The aim of our research is to understand biological functions and regulatory mechanisms of RNA-binding proteins (RBPs) and regulatory RNAs in pathogenic bacteria. This will lead to a better understanding of the regulatory decisions made by bacteria in adverse environments, such as inside the infected host.
RBPs are built of RNA-binding domains that recognize distinct motifs buried in RNA transcripts. The specific interactions between RBPs and their RNA ligands often result in regulation of gene expression, e.g. by activating or inhibiting mRNA translation, or by altering RNA stability. To understand the function of any given RBP, it is key to identify both its RNA ligands and the specific binding motifs. To do this in a comprehensive manner, we use CLIP-seq (crosslinking and immunoprecipitation sequencing) that allows for simultaneous identification of all RNA sequences bound by an RBP at any given moment. This approach can faithfully inform on cellular recognition motifs and RBP specificities, and reveal regulated cellular processes and regulatory mechanisms. We study Salmonella as a model system for bacterial pathogenesis. Salmonella causes typhoid fever and gastroenteritis leading annually to hundreds of thousands of deaths. Within the human host, a number of harsh environments force bacterial pathogens to rapidly change their physiological state by re-wiring gene expression and activate virulence gene expression programs. To fully understand the infection process, it is therefore critical to understand how gene expression is controlled within the pathogen.