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DiVineGenoMe SIGNED

Decoding cell-to-cell variation in genome integrity maintenance

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

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.

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

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 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.	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

List of publications.
year	authors and title	journal	last update
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 liquidâ€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. Dâ€™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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