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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.

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

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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