Descripción del proyecto
Perfil de las interacciones ARN-proteína en la infección por el virus sincitial respiratorio
Se calcula que el virus sincitial respiratorio (VSR) afecta a sesenta y cuatro millones de personas al año y provoca más de ciento cincuenta mil muertes. Los niños menores de cinco años y los ancianos corren mayor riesgo de contraer esta enfermedad grave. A pesar del impacto importante en la salud pública, el desarrollo de vacunas y antivirales ha sido un reto debido a los complicados mecanismos de multiplicación del virus, las interacciones virus-huésped y su patogenicidad. Con el apoyo de las Acciones Marie Skłodowska-Curie, el equipo del proyecto PARIS pretende cartografiar exhaustivamente las interacciones VSR-huésped, en particular las interacciones ARN-proteína, y caracterizar la respuesta celular a la infección. Para ello, el equipo utilizará un método integrado de proteómica y transcriptómica en paradigmas experimentales similares a la infección natural.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régimen de financiación
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinador
80333 Muenchen
Alemania