Rapid adaptation to changing conditions is one of the remarkable characteristics of bacterial life forms. Nowadays, de novo bacterial adaptation is mostly evident from acquired antibiotic resistance, new appearance of virulence traits, and spontaneous toxic compound removal. The past ten years have dramatically changed our view on the importance of horizontal gene transfer in adaptation through the availability of hundreds of bacterial genome sequences. In particular, it has become much more evident that adaptation is to a large extent determined by discrete regions of DNA that differ among closely related species. There has been a real revolution in our appreciation of the importance of transfer mechanisms resulting from chromosomally integrated mobile DNA elements, or 'genomic islands' (GEI), which frequently carry the functions for virulence factors, antibiotic resistances or toxic compound degradation. Despite their widespread occurrence in bacterial chromosomes, however, very little is known about the factors controlling GEI transfer, successful integration in the bacterial host and long-term evolutionary establishment. This project will focus on a model GEI, called ICEclc, which is representative for a large class of elements in primarily Gamma- and Betaproteobacteria. ICEclc is self-transferable to quite a few different recipient bacteria, and invokes a clear phenotype, and is thus is an excellent model for this research. ICEclc seems to establish itself without large fitness cost on the host, and hence, we are highly interested to know if and which specific molecular factors contribute to this success. Our working hypothesis is that ICEclc and other GEI have evolved specific mechanisms to ensure efficient transfer and subsequent establishment in the host, which contributes to their widespread distribution. The specific goals of the underlying proposal are, therefore, to discover, which factors encoded by ICEclc (as model for GEI more in general) give adaptive advantages to self-distribution and/or host establishment. In addition, we would like to study which host factors are important in this evolutionary adaptation. In particular we would like to follow host-ICEclc establishment after entry into the host and understand which changes are pivotal for successful host-GEI interaction.