Functional genetics of Wolbachia proliferation and protection to viruses

Informations projet

WOLBAKIAN

N° de convention de subvention: 773260

DOI

10.3030/773260

Projet clôturé

Date de signature de la CE 3 Mai 2018

Date de début 1 Juillet 2018

Date de fin 30 Juin 2024

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 999 500,00

Contribution de l’UE

€ 1 999 500,00

Coordonné par

FUNDACAO CALOUSTE GULBENKIAN
Portugal

Periodic Reporting for period 4 - WOLBAKIAN (Functional genetics of Wolbachia proliferation and protection to viruses)

Période du rapport: 2023-01-01 au 2024-06-30

Résumé du contexte et des objectifs généraux du projet

Wolbachia is arguably the most prevalent intracellular bacterium in animals, infecting filarial nematodes and up to 66% of arthropod species. Wolbachia is maternally transmitted and can induce a large range of strong phenotypes in its hosts, from reproductive manipulation to antiviral protection, and act as a parasite or mutualist. However, very little is known about how it induces these phenotypes and how it interacts with the host at the molecular level. One main difficulty with this system is that Wolbachia has been genetically intractable. In this project we studied how Wolbachia confers protection to viruses, a phenomenon that is currently being applied to fight transmission of dengue and Zika viruses by mosquitoes. We also aimed at understanding how these endosymbiont titers are regulated, a crucial aspect of their biology.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Through an original forward genetic screen with identified and characterized new mutants of Wolbachia that overproliferate. We showed that the amplification or loss of a genomic region lead to over-proliferation and to abtter understanding of the role of this region in regulating growth. Moreover, we showed that Wolbachia proliferation rate in Drosophila melanogaster depends on the interaction between Octomom copy number, the host developmental stage, and temperature. Our analysis also suggests that the life shortening and antiviral protection phenotypes of Wolbachia are dependent on different, but related, properties of the endosymbiont.
Through the characterization on how environment modulates antiviral protection we found that in flies raised at low temperature Wolbachia does not confer protection against viruses. Through the further analysis of these conditions, including dual transcriptomics, we identified factor that may modulate Wolbachia presence in the fly and antiviral protection.
We also analysed how genetic variation in the host and in Wolbachia modulate Wolbachia growth. Through this we reached a better understanding of how evolution might act on this interaction and identified genes regulating this trait.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

We performed the first forward genetic screen in the genetically intractable Wolbachia. This and the analysis of genetic variation of Wolbachia impact on its growth provide a clear advance in the functional genetics of Wolbachia and how its growth is regulated. The analysis of the impact of temperature of development on Wolbachia antiviral protection helps to understand how the environment modulates host-endosymbiont interactions. It also will allow to identify the mechanisms of Wolabchia antiviral protection.