An integrated investigation of regulatory RNAs and their interacting proteins in bacteria models

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Recent genome-wide strategies and computational approaches enabled the discovery of an unexpectedly high number of small RNAs (sRNAs), their protein co-factors, and of short open reading frames (sORFs). Pioneering work, mainly in Gram-negative model bacteria, characterized many of these novel gene products as important regulatory factors and elucidated novel regulatory mechanisms and concepts. However, physiology, gene content and mechanisms to regulate gene expression are extremely diverse in other bacterial lineages. Therefore, the landscape of sRNA and sORF based mechanisms has to be studied in evolutionarily distant bacteria that possess different lifestyles and molecular machineries. IntRNAReg will use the pyogenic and toxigenic Gram-positive pathogen Staphylococcus aureus and the photosynthetic Synechocystis 6803. We will generate RNA interactome maps, and characterize the functions of newly identified sRNA-binding proteins and sORF encoded by sRNAs. Integrative statistical and computational analysis will generate information on the particular regulatory and physiological settings and will help to answer several questions: Which genes are regulated by multiple sRNAs and serve as regulatory hubs? What are pathways linking stress and environmental changes, metabolism adaptation and virulence expression integrated by sRNAs? What is the complexity of the regulatory events mediated by sRNAs and their interacting proteins? Do sRNAs including sRNAs carrying sORFs contribute to the population behavior and to host-pathogen interactions? The partners will combine their complementary expertise at the interface of computational and RNA biology, molecular microbiology, and microbial systems biology to delineate the functions of sRNAs and their protein partners associated with virulence and acclimation to environmental changes opening new avenues for therapy and biotechnology.