The "CORRADO E BRUNO MARIA ZAINI" FOUNDATION supports 2 projects for research into cystic fibrosis:
- CFTR MRNA ANALYSIS AS A KEY STEP TO UNDERSTAND THE ROLE OF CFTR GENE MUTATIONS IN CYSTIC FIBROSIS DISEASE EXPRESSION
Responsible person: Stefano Duga
(Dept. of Biology and Genetics for Medical Science, University of Milan)
Duration: 2 years .
Objectives:
In spite of the fact that sophisticated tests, through DNA analysis, are available to identify the mutations responsible for cystic fibrosis, in approximately 5% of patients with cystic fibrosis a complete molecular diagnosis cannot be obtained. Certain of the mutations that cause cystic fibrosis are located in regions of the gene that are not normally analysed, as this analysis would be too long and expensive with the technologies currently used. To discover these hitherto unidentified mutations (more specifically the "splicing" mutations) and to highlight changes to gene function, it is important to analyze the messenger RNA (mRNA), which is the molecule through which the gene DNA transfers the information needed for protein synthesis. The mRNA of the CFTR gene may be analyzed on nasal epithelium cells (collected through "brushing"). This project is intended to analyze the mRNA of the CFTR gene in a select group of patients in whom it has not been possible to identify the mutations responsible for the disease. In cases in which this analysis should not be decisive, ultra-massive sequencing (using the NGS or Next Generation Sequencing technique) of the entire gene will be performed. In addition to cystic fibrosis patients, subjects showing a disease that is totally similar to cystic fibrosis but without the fundamental diagnostic aspect (positivity to the sweat test) will also be studied.
In spite of the fact that sophisticated tests, through DNA analysis, are available to identify the mutations responsible for cystic fibrosis, in approximately 5% of patients with cystic fibrosis a complete molecular diagnosis cannot be obtained. Certain of the mutations that cause cystic fibrosis are located in regions of the gene that are not normally analysed, as this analysis would be too long and expensive with the technologies currently used. To discover these hitherto unidentified mutations (more specifically the "splicing" mutations) and to highlight changes to gene function, it is important to analyze the messenger RNA (mRNA), which is the molecule through which the gene DNA transfers the information needed for protein synthesis. The mRNA of the CFTR gene may be analyzed on nasal epithelium cells (collected through "brushing"). This project is intended to analyze the mRNA of the CFTR gene in a select group of patients in whom it has not been possible to identify the mutations responsible for the disease. In cases in which this analysis should not be decisive, ultra-massive sequencing (using the NGS or Next Generation Sequencing technique) of the entire gene will be performed. In addition to cystic fibrosis patients, subjects showing a disease that is totally similar to cystic fibrosis but without the fundamental diagnostic aspect (positivity to the sweat test) will also be studied.
- TASK FORCE FOR CYSTIC FIBROSIS
Responsible person: Luis Galietta
(Molecular Genetics Lab., G. Gaslini Institute, Genova)
Duration: 3,5 anni.
Objective:
The development of the new FS08del correctors and potentiators and possibly other Cystic Fibrosis mutations.
The project, expected to last three and a half years, is subdivided into three phases:
1) Hit identification (identification of the active starting compounds);
2) Hit to lead (from the active starting compound to the leader compound);
3) Lead optimization (optimization of the leader compound).