Integrated structural Biology
Architecture of nucleoprotein systems by 3-D Electron Microscopy
Our team deciphers the three-dimensional organization of macromolecular complexes by using high resolution cryo- Electron Microscopy (EM) to visualize single molecules in their native state and image analysis to extract signal from noise. We study how basal transcription factors interact with the promoter of protein-encoding genes and analyze the transmission of activation signals mediated by cis-acting transcription factors towards the basal transcription machinery in order to trigger increased transcription. The study of different intermediate states reveals snapshots of dynamic processes that highlight the conformational changes of these nanomachines during transcription initiation. These approaches were applied to several molecular systems including the SAGA and TFIID coactivators, but also to other systems such as TFIIH, TFIIE, RNA Polymerase I, DNA Topoisomerase II or HIV integrase, in collaboration mainly with IGBMC team leaders. As part of an integrated vision of cellular structural biology we analyze the organization of transcription within the nuclei of rod photoreceptors. The biological system used is a mouse model of a human disease: the type 7 Spinocerebellar Ataxia. Chromatin organization, histone modification and transcriptional activity were correlated in this context.
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Current projects
1. Transcription initiation and activation mechanisms
Improved structural model of TFIID
Mechanism of TFIID-mediated activated transcription
2. Transcription and nuclear architecture
Correlating transcription, histone modifications and chromatin structure in normal and SCA7 rod photoreceptors3. Integrated structural biology of rDNA transcription (Project leader : Dr Valérie Lamour)
4. DNA transposases (Project leader : Dr Valérie Lamour)
Functional and Structural studies of type II DNA topoisomerases associated with DNA and chemotherapeutic agents. -
Collaborations
F. Winston (Harvard medical school, Boston, USA). Structural study of the SAGA coactivator
PA. Weil (Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, USA) Structure of TFIID-containing transcription complexes
I. Berger (EMBL Grenoble), Structure of Taf sub complexes
Y Pommier (NIH Bethesda, USA). Structural characterization of human mitochondrial DNA Topoisomerase I (Valérie Lamour)
H. Tschochner (Regensburg University, Regensburg, Germany) Structure of RNA Polymerase I transcription initiation machinery. -
Prizes/Awards
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News
- Sept. 13, 2018 - 2017, a year with the CNRS in Alsace
- July 15, 2016 - Towards a better understanding of the molecular architecture of ribosomal RNA production machinery
- Jan. 6, 2013 - At the heart of transcription
- Dec. 6, 2010 - Myopathies, Research in progress : the desmine/myotubularine complexe offers new therapeutic hopes
- June 17, 2010 - The 3-dimensional transcription film
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Publications
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PLoS Negl Trop Dis July 22, 2019 ; 13:e0007591 .
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Structural Basis of Transcription: RNA Polymerase Backtracking and Its Reactivation.
Mol Cell July 25, 2019 ; 75:298-309 .
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TFIIH: A multi-subunit complex at the cross-roads of transcription and DNA repair.
Adv Protein Chem Struct Biol 2019 ; 115:21-67 .
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Acta Crystallogr F Struct Biol Commun Feb. 1, 2019 ; 75:98-104 .
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Molecular structure of promoter-bound yeast TFIID.
Nat Commun Nov. 7, 2018 ; 9:4666 .
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Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites.
EMBO Rep Jul 2018 ; 19:e45453 .
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J Biol Chem April 20, 2018 ; 293:6172-6186 .
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Structural Basis for NusA Stabilized Transcriptional Pausing.
Mol Cell March 1, 2018 ; 69:816-827 .
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Volta phase plate data collection facilitates image processing and cryo-EM structure determination.
J Struct Biol Jun 2018 ; 202:191-199 .
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Virology Jan. 15, 2018 ; 514:165-169 .
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Job opportunities
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Alumni
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