Recently a cluster of post-translational modifications (PTM) associated with functional recovery of F508del, named PTM code, has been identified. In this PTM code, the phosphorylation CK2 dependent of three sites and methylation/ubiquitylation of lysine has been suggested to have a pivotal role in F508del functional rescue. However, it is not still clear if these posttranslational modifications are a consequence or are required for the recovery. The aim of the project is to assess the real contribution of these modifications for functional F508del recovery. The goal is indeed to understand if it is possible to favour F508del correction controlling these post-translational modifications. Researchers will use F508del-CFTR CFBE expressing cells. All the modified sites identified in the PTM code will be mutated. Mutants will be transfected and the rescue efficiency will be assayed. The possibility to modulate these post-translational modifications to favour F508del recovery will be investigated.