Explore the words cloud of the chromo-SUMMIT project. It provides you a very rough idea of what is the project "chromo-SUMMIT" about.
The following table provides information about the project.
ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
|Coordinator Country||Switzerland [CH]|
|Total cost||1˙999˙815 €|
|EC max contribution||1˙999˙815 € (100%)|
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
|Duration (year-month-day)||from 2017-05-01 to 2022-04-30|
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|1||ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE||CH (LAUSANNE)||coordinator||1˙999˙815.00|
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.
|year||authors and title||journal||last update|
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
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|
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|
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 HP1Î±
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-02619-5
|Nature Communications 9/1||2019-04-18|
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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