IGBMC : Institut de la Génétique et de la Biologie Moléculaire et Cellulaire

• Researchers

  Adam BEN SHEM

  Dino MORAS

  Gabor PAPAI

  Arnaud POTERSZMAN

  Patrick SCHULTZ

• Post-Doctoral Fellows

  Olga KOLESNIKOVA

• PhD Students

  Alexandre FRECHARD

  Maximilien WERDERER

• Engineers & Technicians

  Corinne CRUCIFIX

  Sophie JACQUEMIN

  Simon PICHARD

  Danièle SPEHNER

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.

• 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 photoreceptors

  3. 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

• 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

• Publications

  • Structural Basis of Transcription: RNA Polymerase Backtracking and Its Reactivation.

    Abdelkareem M(1), Saint-Andre C(1), Takacs M(1), Papai G(1), Crucifix C(1), Guo X(1), Ortiz J(1), Weixlbaumer A(2).

    Mol Cell May 8, 2019 .

  • TFIIH: A multi-subunit complex at the cross-roads of transcription and DNA repair.

    Kolesnikova O(1), Radu L(1), Poterszman A(2).

    Adv Protein Chem Struct Biol 2019 ; 115:21-67 .

  • A revisited version of the apo structure of the ligand-binding domain of the human nuclear receptor retinoic X receptor alpha.

    Eberhardt J(1), McEwen AG(1), Bourguet W(2), Moras D(1), Dejaegere A(1).

    Acta Crystallogr F Struct Biol Commun Feb. 1, 2019 .

  • Molecular structure of promoter-bound yeast TFIID.

    Kolesnikova O(1)(2)(3)(4), Ben-Shem A(1)(2)(3)(4), Luo J(5), Ranish J(5), Schultz P(6)(7)(8)(9), Papai G(10)(11)(12)(13).

    Nat Commun Nov. 7, 2018 ; 9:4666 .

  • Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites.

    Di Mattia T(1)(2)(3)(4), Wilhelm LP(1)(2)(3)(4), Ikhlef S(5), Wendling C(1)(2)(3)(4), Spehner D(1)(2)(3)(4), Nomine Y(1)(2)(3)(4), Giordano F(6), Mathelin C(1)(2)(3)(4)(7), Drin G(5), Tomasetto C(8)(2)(3)(4), Alpy F(8)(2)(3)(4).

    EMBO Rep Jul 2018 ; 19:e45453 .

  • Structure-function analyses unravel distinct effects of allosteric inhibitors of HIV-1 integrase on viral maturation and integration.

    Bonnard D(1)(2), Le Rouzic E(3), Eiler S(4), Amadori C(3)(5), Orlov I(4), Bruneau JM(3), Brias J(3), Barbion J(3), Chevreuil F(3), Spehner D(4), Chasset S(3), Ledoussal B(3), Moreau F(3), Saib A(2), Klaholz BP(4), Emiliani S(5), Ruff M(6), Zamborlini A(7), Benarous R(8).

    J Biol Chem April 20, 2018 ; 293:6172-6186 .

  • Structural Basis for NusA Stabilized Transcriptional Pausing.

    Guo X(1), Myasnikov AG(1), Chen J(2), Crucifix C(1), Papai G(1), Takacs M(1), Schultz P(1), Weixlbaumer A(3).

    Mol Cell March 1, 2018 ; 69:816-827 .

  • Volta phase plate data collection facilitates image processing and cryo-EM structure determination.

    von Loeffelholz O(1), Papai G(1), Danev R(2), Myasnikov AG(1), Natchiar SK(1), Hazemann I(1), Menetret JF(1), Klaholz BP(3).

    J Struct Biol Jun 2018 ; 202:191-199 .

  • Structural features of the salivary gland hypertrophy virus of the tsetse fly revealed by cryo-electron microscopy and tomography.

    Orlov I(1), Drillien R(2), Spehner D(3), Bergoin M(4), Abd-Alla AMM(5), Klaholz BP(6).

    Virology Jan. 15, 2018 ; 514:165-169 .

  • Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1.

    Bednar J(1), Garcia-Saez I(2), Boopathi R(3), Cutter AR(4), Papai G(5), Reymer A(6), Syed SH(3), Lone IN(3), Tonchev O(3), Crucifix C(5), Menoni H(3), Papin C(7), Skoufias DA(2), Kurumizaka H(8), Lavery R(6), Hamiche A(9), Hayes JJ(10), Schultz P(11), Angelov D(12), Petosa C(13), Dimitrov S(14).

    Mol Cell May 4, 2017 ; 66:384-397 .

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