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chromo-SUMMIT SIGNED

Decoding dynamic chromatin signaling by single-molecule multiplex detection

Total Cost €

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EC-Contrib. €

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Partnership

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 chromo-SUMMIT project word cloud

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

cancer    underlying    implicated    outcomes    remodel    encoded    deposit    single    molecular    dynamically    transient    interact    library    models    thereby    interventions    recognition    ddr    repair    critically    sampling    therapeutic    broad    interaction    libraries    chemically    critical    fiber    identification    utmost    decoding    observe    effector    flow    damage    situ    modifications    network    supramolecular    signaling    function    nucleoprotein    multiplex    mechanisms    organizing    effectors    synthesize    modification    biomedical    dynamic    immobilized    propagate    biochemistry    integrate    chemistry    subsequent    fibers    time    generate    biological    dissect    central    multivalent    combinations    interactions    employ    ptms    fundamental    complexity    regulates    cell    computational    protein    reveal    arrays    post    detection    molecule    survival    peptide    chromatin    outside    dna    structure    cascades    chemical    combinational    ptm    genome    culture    translational    designer    polony    yield    regulated    imaging   

Project "chromo-SUMMIT" data sheet

The following table provides information about the project.

Coordinator
ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE 

Organization address
address: BATIMENT CE 3316 STATION 1
city: LAUSANNE
postcode: 1015
website: www.epfl.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˙999˙815 €
 EC max contribution 1˙999˙815 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-05-01   to  2022-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE CH (LAUSANNE) coordinator 1˙999˙815.00

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 Project objective

Transient multivalent interactions are critical for biological processes such as signaling pathways controlling chromatin function. Chromatin, the nucleoprotein complex organizing the genome, is dynamically regulated by post-translational modifications (PTMs) of the chromatin fiber. Protein effectors interact with combinations of these PTMs through multivalent interactions, deposit novel PTMs, thereby propagate signaling cascades and remodel chromatin structure. To reveal the underlying molecular mechanisms, methods outside classical biochemistry are required, in particular due to the combinational complexity of chromatin PTMs and the transient supramolecular interactions crucial for their recognition. Here, we develop a novel approach, where we synthesize arrays of chemically defined designer chromatin fibers and use dynamic multiplex single-molecule imaging to dissect multivalent signaling processes in chromatin. Our studies target a key pathway, the DNA damage response (DDR), which regulates DNA repair processes central to cell survival and is critically implicated in cancer. Detailed knowledge is of utmost importance to develop targeted therapeutic interventions. We thus employ advanced peptide and protein chemistry to generate libraries of chromatin fibers of a defined PTM state that is encoded in the chromatin DNA. With the library immobilized in a flow cell, we use single-molecule detection to directly observe signaling processes by key DDR effectors in real time. Subsequent in situ polony decoding allows the identification of each chromatin fiber’s modification state, enabling broad sampling of signaling outcomes. Finally, we use dynamic computational models to integrate the effector-chromatin interaction network and test key mechanisms in cancer-based cell culture. Together, these methods will yield fundamental insight into chromatin and DDR signaling and will be of broad use for chemical and biomedical research with applications beyond the chromatin field.

 Publications

year authors and title journal last update
List of publications.
2019 Maxime Mivelaz, Anne-Marinette Cao, Slawomir Kubik, Sevil Zencir, Ruud Hovius, Iuliia Boichenko, Anna Maria Stachowicz, Christoph F. Kurat, David Shore, Beat Fierz
Chromatin Fiber Invasion and Nucleosome Displacement by the Rap1 Transcription Factor
published pages: , ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.10.025
Molecular Cell 2019-12-16
2019 Beat Fierz, Michael G. Poirier
Biophysics of Chromatin Dynamics
published pages: 321-345, ISSN: 1936-122X, DOI: 10.1146/annurev-biophys-070317-032847
Annual Review of Biophysics 48/1 2019-11-08
2019 Iuliia Boichenko, Beat Fierz
Chemical and biophysical methods to explore dynamic mechanisms of chromatin silencing
published pages: 1-10, ISSN: 1367-5931, DOI: 10.1016/j.cbpa.2019.01.022
Current Opinion in Chemical Biology 51 2019-11-08
2018 Sinan Kilic, Suren Felekyan, Olga Doroshenko, Iuliia Boichenko, Mykola Dimura, Hayk Vardanyan, Louise C. Bryan, Gaurav Arya, Claus A. M. Seidel, Beat Fierz
Single-molecule FRET reveals multiscale chromatin dynamics modulated by HP1α
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-02619-5
Nature Communications 9/1 2019-04-18
2018 Sinan Kilic, Iuliia Boichenko, Carolin C. Lechner, Beat Fierz
A bi-terminal protein ligation strategy to probe chromatin structure during DNA damage
published pages: 3704-3709, ISSN: 2041-6520, DOI: 10.1039/c8sc00681d
Chemical Science 9/15 2019-04-18

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