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RNAVirFitness SIGNED

The dark side of evolution: the deleterious mutational landscape of RNA viruses

Total Cost €

0

EC-Contrib. €

0

Partnership

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 RNAVirFitness project word cloud

Explore the words cloud of the RNAVirFitness project. It provides you a very rough idea of what is the project "RNAVirFitness" about.

antiviral    contribution    critical    epidemics    dfe    rates    pathogens    sex    tissue    ideal    unfeasible    host    culture    genetics    vivo    sequence    spectrum    overcome    multitude    notorious    rapid    accumulation    contexts    generation    safe    tackle    rare    characterizing    mainly    population    human    evolution    ngs    validation    therapeutic    anticipate    diseases    diverse    drivers    diversity    patients    cell    fundamental    gap    understudied    signatures    strategies    techniques    explore    consequence    beneficial    anti    context    deleterious    suggest    mutations    metabolic    perturbation    dependent    environmental    technically    linkage    represented    genetic    physical    strains    appreciable    vaccine    broad    proportion    date    spanning    class    single    harnessed    viruses    attenuated    times    extinction    fitness    perturbations    rna    evolutionary    models    vitro    shown    postulate    sequencing    biology    viral    array    integrate    mutation    reverse    pathogen    strategy   

Project "RNAVirFitness" data sheet

The following table provides information about the project.

Coordinator
TEL AVIV UNIVERSITY 

Organization address
address: RAMAT AVIV
city: TEL AVIV
postcode: 69978
website: http://www.tau.ac.il/

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Israel [IL]
 Total cost 1˙495˙625 €
 EC max contribution 1˙495˙625 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-06-01   to  2025-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    TEL AVIV UNIVERSITY IL (TEL AVIV) coordinator 1˙495˙625.00

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 Project objective

Mutations are fundamental drivers of evolution. Characterizing how mutations affect fitness is critical across diverse fields: from pathogen biology, to human genetic diseases, and models of population extinction. RNA viruses, notorious for their high mutation rates and rapid generation times, are ideal models for studying the effects of mutations. To date, deleterious mutations (i.e., mutations with a fitness cost) have been understudied as compared to beneficial mutations, mainly since it has been technically unfeasible to sequence each single rare deleterious mutation. Using novel next generation sequencing (NGS) techniques, we and others have recently overcome this gap, and shown that an appreciable proportion of viral genetic diversity is a consequence of a multitude of rare deleterious mutations. Here, we suggest investigating the distribution of fitness effects (DFE) across a diverse array of RNA viruses, spanning representatives of each class of major human pathogens, both in vivo (in patients) and in vitro (in cell culture). Next, we will focus on genetic linkage and context-dependent fitness effects of mutations. We postulate that over- and under-represented sequence contexts may represent signatures of host anti-viral activity. Finally, we will investigate how the DFE changes following an environmental perturbation (physical and metabolic changes, tissue type, and sex of the host). We will explore how the accumulation of deleterious mutations following rapid perturbations may lead to the extinction of the viral population, and how this can be used as a novel strategy to tackle viral epidemics. To this end we will integrate state-of-the-art NGS, population genetics modelling, and reverse genetics validation. Beyond their contribution to evolutionary biology, we anticipate that our results may be harnessed for the design of safe and effective attenuated vaccine strains, and the development of broad-spectrum antiviral therapeutic strategies.

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The information about "RNAVIRFITNESS" are provided by the European Opendata Portal: CORDIS opendata.

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