Infections from Aspergillus fumigatus can turn out to be very serious for CF patients and the currently available antifungal drugs are known to have important side effects, hence the priority for the development of new therapeutic approaches. The project’s proposed strategy consists in identifying therapeutic targets that would favorably impact the host (i.e. the patient), and negatively affect the pathogen. Sphingosine 1-phosphate lyase (SPL) is well suited for this purpose, as it is an enzyme involved in the metabolism of sphingolipids, that can be found both in humans and in the fungus. In fact, CF patients show alterations in the sphingolipids’ metabolism, which favor inflammation and increase susceptibility to lung infections, therefore they would benefit from the inhibition of SPL. At the same time, if exercised on Aspergillus, this inhibition is toxic. Researchers will use already known inhibitors of SPL and will perform experimental tests in vitro, in vivo (animal models) and ex-vivo (primary CF bronchial cells). The most promising inhibitors will then be prepared to allow direct administration into the lungs. With just one drug we could improve the patient’s immune response and, at the same time, weaken the pathogen.