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Interrogating RNA-protein interactions underlying SARS-CoV-2 infection and antiviral defense

Objective

The global COVID-19 pandemic underscores the need to better understand its causative agent, SARS-CoV-2, and the various other emerging viruses threatening human health. Like many human viruses, SARS-CoV-2 utilizes RNA as its replicated genetic material and its template for translating the virus's proteins. Ongoing research into SARS-CoV-2 and other RNA viruses has largely focused on understanding the function of their encoded proteins, revealing key roles in host cell entry, viral replication, and immune suppression. In contrast, little is known about the set of viral RNAs and how they interact with host machinery as part of a virus's replication cycle in infected cells. My group discovered a large collection of viral and host proteins that bind the genomic and subgenomic RNAs of SARS-CoV-2 during infection. This collection provides an excellent starting point to work toward the goal of my proposed ERC Starting Grant project: decoding how these interactions shape the viral RNA life cycle and contribute to antiviral defense mechanisms. My overarching hypothesis is that SARS-CoV-2 dynamically modulates RNA-protein interactions in the host to facilitate functions of genomic and subgenomic viral RNAs at different stages of the replication cycle. To test this hypothesis, I have devised three research objectives:

1) Decode mechanisms of host-mediated control over the life cycle of SARS-CoV-2 RNAs.
2) Map with temporal resolution which host cell proteins engage each SARS-CoV-2 RNA type.
3) Elucidate the role of host proteins that moonlight as RNA binders in SARS-CoV-2 infections.

If successful, this project will identify novel pro- and antiviral host factors in SARS-CoV-2 infections and reveal underlying RNA regulatory mechanisms. In turn, these insights will provide an RNA-centric view of viral infections and identify candidate factors and pathways as therapeutic targets to treat viral diseases.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

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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.

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.

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2021-STG

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Host institution

RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Net EU contribution

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.

€ 1 056 482,37
Address
SEMINARSTRASSE 2
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Higher or Secondary Education Establishments
Links
Total cost

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.

€ 1 056 482,39

Beneficiaries (3)

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