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Small RNAs in immunity and regulation of giant endogenous viral elements in eukaryotes

Project description

Immunity against giant viruses

Giant viruses are unusually large DNA viruses that are often visible by light microscopy with genomes exceeding those of many bacteria. Evidence shows that giant viruses can integrate into the genome of many eukaryotic species, forming giant endogenous viral elements (GEVEs). A unicellular relative of animals was recently found to carry hundreds of these elements. Normally silent, GEVEs were reactivated when DNA methylation was removed, leading to the expression of both viral sequences and those involved in small RNA (sRNA) pathways. With the support of the Marie Skłodowska-Curie Actions programme, the SMALLGIANT project investigates if reactivated GEVEs produce sRNAs that contribute to antiviral defence and reflect co-evolution with giant viruses. Project findings will shed light on RNA-based immunity in unicellular eukaryotes.

Objective

In this project, we aim to investigate the role of small RNAs (sRNAs) in defending against giant virus infections. Giant viruses are eukaryotic viruses with exceptionally large genomes, some of which surpass the size of bacterial genomes. Remarkably, giant virus integrations have been found across various eukaryotes, leading to the formation of giant endogenous viral elements (GEVEs). Among the reported GEVEs, the host group (Dr. de Mendoza’s laboratory) has identified a unicellular relative of animals that harbours hundreds of GEVEs—more than any other known eukaryote. This observation suggests that these viral integrations may confer a beneficial role to the host. Although GEVEs are typically transcriptionally silent, the removal of DNA methylation triggers the reactivation of many viral genes, mimicking an infection. Notably, proteins related to sRNA biogenesis are upregulated during this reactivation, indicating that sRNAs may play a role in post-transcriptional silencing of the endogenized viruses, as no viral particles are formed. Based on these findings, we hypothesize that GEVE-derived transcripts generate sRNAs that help defend against future infections.To explore this hypothesis, I will bring my expertise in small RNAs to the host lab, aiming to deepen our understanding of how sRNAs co-evolved with GEVEs and how they may function in immunity against giant viruses. My focus will be on key unicellular eukaryotes that possess the genetic machinery necessary for sRNA processing and show evidence of containing GEVEs. The outcomes of this project have the potential to open a new field of research. If sRNAs are indeed involved in immunity, they could be leveraged to protect these species against new infections. Additionally, we propose various outreach activities to engage the public and highlight the importance of studying the evolution of unicellular eukaryotes and giant viruses.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European 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

QUEEN MARY UNIVERSITY OF LONDON
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.

€ 276 187,92
Address
327 MILE END ROAD
E1 4NS LONDON
United Kingdom

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Activity type
Higher or Secondary Education Establishments
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Total cost

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