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CLARITY

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Causative Link between respirAtory syncytial viRus and chronic lung diseases: Id...

Causative Link between respirAtory syncytial viRus and chronic lung diseases: Identifying Targets for therapY 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 infecti... ver más

31/12/2028

UMC UTRECHT

7M€

Presupuesto del proyecto: 7M€

Líder del proyecto

UNIVERSITAIR MEDISCH CENTRUM UTRECHT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-01-01

HORIZON-HLTH-2023-DISEASE-03-18: Contribution to the Coalition for E...

I+D

Cerrada hace 55 años

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UMC UTRECHT

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Duración del proyecto: 59 meses Fecha Inicio: 2024-01-01
Fecha Fin: 2028-12-31

Líder del proyecto

UNIVERSITAIR MEDISCH CENTRUM UTRECHT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 7M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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