This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The ABC superfamily is one of the largest known families of proteins. Members of the ABCB and ABCC subfamilies play significant roles in physiology, toxicology, pharmacology, and disease; however, the mechanisms that regulate their expression are not well understood. The goal of this project is to identify functionally significant regulatory motifs in non-coding (5 -upstream, 3 -downstream and introns) regions of ABCB and ABCC genes.
Specific aims of this project are: 1) identify and fully annotate genomic regions for targeted ABCB and ABCC genes from evolutionarily divergent organisms; 2) clone and annotate targeted ABCB and ABCC genomic regions from the dogfish shark (Squalus acanthias) and the little skate (Raja erinacea) bacterial artificial chromosome (BAC) genomic libraries; and 3) conduct comparative analyses of ABCB and ABCC genomic sequences from these organisms to identify regulatory motifs in non-coding regions and validate functionality of these motifs experimentally. Three motif-finding algorithms (MEME, Gibbs motif sampler, GAMI) are being used in parallel, including a novel genetic algorithm approach (GAMI), being developed in collaboration with Dr. Clare Congdon (U. of Southern Maine), an INBRE project leader. Control studies were performed to assess the ability of these programs to identify motifs. GAMI continues to be modified to expand its capabilities. Probing of BAC libraries is underway in collaboration with Dr. Antonio Planchart (MIDBL) an INBRE project leader, and has identified several clones from the dogfish shark that contain at least one ABCB gene. Subsequent computational studies on ABCB genes will include these sequences as appropriate.
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