All organisms, from bacteria to mammals, contain small RNAs (sRNAs) that participate in diverse cellular activities including RNA processing, mRNA stability, translation, etc. In the past few years, sRNAs have become one of the hottest topics with the discovery of novel classes of sRNAs and their involvement in regulatory processes (miRNAs/development, sRNA/bacterial stress responses, virulence, etc). In the enterobacterium E. coli, 50-250 sRNAs have been identified and/or predicted.
Of the few characterized so far, most acts as key post-transcriptional regulators by anti-sense mechanisms (base-pairing to target mRNA). These sRNAs regulate a variety of functions (e.g. from plasmid replication to bacterial virulence traits). Strikingly, most of them require the abundant Sm-like Hfq protein for activity, though its exact molecular mode of action is yet elusive.
The proposed project has two distinct, yet connected, goals:
1) Identification of new sRNA/target mRNA pairs in E. coli, and elucidation of the underlying regulatory processes.
2) Elucidation of the mechanism of action of the Hfq protein in sRNA-mediated regulation.
This project is multidisciplinary and involves experimental strategies from bioinformatics, molecular genetics and biology as well as advanced biochemistry. An elucidation of cellular functions of sRNAs in E. coli will aid our global understanding of their roles in gene regulation in all organisms and, in particular, in pathogenic bacteria. Furthermore, characterization of the role of H fq may provide functional clues relevant for similar proteins elsewhere (i.e. eukaryotic Sm-like proteins). Testifying to its importance, the field of sRNAs has received dramatically increased funding in the USA. Europe needs to take a lead in this area of high impact. The FP6 has recently recognized the general area of this project as being of high priority.
Fields of science
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