The interplay of sRNAs Hfq and RNase E in the control of gene expression; a novel mechanism linked to pathogenic bacterial virulence

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With antibiotic resistance on the rise, research into understanding the workings of bacterial organisms is crucially important, as are new approaches to combating the infections they cause. When bacterial cells bring about infection, one of the first steps is that they must gain entry to the host cell. Recently scientists have found that an interlinked sequence of events occurs at the molecular level which aids the process of bacterial invasion into a host cell. They found that within the bacteria, messenger molecules (mRNA) played an important role in the invasion, but that these molecules were either degraded or stabilized by destruction (RNase E) or protection (Hfq) molecules respectively. It is also known that bacteria use signal molecules (sRNAs) to trigger either the destruction or the protection of the messenger molecules (mRNA). During the life of a bacterial cell, it is now understood that a complex sequence of interactions continually occurs between these molecules. Recent advances have taken the first steps to understanding this complex sequence of interactions, but quite how the events are communicated and regulated within the bacterial cell is still unknown. How does the destruction pathway work and how does the protector molecule prevent it? Are different signal molecules (sRNAs) treated differently? Can the protection pathway be interrupted in order to prevent the bacteria invading the host cell, and thereby preventing infection? Current data are lacking to answer these most fundamental questions. The aim of this research proposal is therefore to understand the interactions between the signal, messenger, protector and destructor molecules (sRNA, mRNA, Hfq and RNase E) found within a model bacterial cell. Only with this knowledge will it be possible to accurately inhibit the appropriate interactions to develop novel antibacterial approaches.