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High-throughput characterization of host promiscuity for precisely designed synthetic viral capsid

Objective

Traditional geographic ranges of insect pests are altered by globalization and climate change, resulting in emerging threats for natural ecosystems, agriculture and human health. It is urgent to improve our ability to swiftly develop targeted solutions to contain such threats, while minimizing unintended side effects on the environment.
Densovirinae are very small, single-stranded DNA viruses pathogenic to a variety of arthropods, including pythophagous caterpillars and grasshoppers, as well as disease vectors such as aphids and mosquitoes. Host ranges appear to vary considerably amongst even closely related densoviruses. A better understanding of the molecular mechanisms underlying virulence and specificity is necessary to evaluate the risk and opportunities associated with potential use in controlling natural insect populations.

We propose to discover these molecular determinants through the use of precisely designed libraries of viral genomes. We will leverage cost-effective and scalable DNA synthesis and sequencing technologies to generate high-throughput implementation and testing of precise molecular hypotheses. These will be informed by currently available knowledge and further deepened by bioinformatic analysis of natural sequences. We will produce ~106 controlled variants of the viral capsid as well as select viral regulatory sequence elements (enhancers, splicing and translation start sites). Resulting libraries will be subjected to multiplexed, deep-sequencing-based functional assays.

The scale of this approach will permit to reconstitute the sequence-structure-activity relationships required to relate viral genomes to host specificity and propagation efficiency. These data will support the development of models to predict the behavior of a viral genome in a new ecology, assess its potential for future evolution and inform the safe use of viral vectors for the targeted biocontrol of insect populations.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2014

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Coordinator

INSTITUT NATIONAL DE RECHERCHE POUR L'AGRICULTURE, L'ALIMENTATION ET L'ENVIRONNEMENT
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.

€ 185 076,00
Address
147 RUE DE L'UNIVERSITE
75007 PARIS CEDEX 07
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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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.

€ 185 076,00
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