A new paper, published in BMC Cell & Bioscience Journal, first-authored by Lúcia Santos, coordinated by Carlos M. Farinha – respectively, researcher and principal investigator at the Cystic Fibrosis Research group, included in the Functional Genomics and Proteostasis Group, and with the collaboration of Margarida Gama-Carvalho, PI from RNA Systems Biology Lab; both at Ciências ULisboa – analyzes five different mutations in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene and the associated mechanisms that causes disease, being one of them found in patients who are still in need of effective therapy. Know more below.
What was the starting point that led to the current research?
Cystic Fibrosis (CF) is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, but phenotypic heterogeneity observed in people with CF (PwCF), suggests the involvement of other genes. By combining omics analysis, we aimed to identify which genes and proteins would contribute to this phenotypic variability.
What is the main finding reported in this paper?
All five different CFTR mutations studied and reported in this paper had the same in common – causing the loss of CFTR protein function. However, what we found was that the differentially expressed genes and proteins identified, which were grouped in functional signatures, were much more associated with each specific mutation (or class of mutation) than with the CFTR loss-of-function phenotype.
If you had to explain the main finding to a 5-year-old child, how would you do it?
The five different CFTR mutations represent five different supervillains belonging to the CF squad, like in the Marvel comics. In our study, we did a detailed analysis of each one of these supervillains and found their specific weaknesses that can be targeted to fight the CF squad.
Why is it important for the scientific community and for society at large?
While four CFTR modulators are currently approved for 80-90% of PwCF, the remaining CF community is still in need of effective therapy. The identification of the mechanisms through which each mutation causes disease will likely contribute to the identification of new therapeutic targets and/or biomarkers for CF.
What are the next steps?
In this study, we identified a large number of genes and proteins associated with each one of the five CFTR mutations studied. The next steps would be to investigate in detail specific genes and proteins whose expression is altered and use them to find novel targets that can rescue CFTR protein function.
Know more about FunGP group here.
Read the full paper here.
[Some of the] Authors [from left to right]: Lúcia Santos, Violeta Railean, Margarida Amaral, Margarida Gama-Carvalho and Carlos Farinha [images provided by the researchers]