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ChromArch SIGNED

Single Molecule Mechanisms of Spatio-Temporal Chromatin Architecture

Total Cost €

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EC-Contrib. €

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Partnership

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Project "ChromArch" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAET ULM 

Organization address
address: HELMHOLTZSTRASSE 16
city: ULM
postcode: 89081
website: www.uni-ulm.de

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 Germany [DE]
 Project website http://www.uni-ulm.de/nawi/nawi-biophys/forschung/forschung-gebhardt/horizon-2020/
 Total cost 1˙486˙578 €
 EC max contribution 1˙486˙578 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-05-01   to  2021-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAET ULM DE (ULM) coordinator 1˙486˙578.00

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 Project objective

Chromatin packaging into the nucleus of eukaryotic cells is highly sophisticated. It not only serves to condense the genomic content into restricted space, but mainly to encode epigenetic traits ensuring temporally controlled and balanced transcription of genes and coordinated DNA replication and repair. The non-random three-dimensional chromatin architecture including looped structures between genomic control elements relies on the action of architectural proteins. However, despite increasing interest in spatio-temporal chromatin organization, mechanistic details of their contributions are not well understood.

With this proposal I aim at unveiling molecular mechanisms of protein–mediated chromatin organization by in vivo single molecule tracking and quantitative super-resolution imaging of architectural proteins using reflected light sheet microscopy (RLSM). I will measure the interaction dynamics, the spatial distribution and the stoichiometry of architectural proteins throughout the nucleus and at specific chromatin loci within single cells. In complement single molecule force spectroscopy experiments using magnetic tweezers (MT), I will study mechanisms of DNA loop formation in vitro by structure-mediating proteins.

Integrating these spatio-temporal and mechanical single molecule information, I will in the third sup-project measure the dynamics of relative end-to-end movements and the forces acting within a looped chromatin structure in living cells.

Taken together, my experiments will greatly enhance our mechanistic understanding of three-dimensional chromatin architecture and inspire future experiments on its regulatory effects on nuclear functions and potential therapeutic utility upon controlled modification.

 Publications

year authors and title journal last update
List of publications.
2020 A. Große-Berkenbusch, J. Hettich, T. Kuhn, N. Fili, A.W. Cook, Y. Hari-Gupta, A. Palmer, L. Streit, P.J.I. Ellis, C.P. Toseland* and J.C.M. Gebhardt
Myosin VI moves on nuclear actin filaments and supports long-range chromatin rearrangements
published pages: , ISSN: , DOI: 10.1101/2020.04.03.023614
bioRxiv 2020-04-15
2019 Johannes Hettich, J. Christof M. Gebhardt
Computer aided interactive gene network simulations including stochastic molecular kinetics and noise
published pages: , ISSN: , DOI: 10.1101/872374
bioRxiv 2020-01-14
2017 Karen Clauß, Achim P. Popp, Lena Schulze, Johannes Hettich, Matthias Reisser, Laura Escoter Torres, N. Henriette Uhlenhaut, J. Christof M. Gebhardt
DNA residence time is a regulatory factor of transcription repression
published pages: 11121-11130, ISSN: 0305-1048, DOI: 10.1093/nar/gkx728
Nucleic Acids Research 45/19 2019-09-02
2018 Matthias Reisser, Anja Palmer, Achim P. Popp, Christopher Jahn, Gilbert Weidinger, J. Christof M. Gebhardt
Single-molecule imaging correlates decreasing nuclear volume with increasing TF-chromatin associations during zebrafish development
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-07731-8
Nature Communications 9/1 2019-09-02
2017 Harsha Agarwal, Matthias Reisser, Celina Wortmann, J. Christof M. Gebhardt
Direct Observation of Cell-Cycle-Dependent Interactions between CTCF and Chromatin
published pages: 2051-2055, ISSN: 0006-3495, DOI: 10.1016/j.bpj.2017.04.018
Biophysical Journal 112/10 2019-09-02
2018 J. Hettich, J.C.M. Gebhardt
Transcription factor target site search and gene regulation in a background of unspecific binding sites
published pages: , ISSN: 0022-5193, DOI: 10.1016/j.jtbi.2018.05.037
Journal of Theoretical Biology 2019-09-02
2018 Rahel Stefanie Wiehe, Boris Gole, Laurent Chatre, Paul Walther, Enrico Calzia, Anja Palmer, J. Christof M. Gebhardt, Miria Ricchetti, Lisa Wiesmüller
Correction: Endonuclease G promotes mitochondrial genome cleavage and replication
published pages: , ISSN: 1949-2553, DOI: 10.18632/oncotarget.25645
Oncotarget 9/45 2019-09-02
2019 Mahé Raccaud, Elias T. Friman, Andrea B. Alber, Harsha Agarwal, Cédric Deluz, Timo Kuhn, J. Christof M. Gebhardt, David M. Suter
Mitotic chromosome binding predicts transcription factor properties in interphase
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-08417-5
Nature Communications 10/1 2019-09-02
2018 Lisa Hipp, Judith Beer, Oliver Kuchler, Matthias Reisser, Daniela Sinske, Jens Michaelis, J. Christof M. Gebhardt, Bernd Knöll
Single-molecule imaging of the transcription factor SRF reveals prolonged chromatin-binding kinetics upon cell stimulation
published pages: 201812734, ISSN: 0027-8424, DOI: 10.1073/pnas.1812734116
Proceedings of the National Academy of Sciences 2019-09-02
2019 Matthias Reisser, Johannes Hettich, Timo Kuhn, J. Christof M. Gebhardt
Inferring quantity and qualities of superimposed reaction rates in single molecule survival time distributions
published pages: , ISSN: , DOI: 10.1101/679258
bioRxiv 2019-09-02

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