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Influenza RNP

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A structural and functional understanding Influenza virus mRNA production in the...

A structural and functional understanding Influenza virus mRNA production in the context of the transcriptionally functional ribonucleoprotein RNP particle. Influenza is a major public health burden, with seasonal outbreaks contributing significantly to mortality worldwide, and the emergence of pandemic strains remaining an ever-present threat. Influenza drug and vaccine conception ef... ver más

30/06/2023

EMBL

185K€

Presupuesto del proyecto: 185K€

Líder del proyecto

EUROPEAN MOLECULAR BIOLOGY LABORATORY No se ha especificado una descripción o un objeto social para esta compañía.

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2023-06-30

MSCA-IF-2020: Individual Fellowships

I+D

Cerrada hace 4 años

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1 Participantes

EMBL

184.71K€ | Lider

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Duración del proyecto: 26 meses Fecha Inicio: 2021-04-30
Fecha Fin: 2023-06-30

Líder del proyecto

EUROPEAN MOLECULAR BIOLOGY LABORATORY No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 185K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Influenza is a major public health burden, with seasonal outbreaks contributing significantly to mortality worldwide, and the emergence of pandemic strains remaining an ever-present threat. Influenza drug and vaccine conception efforts are aided by a thorough understanding of its molecular biology. A key aspect of the influenza lifecycle is the production of capped and poly-adenylated messenger RNA by the heterotrimeric influenza polymerase (FluPol). Ground-breaking work performed by the Cusack lab, has described with residue-resolution detail, the FluPol structures that form during transcription of short, non-nucleoprotein (NP) bound viral RNAs (vRNAs). However, influenza transcription in vivo occurs within the ribonucleoprotein (RNP) particle and does not utilise naked genome segments. The viral RNP (vRNP) is a super-helical complex composed FluPol bound at the conserved 3′ and 5′ ends of a vRNA, which is coated with NP. The current low-resolution structures provide little information about the molecular details of vRNP function, particularly, how NPs interact with FluPol and the vRNA template. Via an inter-disciplinary approach, I will utilise cryo-electron microscopy methods, transcription assays and single-molecule fluorescence, to obtain the first high resolution structure of a dynamic influenza vRNP, with a particular focus on the spatial organisation of NPs relative to FluPol. In addition to this work facilitating future influenza drug research, it will provide a basis to investigate the vRNP during other lifecycle stages and act as proof-of-principle for study of other viral protein-RNA complexes, such as those from corona-, arena- and bunyaviruses. Work will be performed in the groups of Stephen Cusack and Olivier Duss based at EMBL Grenoble and Heidelberg, respectively. Here, I will have access to world-leading facilities and training opportunities, supporting my growth as an independent researcher and an expert in RNA virus structural biology.

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