The major trust of this project is to define genetic factors that influence the severity of CF lung disease by using the high genetically diverse mouse resource population named the Collaborative Cross (CC) mice as novel tool. CC strains of mice will be evaluated for susceptibility to P. aeruginosa infection to identify mouse strains presenting deviant disease phenotypes amenable for genetic analyses. Strong candidate genes associated with P. aeruginosa susceptibility within the mapped genomic region/s will be identified and validated in CF mice. Finally, the results obtained from this project could be translated into human population in association study among CF patients with or without P. aeruginosa infection and evaluated on the basis of patient respiratory function. Overall, the project will provide powerful tools to address critical issues regarding the risk of P. aeruginosa lung colonization among CF patients.