Every year in the European Union, an estimated 25000 patients die because of a serious resistant bacterial infection acquired in hospital. The bacterium Staphylococcus aureus is a main opportunistic pathogen responsible for food poisoning, skin infections and nosocomial infections. In the recent years, small ribonucleic acids (sRNAs) have attracted great interests as ubiquitous regulators. Some of them have been directly related to commitment of virulence of this species. However, a serious bottleneck in unraveling their biological roles is due to the difficulty in identifying targets of the RNome (any non-conventional RNA with regulatory functions). There is a strong and urgent need to propose and use novel technologies for target detections of the bacterial RNomes. SarHyb intends to identify the primary molecular targets of staphylococcal RNome with a multidisciplinary approach. Therefore, t will combine the use of novel bacterial genetic hybrid systems, molecular biology and biochemistry. The researcher has an in depth expertise in the use or large-scale studies and yeast as a surrogate system which he used during his postdoctoral training at Yale University (USA). The main objective of SarHyb is to provide a list of prioritized sRNA candidates to target for the development of novel drug therapy directed against this pathogen. The transfer of knowledge from the researcher will consolidate the position of the host institution as a leader in Europe and worldwide in the use of hybrid-systems.Major Scientific findings expected during the course of the project include the development of the first bacterial hybrid systems devoted to RNA-target identification, an exhaustive list of mRNA and proteins directly regulated by sRNAs, and an in-depth understanding of the molecular signals allowing S. aureus to adapt to its environment. If successful, this ambitious research project will impact both basic and translational research at the European Union level.