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Uncovering the mechanisms of action of an antiviral bacterium

Project description

Bacteria with anti-viral properties: new treatment for insect-borne diseases?

Wolbachia are bacteria that occur naturally in various insect species, including mosquitoes as well as in nematodes. As such they have been proposed as a means of controlling insect-borne viral diseases. However, the mechanisms underlying the antiviral properties of Wolbachia remain poorly understood to date. Funded by the European Research Council, the Mechano-Wolbachia project aims to identify the genes responsible for this antiviral protection and the host cell types where the protection is conferred. The project will provide unprecedented evidence on an innovative way to protect insects against viruses with biomedical and veterinary relevance.

Objective

Animals and microbes interact in intricate ways. Wolbachia, a common intracellular insect symbiont, can manipulate reproduction and protect hosts from viruses. Thus, Wolbachia is an asset in the control of insect-borne diseases. However, as Wolbachia cannot be cultured outside of host cells or genetically manipulated, the mechanisms of its antiviral phenotype remain poorly understood, and this inhibits wider exploitation.
I have been working to remedy these deficiencies, and now stand poised to discover the mechanisms of Wolbachia-conferred antiviral protection by answering the following questions:
1) Where does the protection originate? Up to now, mechanisms of protection have been studied in whole organisms, often lacking resolution, or in cultured cells, which lack emergent properties. I will identify tissues and cell types of the host where protection starts. To do this, I will: a) quantify titers of Wolbachia and virus at early time points post-viral infection in insect tissues, b) measure gene expression of host and microbes to identify candidates for further molecular characterisation, and c) test the extent of the utility of widely adopted, yet unvalidated, cell-culture models of antiviral protection.
2) Which Wolbachia genes effect protection? Wolbachia research has historically been impeded by a lack of tools to study gene function. Here, I will deploy antisense technology, which I have recently developed, to interrogate function of candidate Wolbachia genes in the native system. I will also engineer new methods to target Wolbachia genes and proteins, based on my data on cell-penetrating peptide-mediated delivery of bioactive cargo to Wolbachia.
This project has two major outcomes: it will uncover Wolbachia factors responsible for Wolbachia-conferred antiviral protection, and it will transform Wolbachia and symbiosis research by creating tools to study symbiont gene function.

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(opens in new window) ERC-2021-STG

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Host institution

UNIWERSYTET JAGIELLONSKI
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.

€ 1 500 000,00
Address
UL GOLEBIA 24
31-007 KRAKOW
Poland

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Region
Makroregion południowy Małopolskie Miasto Kraków
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.

€ 1 500 000,00

Beneficiaries (1)

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