PROGETTO DELIVER

Progetto FRRB 3269225 - Towards systematic characterisation of gene functions in adult organs: development of a liver-based in vivo essentiality screen

Dati del progetto

 
PROJECT SUMMARY

The incidence of chronic liver diseases rapidly increases in Europe, currently causing more than 200,000 deaths per year.  Combating this urgent health problem requires deeper understanding not only of molecular processes that drive disease development but also those that maintain hepatocyte viability under physiological conditions. However, progress in this field is limited by the lack of effective methods to systematically characterise gene functions in the complex environment of adult organs.

The researcher will address this challenge by developing the first in vivo loss-of-function genetic screen, which will be used to profile genes essential for hepatocyte viability in the adult mouse liver. This objective will be achieved through increasing the efficiency of parallel mutagenesis by CRISPR/Cas9 and deploying cutting-edge methods of gene delivery in vivo. An equivalent screen performed in the hepatocyte cell line will offer unprecedented insights into the differences between the in vivo and in vitro paradigms. DELIVER will build on the world-class expertise of the host institution in efficient and safe gene editing in mammalian models, while the researcher’s quantitative and analytical skills will be crucial for the downstream data analysis and integration. Unique environment of the research hospital will aid dissemination and communication of the project results to diverse audiences, including researchers, clinicians, patients and general public.

Overall, the MSCA fellowship will facilitate the researcher’s transfer from the field of epigenetics to high-throughput functional assays in clinically relevant paradigms. Tailor-made training in research competences and transferable skills as well as the expanded international network of contacts will provide a strong foundation for the future career transition to applied research in biomedical industry.