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RecPAIR SIGNED

Genetic landscape of the homology search

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 RecPAIR project word cloud

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

lies    conclude    limit    linked    broken    chromosome    faithful    coupled    single    strains    dna    throughput    genome    breaks    characterised    dcas9    characterise    homologous    external    crispri    quality    phenotyping    screen    search    recombination    phenotype    microfluidic    elusive    movements    map    genes    library    pooled    first    situ    genetic    strand    combination    pairs    dynamics    directed    strands    sources    repair    mutagenesis    vulnerable    cell    damage    phenotypic    dsb    coli    dsbs    uses    microscopy    center    template    vivo    drives    internal    functional    sequencing    screening    defects    perhaps    hr    incorrect    genotyping    dumpling    create    characterisation    crispr    double    ageing    integrity    tested    replicated    life    homology    interrupted    threatening    recover    duplex    fluorescent    model    induction    probability    molecular    localises    refined    cancer    position    monitored    gene    central    lesions    landscape   

Project "RecPAIR" data sheet

The following table provides information about the project.

Coordinator
UPPSALA UNIVERSITET 

Organization address
address: VON KRAEMERS ALLE 4
city: UPPSALA
postcode: 751 05
website: www.uu.se

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 Sweden [SE]
 Total cost 191˙852 €
 EC max contribution 191˙852 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-06-08   to  2021-06-07

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UPPSALA UNIVERSITET SE (UPPSALA) coordinator 191˙852.00

Map

 Project objective

The integrity of genetic information is central to life, yet the DNA is vulnerable to damage from internal and external sources. Incorrect repair of DNA damage drives mutagenesis, loss of genetic information, ageing, and cancer. Double strand DNA breaks (DSBs) are perhaps the most threatening DNA lesions, where the integrity of both strands of the DNA duplex is interrupted at the same position. In E. coli, faithful repair of DSBs is possible only through the homologous recombination (HR) pathway which uses replicated chromosome as a template to recover the information. At the center of HR lies an elusive search process, during which broken strand localises and pairs with the repair template.

I will use a combination of CRISPR/dCas9 screening and in-situ genotyping of pooled library of strains to characterise the genetic landscape controlling the homology search. First, I will develop a low probability DSB induction method, to limit the DSB-formation to only a single chromosome per cell. Next, I will design and implement a whole-genome CRISPRi screen coupled to high-throughput sequencing and map the genes involved specifically in the homology directed repair of DSBs. The knowledge of the recombination-specific genes will allow to create a refined, high-quality phenotypic screen. In this screen the whole chromosome dynamics will be monitored and defects in the DNA movements will be characterised for each tested target with a microfluidic-based fluorescent microscopy. Each phenotype will be linked to a specific gene using the state-of-the-art in-situ phenotyping approach called DuMPLING. The functional characterisation of recombination genes will allow to conclude a molecular model of the search process in vivo.

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

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