Uncovering the mechanisms of action of an antiviral bacterium

Project Information

Mechano-Wolbachia

Grant agreement ID: 101040311

DOI

10.3030/101040311

EC signature date 15 September 2022

Start date 1 January 2023

End date 31 December 2027

Funded under

• European Research Council (ERC)

Total cost

€ 1 500 000,00

EU contribution

€ 1 500 000,00

Coordinated by

UNIWERSYTET JAGIELLONSKI
Poland

Periodic Reporting for period 1 - Mechano-Wolbachia (Uncovering the mechanisms of action of an antiviral bacterium)

Reporting period: 2023-01-01 to 2025-06-30

Summary of the context and overall objectives of the project

Wolbachia bacteria, a common endosymbiont of insects, offers a remarkable natural defense against pathogenic viruses. Wolbachia's protective ability is being harnessed in public health initiatives to safeguard human populations vulnerable to diseases like dengue and Zika. However, the precise mechanism by which Wolbachia confers this antiviral protection remains elusive. The Mechano-Wolbachia project seeks to unravel this mechanism, using the fruit fly, Drosophila melanogaster, as a model organism. The research is focusing on characterizing the intricate relationships between Wolbachia, viruses, and specific host tissues and cell types within Drosophila. A key aspect of this project involves refining and optimizing existing Drosophila cell line models to better study Wolbachia-mediated antiviral effects. At the same time, the project is developing innovative molecular tools tailored for this system, enabling precise and effective gene manipulations of partners.  

The significance of Mechano-Wolbachia lies in its potential to illuminate a completely new antiviral mechanism in insects. This can be applied to protect vulnerable insect groups, eg. pollinators, against viral infections and help us fight insect-borne pathogens. As many molecular pathways are conserved from insects to humans, uncovering the mechanism of antiviral protection can also pave the way toward new therapeutic strategies.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

A significant achievement of the Mechano-Wolbachia project has been the successful generation of single clones of Wolbachia-infected cell lines. Clonal cell lines constitute standardized and consistent experimental models, eliminating variability and enabling more reproducible research. These clonal cell lines provide a powerful tool for dissecting the molecular mechanisms underlying Wolbachia’s influence on host cells. Furthermore, we prepared samples for in-depth characterization of Wolbachia and associated virus infection in Drosophila tissues. These samples are earmarked for transcriptomics and imaging. These analyses will provide a detailed understanding of the molecular landscape of infected cells and tissues, revealing the specific host responses to Wolbachia and viral infection. Our approach will shed light on the complex interactions between the bacteria, the host, and the viral partner, providing a holistic view of the infections.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Cell lines are invaluable tools in biological research, especially for studying intracellular organisms like Wolbachia, which cannot be cultured outside their hosts. While Wolbachia-infected insect cell lines have been widely used to investigate the symbiont's diverse effects, including reproductive manipulations and antiviral protection, these lines often comprise mixed cell populations. This heterogeneity can lead to variability in Wolbachia infection, cell growth rates, and responses to experimental treatments across cell passages, hindering the reproducibility and interpretability of results. Our analysis revealed that monoclonal cultures derived from mixed cell populations exhibit distinct proliferation rates and Wolbachia infection statuses, demonstrating the inherent variability within the parental population. This observation highlights the risk of inadvertently selecting for specific subpopulations during experimental treatments, rather than observing a uniform effect on the entire culture. Our results will be crucial for the scientific community applying Wolbachia-infected cell lines in research and will be presented at the upcoming Wolbachia Conference 2025 in Japan.

At the same time, we are promoting our research and running an active outreach program. So far, our Laboratory has organized Małopolska Researcher’s Night and Biologist’s Night activities at the Jagiellonian University. We also engage in ERC grants-related education in Poland, and Polish science promotion internationally.