We wi11 continue the development of computer methods for analyzing gene regulation. We will further enhance methods to identify regulatory sites from the promoter regions of co-regulated genes. Included in the improvements will be better ways of identifying multiple transcription factors that act coordinately to regulate gene expression. We will also study the evolution of regulatory networks in bacteria. By comparing the homologous regulons in several bacterial species we can study the gain and loss of gene from common regulatory pa ways, the rates at which binding sites specificities change, and the duplication and divergence of regulatory proteins and the genes they regulate. We wil1 continue the development and enhancement of methods to predict RNA structures, especially comparative-based methods that attempt to find common structure, for collections of sequences These methods will be applied to several types of sequences including: { em in vitro} selection product; structural RNA families; mRNA motifs involved in post-transcriptional regulation of gene expression. Each of these projects will be enhanced through collaborations with other groups, primarily experimentalists, who are interested in the application of our methods to their biological problems.
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