Project description
A new host orchestrator of virus infection
Upon infection, viruses induce host mRNA degradation, a process known to be orchestrated by the exonuclease XRN1. Human cells lacking this protein are refractory to the mosquito-borne sindbis (SINV) virus, clearly underscoring the importance of XRN1 in the infection process. However, the precise mechanism of its action remains elusive. The aim of the EU-funded RNAdeg-Virus project is to investigate the targets of XRN1 using cutting-edge system-wide approaches and delineate the molecular events that trigger XRN1 activation. The project's results will lead to the identification of potential targets for antiviral drugs, with obvious medical and socio-economic consequences.
Objective
Commandeering the cellular gene expression machinery is essential for viruses in order to replicate their genome and ensure the production of their progeny. One of the major events occurring during viral infection is the virus-induced host mRNA degradation, process orchestrated by the exonuclease XRN1. However, the exact role of this enzyme remains controversial and largely elusive. An exciting stepping stone for studying XRN1 involvement in virus infection is the observation that human cells depleted of this protein are refractory to the infection of sindbis (SINV), a mosquito-borne virus. This suggests that this exonuclease is essential for SINV infection. It has been shown that the cellular RNA is massively degraded upon infection and that RNA degradation is the main force shaping the host transcriptome. Thus, I propose to identify the cellular and viral RNAs directly bound to and regulated by XRN1, using cutting-edge system-wide approaches, which will shed light on the targetome of this protein. Moreover, I plan to study how XRN1 is triggered, for instance by virus-induced posttranslational modifications or by differential protein complex assembly using mass-spectrometry analysis. Discovering the molecular events that activate XRN1 will be fundamental for determining its precise molecular mechanism of action and why it is important for viral infection. Additionally, the outcomes of this multidisciplinary approach will be beneficial for studying gene expression and RNA degradation-related processes, such as cancer. This innovative project will generate a vast amount of valuable data, which will allow to dissect the infection mechanisms of a mosquito-borne virus, leading to the identification of potential targets for antiviral drugs, with a consequent strong medical and socio-economic impact.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics RNA transcriptomes
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antivirals
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2019
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
OX1 2JD Oxford
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.