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The role of the antiviral RNA interference response in the C. elegans–Orsay virus pathosystem

Project description

The molecular mechanics of how RNA interference fights viral infections

RNA interference (RNAi) is a key antiviral defense mechanism used by cells to detect and silence viral genetic material. However, the detailed mechanism of this process remains unclear. With the support of the Marie Skłodowska-Curie Actions programme, the VirAgo project will investigate the RNAi process using the C. elegans and Orsay virus model. To understand the precise implication of RNAi in the antiviral immune response, the researchers will explore how RNAi proteins interact with the virus and if their absence boosts immune responses. The project will also identify the makeup of virus-specific RNAi complexes and uncover how RNAi prevents viruses from spreading.

Objective

Viruses infect all known living organisms, and the RNA interference (RNAi) response is one of the main defense mechanisms cells use against viruses. Even though we have a general understanding of the players involved in the antiviral RNAi response, with some systems more characterized than others, we still lack mechanistic details about the process. For example, in the C. elegans-Orsay virus pathosystem, loss of certain RNAi proteins can be advantageous for the virus, but it is still unclear whether this is because the virus highjacks the RNAi machinery for its own advantage or because the absence of certain RNAi proteins frees up resources which can then be used for antiviral defense. Moreover, preliminary results show that there are distinct viral RNAi silencing complexes, but the composition and function of these complexes is still unknown. Finally, the RNAi response seems to prevent multicellular viral colonization through yet unidentified mechanisms. In this proposal we aim to address these three open questions to improve our understanding of the role of RNAi in the defense response to a viral infection. We will perform a comprehensive analysis of the antiviral RNAi pathway and the Argonautes – the main effectors of the RNAi pathway –, their interactors and targets upon Orsay virus infection. We will use a multidisciplinary approach, combining in-depth analyses from virology, cell biology, genetics, genomics and developmental biology. This will be possible due to the collaboration between the researcher and the laboratories of Prof. Elena, the coordinator and virology expert, and Prof. Claycomb, the outgoing phase host and cell biology and small RNA regulation expert. The expertise the researcher will obtain goes beyond the research in either laboratory and will help her crystalize the unique research profile necessary to take her career to the next level of independence.

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HORIZON-TMA-MSCA-PF-GF - HORIZON TMA MSCA Postdoctoral Fellowships - Global Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Net EU contribution

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€ 223 428,00
Address
CALLE SERRANO 117
28006 MADRID
Spain

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Comunidad de Madrid Comunidad de Madrid Madrid
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Research Organisations
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