IDENTIFICATION OF REGULATORY MOTIFS IN ABC GENES BY COMPARATIVE GENOMIC ANALYSIS

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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.