the potential for in utero exposure worldwide and results from studies suggesting that there is cause for concern (e.g., increased incidence of cancers, spontaneous abortions). This study aims to identify genes targeted by low levels of arsenic during vertebrate development to better understand mechanisms underlying arsenic toxicity. Project #3: Identification of a novel target of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) involved in craniofacial development The etiology of many birth defects involves interactions between environmental factors and genes that modulate important physiological processes. The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is found ubiquitously in the environment and is a known carcinogen and teratogen; however, the mechanisms underlying its toxicity are unclear. This study aimed to identify targets of TCDD potentially responsible for mediating exposure-related craniofacial defects.