n this project (extension of FFC#1/2018), the application of –omics methodologies, such as proteomics and lipidomics, allowed the researchers the identification of new proteins and lipids involved in the recovery of CFTR functionality. Molecules capable of interacting with the proteins identified by the experiments were tested to evaluate their ability to recover CFTR functionality. One of these molecules showed good results in the cell model (CFBE41o-cell line) but not in bronchial epithelial cells from a CF subject (primary cells).
By analyzing the protein localization in cells, the researchers also obtained a protein “map” that can help understand the cellular mechanisms underlying the recovery of CFTR. Since recent studies have shown the importance of the lipid composition of the cell membrane on the CFTR functionality, the researchers studied the lipidome (the set of lipids in cells) in the cellular model, treated and untreated with modulators (including Kaftrio). The experiments provided interesting information about specific lipids potentially involved in the functionality of CFTR. Further studies will be needed to verify the results in cells from CF subjects.

Pubblication

• Liessi N, Pedemonte N, Armirotti A et al. Proteomics and Metabolomics for Cystic Fibrosis Research, International Journal of Molecular Sciences, 2020 Aug; 21(15):5439.
• Liessi N, Pesce E, Braccia C et al. Distinctive lipid signatures of bronchial epithelial cells associated with cystic fibrosis drugs, including Trikafta, Journal of Clinical Investigation, 2020 Aug 20; 5(16): e138722.