The term quorum sensing (QS) describes the ability of a population of unicellular bacteria to act as a single multicellular organism in a cell-density-dependent manner. Bacteria achieve this feat by the use of small diffusible molecules to exchange information among themselves. Examples of QS-controlled behaviors are bioluminescence, virulence factor expression and biofilm formation. These processes are advantageous to a bacterial population only when they are carried out simultaneously by its members. In recent years, a surprising new role has been found for several QS molecules diverse eukaryotes have been found to react strongly to the presence of these compounds. My aim is to examine the hypothesis that diverse eukaryotic species have developed mechanisms to react to the presence of specific bacterial QS molecules in a receptor-mediated fashion. Specifically, we aim to identify receptors that are highly specific for the Pseudomonas aeruginosa QSM 3-oxo-C12-AHL, as no receptor has been identified yet. This is a significant challenge, that we will address developing an innovative platform of chemical, biochemical and microbiological investigations. Identification of specific QSM receptors in eukaryotes will allow us to further understand the complex mechanisms of coexistence and evolution of coexistence between prokaryotes and eukaryotes. The insight obtained from these experiments could lead to: a) an increased understanding of important principles that guide the evolution of symbiotic relationships between competing species; b) new approaches in the treatment of P. aeruginosa infections, as well as to potential new drugs for the treatment of autoimmune diseases; c) the development of an integrated platform that will enable the discovery of unknown receptors for small hydrophobic bioactive compounds.