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

• Researchers

  Isabelle BILLAS MASSOBRIO

  Bruno KLAHOLZ

  Kundhavai NATCHIAR

  Alexandre OURJOUMTSEV

• Post-Doctoral Fellows

  Jaime ALEGRIO LOURO

  Brice BEINSTEINER

  Vanessa DACLEU SIEWE

  Clara Ottilie LOEFFELHOLZ VON COLBERG

  Kareem MOHIDEEN ABDUL

  Rachel TABARONI

• PhD Students

  Léo FRECHIN

  Pierre VILELA

• Engineers & Technicians

  Leonid ANDRONOV

  Isabelle HAZEMANN

  Jean-François MENETRET

Integrated structural Biology

Large complexes involved in gene expression

Transcription and translation are fundamental molecular mechanisms of gene activity regulation with profound implications for human health. The ligand-dependent transcriptional regulation by nuclear receptors bound to DNA response elements involves the transient assembly of large co-regulator complexes. These trigger chromatin remodeling and facilitate the assembly of the general transcription machinery on the promoter of the target gene. Gene expression is also regulated at the level of protein synthesis, for example, by protein factors that bind to the ribosome during the translation initiation, elongation and termination phase. The initiation phase is strongly regulated by factors and also by the mRNA itself and well-characterized reaction intermediates of the initiating ribosomal nano-machinery are potential targets for antibiotics. Both transcription and translation complexes represent large, transient macromolecular assemblies that we investigate by using an integrative structural biology approach with crystallography and cryo-electron microscopy forming the core.

Bruno Klaholz is also scientific coordinator of the Biostructure structural biology research infrastructure, itself selected within the FRISBI project.

 Know more about the cryo electron microscopy facilities

Movie: Visualization of modifications in the human ribosome structure, a new feat for cryo electron microscopy

• Current projects

• Collaborations

• Prizes/Awards

  • Bruno Klaholz - Médaille d'Argent - CNRS - 2018
  • Bruno Klaholz - Raimond Castaing Prize - French Society of Microscopies - 2017
  • Bruno KLAHOLZ - Richard Lounsbery prize - Académie des sciences - 2016
  • Bruno KLAHOLZ - ERC Starting grant - European Research Council (ERC) - 2009
  • Bruno KLAHOLZ - Nuclear Receptor Conference Presentation Prize - European Molecular Biology Organization (EMBO) - 2009
  • Bruno KLAHOLZ - Bronze Medal - CNRS - 2008
  • Bruno KLAHOLZ - Paul Mandel Gutenberg Group Prize - CNRS - 2008
  • Bruno Klaholz - EMBO Young Investigator Award - European Molecular Biology Organization Young Investigator Programme (EMBO YIP) - 2006

• News

  • Sept. 13, 2018 - 2017, a year with the CNRS in Alsace
  • Nov. 15, 2017 - Visualization of modifications in the human ribosome structure, a new feat for cryo electron microscopy
  • April 22, 2015 - The fine structure of the human ribosome unveiled!
  • Nov. 7, 2014 - Focus on helical polyribosomes
  • June 19, 2014 - Interplay of symmetry and asymmetry in a nuclear receptor
  • Sept. 24, 2013 - Integrated approach in structural biology: initiation factor IF2 from every angle
  • Feb. 23, 2012 - Official launching of the ESFRI integrative structural biology infrastructure : INSTRUCT
  • Jan. 17, 2012 - First complete 3D mapping of vitamin D receptor

• Publications

  • Targeting the Human 80S Ribosome in Cancer: From Structure to Function and Drug Design for Innovative Adjuvant Therapeutic Strategies.

    Gilles A(1), Frechin L(2), Natchiar K(2), Biondani G(3), Loeffelholz OV(2), Holvec S(2), Malaval JL(1), Winum JY(1), Klaholz BP(2), Peyron JF(3).

    Cells March 5, 2020 .

  • Including crystallographic symmetry in quantum-based refinement: Q|R#2.

    Zheng M(1), Biczysko M(1), Xu Y(1), Moriarty NW(2), Kruse H(3), Urzhumtsev A(4), Waller MP(5), Afonine PV(2).

    Acta Crystallogr D Struct Biol Jan. 1, 2020 .

  • Corrigendum to "Cryo-EM Structure (4.5 A) of Yeast Kinesin-5-Microtubule Complex Reveals a Distinct Binding Footprint and Mechanism of Drug Resistance" [J. Mol. Biol. 431 (2019) 864-872] https://doi.org/10.1016/j.jmb.2019.01.011.

    von Loeffelholz O(1), Pena A(2), Drummond DR(3), Cross R(4), Moores CA(5).

    J Mol Biol Nov. 15, 2019 .

  • Deriving and refining atomic models in crystallography and cryo-EM: the latest Phenix tools to facilitate structure analysis.

    Klaholz BP(1).

    Acta Crystallogr D Struct Biol Oct. 1, 2019 .

  • CENP-A nucleosome clusters form rosette-like structures around HJURP during G1.

    Andronov L(1)(2)(3)(4)(5), Ouararhni K(2)(3)(4)(5)(6), Stoll I(2)(3)(4)(5)(6), Klaholz BP(7)(8)(9)(10)(11), Hamiche A(12)(13)(14)(15)(16).

    Nat Commun Sept. 30, 2019 ; 10:4436 .

  • Mask-based approach to phasing of single-particle diffraction data. II. Likelihood-based selection criteria.

    Lunin VY(1), Lunina NL(1), Petrova TE(1), Baumstark MW(2), Urzhumtsev AG(3).

    Acta Crystallogr D Struct Biol Jan. 1, 2019 ; 75:79-89 .

  • eIF2B-catalyzed nucleotide exchange and phosphoregulation by the integrated stress response.

    Kenner LR(1), Anand AA(1)(2), Nguyen HC(1), Myasnikov AG(1)(3), Klose CJ(1)(2), McGeever LA(1)(2), Tsai JC(1)(2), Miller-Vedam LE(1), Walter P(4)(2), Frost A(4)(5).

    Science May 3, 2019 ; 364:491-495 .

  • Activation of the Endonuclease that Defines mRNA 3' Ends Requires Incorporation into an 8-Subunit Core Cleavage and Polyadenylation Factor Complex.

    Hill CH(1), Boreikaite V(1), Kumar A(1), Casanal A(1), Kubik P(1), Degliesposti G(1), Maslen S(1), Mariani A(1), von Loeffelholz O(2), Girbig M(1), Skehel M(1), Passmore LA(3).

    Mol Cell March 21, 2019 ; 73:1217-1231 .

  • Publisher Correction: N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation.

    Ma H(1)(2)(3), Wang X(4), Cai J(5), Dai Q(2)(3), Natchiar SK(6), Lv R(1), Chen K(2)(3), Lu Z(2)(3), Chen H(1), Shi YG(1)(7), Lan F(1), Fan J(5), Klaholz BP(6), Pan T(8), Shi Y(9)(10), He C(11)(12)(13).

    Nat Chem Biol May 15, 2019 ; 15:549 .

  • N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation.

    Ma H(1)(2)(3), Wang X(4), Cai J(5), Dai Q(2)(3), Natchiar SK(6), Lv R(1), Chen K(2)(3), Lu Z(2)(3), Chen H(1), Shi YG(1)(7), Lan F(1), Fan J(5), Klaholz BP(6), Pan T(8), Shi Y(9)(10), He C(11)(12)(13).

    Nat Chem Biol Jan 2019 ; 15:88-94 .

  See all publications=>

• Job opportunities

• Alumni

• Videos

  • Video human ribosome

• Thesis subjects

  • Etude Structure-Fonction Du Ribosome Humain (H/F)
  • The Study Of The Molecular Basis Of The Crosstalk Between The Glucocorticoid Receptor And Physiological Partners Offers Perspectives In The Development Of Novel Anti-Inflammatory Therapeutics (H/F)