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Post-transcriptional regulation of influenza A virus RNA

Project description

Insights into the role of post-transcriptional processes in the influenza A virus life cycle

Influenza A viruses (IAV) infect and spread among people every winter, and are also the primary agent of every flu pandemic over the last 100 years. The EU-funded PTFLU project will focus on an understudied aspect of the IAV life cycle, the post-transcriptional regulation of IAV RNA. Research over the years has provided significant knowledge about the post-transcriptional regulation of cellular mRNAs. PTFLU wishes to extend these findings in IAV by identifying the locations of various RNA modifications present in both human and avian IAVs and studying their impact on RNA characteristics. Combined with insights into the ribosomal machinery implicated in IAV mRNA translation, this information will unveil important aspects of IAV biology and life cycle.

Objective

This research proposal aims to significantly alter our understanding of the critical role post-transcriptional processes play in the influenza A virus (IAV) life cycle. Post-transcriptional regulation of cellular mRNAs has seen a lot of research interest in recent years, including projects looking at the effects of RNA modifications and ribosome specialisation. However, much less attention has been paid to the effects these processes have on the viral life cycle. This project focuses on the post-transcriptional regulation of both IAV mRNAs and negative strand vRNAs. However, outcomes of this work will have a profound effect on our perceptions of the regulatory processes affecting a wide range of viral RNAs. In fact, by better understanding the roles of these processes on viral RNAs, such as IAV, we can also uncover novel functions on cellular mRNAs.
This project comprises 5 work packages with 11 intermediate goals. We will first identify the locations of various modifications present on IAV RNAs across multiple strains in both human and avian infected cells, significantly expanding on our current understanding, while exploring the potential for species-specific adaptions. Through mutagenesis and RNA capture techniques, we will evaluate how these modifications affect RNA characteristics and what effector proteins are involved in these processes. We will also use this information to determine the composition of ribosomes actively translating IAV mRNAs and evaluate whether specialised ribosomes are involved in the normal IAV life cycle. Finally, we will focus on the roles of RNA modifications on vRNAs, which should be quite distinct from mRNAs, and the host proteins that specifically bind, or are blocked from binding, sites of modification. This is an ambitious, multifaceted project that will have a direct impact on our understanding of IAV biology, and also provide novel insights of value to multiple disciplines including virology, RNA biology and protein translation.

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Topic(s)

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ERC-STG - Starting Grant

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Call for proposal

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Host institution

THE QUEEN'S UNIVERSITY OF BELFAST
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.

€ 1 568 010,00
Address
UNIVERSITY ROAD LANYON BUILDING
BT7 1NN BELFAST
United Kingdom

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Region
Northern Ireland Northern Ireland Belfast
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 568 010,00

Beneficiaries (1)

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