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DiVineGenoMe SIGNED

Decoding cell-to-cell variation in genome integrity maintenance

Total Cost €

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EC-Contrib. €

0

Partnership

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 DiVineGenoMe project word cloud

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

determinants    automated    impacts    exists    mechanism    significantly    content    single    last    dna    variability    trigger    unexplored    deal    transcription    instance    dissect    relapse    quantitative    senses    variation    genotoxic    cohorts    outcome    independently    genome    maintenance    became    reveal    faithful    replication    limelight    coordinates    heterogeneity    imaging    double    causes    damage    transactions    stability    therapeutic    intriguing    newly    clear    strand    disease    homogenize    bridge    insights    cancer    stress    tumor    cells    sites    hitherto    repair    capacity    breaks    mutations    genomic    survival    cellular    fate    cell    systematically    continues    integrity    transformation    sophisticated    background    network    ways    genetic    uncover    unknown    dynamic    malignant    phenomenon    lesions    context    chromatin    transitions    compartmentalization    individual    therapies    surprisingly    reached    molecular   

Project "DiVineGenoMe" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAT ZURICH 

Organization address
address: RAMISTRASSE 71
city: Zürich
postcode: 8006
website: http://www.unizh.ch

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 Switzerland [CH]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-STG
 Funding Scheme ERC-STG
 Starting year 2017
 Duration (year-month-day) from 2017-04-01   to  2022-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAT ZURICH CH (Zürich) coordinator 1˙500˙000.00

Map

 Project objective

Cells must ensure the integrity of their genome, and failure to do so can lead to mutations and cause disease. A sophisticated molecular network senses genomic lesions and coordinates their faithful repair with other DNA transactions, including transcription and DNA replication. Research over the last years has significantly advanced our understanding of the DNA damage response and continues to provide crucial insights that explain how cells deal with genotoxic stress to avoid malignant transformation.

More recently, the intriguing phenomenon of cellular heterogeneity reached into the limelight as it became increasingly clear that significant variability exists between individual cells, even of the same genetic background and cell type. Single cells matter, for instance during cellular transformation or tumor relapse, and cellular variability thus impacts disease development and therapeutic outcome. Its determinants are surprisingly unexplored, however, and have not been studied in context of genome integrity maintenance.

The main objective of this project is to systematically assess cellular heterogeneity in genome integrity maintenance and characterize its causes and consequences. Quantitative automated high-content imaging of large cell cohorts will be used to identify hitherto unknown determinants of variability in the cellular responses to genotoxic stress and dissect at the single cell level the variability in (1) the chromatin response to DNA double-strand breaks, (2) the cellular response to replication stress, and (3) the cellular capacity to trigger phase transitions, a newly emerging mechanism of dynamic compartmentalization, at sites of genomic lesions. This project will bridge two thus far independently developed research fields (genome stability and cellular heterogeneity), reveal how cell-to-cell variation impacts cell fate and survival in response to genotoxic stress, and may uncover ways to homogenize this response for improved cancer therapies.

 Publications

year authors and title journal last update
List of publications.
2018 Matthias Altmeyer
Cells take a break when they are TIAR ed
published pages: , ISSN: 1469-221X, DOI: 10.15252/embr.201847403
EMBO reports 20/1 2019-11-22
2019 Sinan Kilic, Aleksandra Lezaja, Marco Gatti, Eliana Bianco, Jone Michelena, Ralph Imhof, Matthias Altmeyer
Phase separation of 53 BP 1 determines liquid‐like behavior of DNA repair compartments
published pages: , ISSN: 0261-4189, DOI: 10.15252/embj.2018101379
The EMBO Journal 38/16 2019-11-22
2019 Federico Teloni, Jone Michelena, Aleksandra Lezaja, Sinan Kilic, Christina Ambrosi, Shruti Menon, Jana Dobrovolna, Ralph Imhof, Pavel Janscak, Tuncay Baubec, Matthias Altmeyer
Efficient Pre-mRNA Cleavage Prevents Replication-Stress-Associated Genome Instability
published pages: 670-683.e12, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.11.036
Molecular Cell 73/4 2019-11-22
2018 Aleksandra Lezaja, Matthias Altmeyer
Inherited DNA lesions determine G1 duration in the next cell cycle
published pages: 24-32, ISSN: 1538-4101, DOI: 10.1080/15384101.2017.1383578
Cell Cycle 17/1 2019-05-06
2017 Stefania Pellegrino, Jone Michelena, Federico Teloni, Ralph Imhof, Matthias Altmeyer
Replication-Coupled Dilution of H4K20me2 Guides 53BP1 to Pre-replicative Chromatin
published pages: 1819-1831, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2017.05.016
Cell Reports 19/9 2019-05-06
2018 Michelena, Jone; Lezaja, Aleksandra; Teloni, Federico; Schmid, Thomas; Imhof, Ralph; Altmeyer, Matthias
Analysis of PARP inhibitor toxicity by multidimensional fluorescence microscopy reveals mechanisms of sensitivity and resistance
published pages: , ISSN: 2041-1723, DOI: 10.5167/uzh-152720
Nature Communications 2019-04-18
2018 Ina Klusmann, Kai Wohlberedt, Anna Magerhans, Federico Teloni, Jan O. Korbel, Matthias Altmeyer, Matthias Dobbelstein
Chromatin modifiers Mdm2 and RNF2 prevent RNA:DNA hybrids that impair DNA replication
published pages: 201809592, ISSN: 0027-8424, DOI: 10.1073/pnas.1809592115
Proceedings of the National Academy of Sciences 2019-04-18
2018 Sara Przetocka, Antonio Porro, Hella A. Bolck, Christina Walker, Aleksandra Lezaja, Anika Trenner, Christine von Aesch, Sarah-Felicitas Himmels, Alan D. D’Andrea, Raphael Ceccaldi, Matthias Altmeyer, Alessandro A. Sartori
CtIP-Mediated Fork Protection Synergizes with BRCA1 to Suppress Genomic Instability upon DNA Replication Stress
published pages: 568-582.e6, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.09.014
Molecular Cell 72/3 2019-04-18

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