Descrizione del progetto
Profilazione delle interazioni RNA-proteine nell’infezione da virus respiratorio sinciziale
Si stima che il virus respiratorio sinciziale (VRS) colpisca ogni anno 64 milioni di persone, causando più di 150 000 decessi. I bambini sotto i cinque anni e gli anziani sono i soggetti più a rischio di questa grave malattia. Nonostante il significativo impatto sulla salute pubblica, lo sviluppo di vaccini e antivirali è stato difficile a causa dei complicati meccanismi di moltiplicazione del virus, delle interazioni virus-ospite e della patogenicità. Con il sostegno del programma di azioni Marie Skłodowska-Curie, il progetto PARIS intende mappare in modo completo le interazioni VRS-ospite, in particolare le interazioni RNA-proteina, e a caratterizzare la risposta cellulare all’infezione. A tal fine, il team si avvarrà di un approccio integrato di proteomica e trascrittomica in paradigmi sperimentali che assomigliano all’infezione naturale.
Obiettivo
Respiratory Syncytial Virus (RSV) is a major cause of severe lower respiratory tract infections and a major cause of mortality in children under 5 years old and the elderly worldwide. While RSV impose a huge disease burden on public healthcare system, the development of effective vaccines and specific antivirals is impeded by a lack of knowledge of virus multiplications mechanisms, virus-host interactions or pathogenicity. Here, we propose to comprehensively map RSV-host interactions and characterize the cellular response to infection through an integrated multi-omics approach and using experimental systems close to natural infection. This project will combine my expertise in RSV biology and the host laboratory’s profound experience in systems biology analysis. By using state-of-the-art-of proteomics and transcriptomics, we will characterize the RSV RNA-bound proteome as well as the protein-protein interactome, analyze the proteome of cells expressing the individual viral proteins (effectome), and assess the influence of RSV infection on cellular mRNA expression, protein abundance, and phosphorylation. We will systematically map the identified viral-induced perturbations onto a network of known cellular protein-protein interactions and signalling pathways. This comprehensive network will highlight RSV-induced perturbations and pinpoint RSV host dependency-factors, whose functional importance and therapeutic potential will be assessed by conducting genetic and drug-based loss and gain of function experiments. Biochemical and structural methods, and further analyses of the cellular response in genetically or drug-perturbed cells will yield insights into the molecular function of selected proteins. The proposed multilevel approach will thus reveal yet unstudied proteins and pathways determining RSV growth, pathology or viral host defense mechanisms, which will shed light on unresolved questions of RSV biology, and reveal hotspots amenable to therapeutic intervention.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinatore
80333 Muenchen
Germania