Descripción del proyecto
La asociación de la infección por virus sincitial respiratorio y el asma
El virus sincitial respiratorio (VSR) es un microorganismo patógeno respiratorio frecuente y una de las principales causas de bronquiolitis y neumonía, sobre todo en niños pequeños y adultos mayores. El VSR está relacionado con el desarrollo de asma y otras afecciones respiratorias crónicas. El proyecto CLARITY, financiado con fondos europeos, tiene por objeto identificar los factores de riesgo genéticos y los mecanismos relacionados con la bronquiolitis grave inducida por el VSR en lactantes. Los investigadores utilizarán cohortes de España y Estonia y la inteligencia artificial para analizar los datos y determinar alteraciones y trastornos en los procesos celulares, moleculares y fisiológicos causados por el VSR. Los resultados del proyecto ayudarán a identificar posibles compuestos farmacológicos contra el asma provocada por el VSR.
Objetivo
Chronic respiratory diseases are non-communicable diseases for which infections by several respiratory viruses and human genetics constitute major risk factors. The molecular and physiological mechanisms of how these viral infections cause and contribute to non-communicable disease development are unknown.
Respiratory syncytial virus (RSV) is a virus that infects nearly all infants before the age of 2 years and that is linked to asthma development. We propose an integrative approach to identify genetic risk factors and mechanisms underlying virus-induced asthma. Specifically, using two national cohorts (Estonian and Spanish), we will identify human genetic risk factors and RSV strains that contribute to severe bronchiolitis. We analyse how RSV perturbs intracellular networks to change cellular properties that trigger asthma development. We will use Artificial Intelligence (AI)-based techniques to integrate generated data with the current biological knowledge, to generate RSV-induced perturbation signatures and to identify drug-like compounds able to revert the effects of the RSV-induced perturbations. We will validate both mechanisms and candidate compounds in patient derived airway organoid models and, when promising, in a controlled human infection model trial.
CLARITY will impact the understanding, prevention and possibly treatment of virus-triggered asthma. The results will enable development of a genetic risk score for long-term asthma development that enables personalised prevention campaigns, which will be developed jointly with patient groups. The molecular mechanisms discovered, and the drug-like compounds that revert the perturbation signatures, will enable development of mechanism-targeted drugs. Fundamentally, the mechanisms identified in this specific model for a strong viral contribution to non-communicable disease will likely represent general mechanisms of how viral infections cause onset and development of other non-communicable diseases.
Ámbito científico
- natural sciencescomputer and information sciencesartificial intelligence
- medical and health sciencesclinical medicinepneumologyasthma
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health scienceshealth sciencesinfectious diseasesRNA virusescoronaviruses
- medical and health sciencesbasic medicinemedical genetics
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HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinador
3584 CX Utrecht
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