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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.

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

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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