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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.

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

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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