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

• Researchers

  Robert DRILLIEN

  Valérie LAMOUR

  Marc RUFF

• Post-Doctoral Fellows

  Julien BATISSE

  Benoît MAILLOT

  Karine PRADEAU AUBRETON

• Phd Students

  Christophe LOTZ

  Oyindamola OLADOSU

  Arnaud VANDEN BROECK

• Engineers & Technicians

  Sylvia EILER

  Betty ORY

• Collaborateur Occasionnel

  Nicolas LEVY

Integrated structural Biology

Chromatin stability and DNA mobility

Cellular Macromolecular Complexes of Retroviral Integrases and DNA Topoisomerases

Our research group focuses on the molecular mechanisms governing nucleic acid transport, processing and topological changes of chromatin DNA. Our present targets are nucleoprotein complexes involved in retroviral DNA integration and eukaryotic DNA topoisomerases. We integrate structural data from high resolution (X-ray crystallography), medium resolution (CryoEM) and low resolution (cell imaging) with in vitro and in cellulo functional data.
The main focus of Marc Ruff is to understand the molecular processes performed by the HIV pre-integration complexes (PIC). The aim is to provide a four dimensional view of the PIC, from reverse transcription until integration. A second component of the project focuses on drug design aspects to optimize protein-protein interaction and conformational inhibitors.
Valérie Lamour’s project is aiming at the functional and structural studies of DNA topoisomerase cellular complexes targeted by therapeutic compounds used in cancer and anti-bacterial therapies. The main goal of this study is to identify and study the structure/function of Topoisomerase-associated complexes targeted by drugs through a combination of proteomic and structural approaches.

• Current projects

  • The HIV pre-integration complex maturation in the cytoplasm
  • Nuclear transfer of the HIV pre-integration complex
  • HIV pre-integration complex chromatin targeting and nucleosome interactions
  • Molecular mechanisms of the HIV genome integration
  • bacterial DNA gyrase complexes
  • identification and structural studies of human type 2 DNA topoisomerases complexes

• Collaborations

  • Sarah Cianferani (Bio-organic Mass Spectrometry Laboratory, UDS, Cronembourg)
  • Stéphane Emiliani (Infection Diseases Department, Cochin Institute, Paris)
  • Yves Mely (Laboratory of Biophotonics and Pharmacology, UDS, Illkirch)
  • François Moreau and Richard Benarous (Mutabilis company)
  • Vincent Parissi (Fundamental Microbiology and Pathogenicity, University of Bordeaux 2)
  • Pr. Yves Pommier  (NIH Bethesda, USA)
  • Noëlle Potier (Laboratoire de spectrométrie de masse, Institut de Chimie de Strasbourg)
  • Alain Wagner (Laboratoire des systèmes chemo-fonctionnels, Faculté de Pharmacie de Strasbourg ) 

• Prizes/Awards

• News

  • March 29, 2016 - Production of unstable proteins through the formation of stable core complexes

• Publications

  • DNA minicircles clarify the specific role of DNA structure on retroviral integration.

    Pasi M(1), Mornico D(2), Volant S(2), Juchet A(3), Batisse J(4), Bouchier C(5), Parissi V(6), Ruff M(4), Lavery R(1), Lavigne M(7).

    Nucleic Acids Res July 20, 2016 .

  • Production of unstable proteins through the formation of stable core complexes.

    Levy N(1), Eiler S(1), Pradeau-Aubreton K(1), Maillot B(1), Stricher F(1), Ruff M(1).

    Nat Commun March 17, 2016 ; 7:10932 .

  • Intasome architecture and chromatin density modulate retroviral integration into nucleosome.

    Benleulmi MS, Matysiak J, Henriquez DR, Vaillant C, Lesbats P, Calmels C, Naughtin M, Leon O, Skalka AM, Ruff M, Lavigne M, Andreola ML, Parissi V.

    Retrovirology Feb. 7, 2015 ; 12:13 .

  • Site-Selective Monitoring of the Interaction of the SRA Domain of UHRF1 with Target DNA Sequences Labeled with 2-Aminopurine.

    Greiner VJ(1), Kovalenko L(1,)(2), Humbert N(1), Richert L(1), Birck C(3), Ruff M(3), Zaporozhets OA(2), Dhe-Paganon S(4), Bronner C(1,)(3), Mély Y(1).

    Biochemistry Oct. 6, 2015 ; 54:6012-20 .

  • DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity.

    Naughtin M(1), Haftek-Terreau Z(1), Xavier J(1), Meyer S(2), Silvain M(3), Jaszczyszyn Y(3), Levy N(4), Miele V(5), Benleulmi MS(6), Ruff M(4), Parissi V(6), Vaillant C(7), Lavigne M(8).

    PLoS One June 15, 2015 ; 10:e0129427 .

  • Chemical cross-linking and mass spectrometry to determine the subunit interaction network in a recombinant human SAGA HAT subcomplex.

    Nguyen-Huynh NT(1), Sharov G(2), Potel C(1), Fichter P(2), Trowitzsch S(3), Berger I(3), Lamour V(2), Schultz P(2), Potier N(1), Leize-Wagner E(1).

    Protein Sci Aug 2015 ; 24:1232-46 .

  • Live cell immunogold labelling of RNA polymerase II.

    Orlov I(1), Schertel A(2), Zuber G(3), Klaholz B(1), Drillien R(1), Weiss E(4), Schultz P(1), Spehner D(1).

    Sci Rep Feb. 9, 2015 ; 5:8324 .

  • [Structural insight into negative DNA supercoiling by DNA gyrase, a bacterial type 2A DNA topoisomerase].

    Papillon J(1), Ménétret JF(1), Batisse C(1), Hélye R(2), Schultz P(1), Potier N(2), Lamour V(3).

    Med Sci (Paris) Dec 2014 ; 30:1081-4 .

  • KAY-2-41, a novel nucleoside analogue inhibitor of orthopoxviruses in vitro and in vivo.

    Duraffour S(1), Drillien R, Haraguchi K, Balzarini J, Topalis D, van den Oord JJ, Andrei G, Snoeck R.

    Antimicrob Agents Chemother 2014 ; 58:27-37 .

  • HSPA8/HSC70 chaperone protein: structure, function, and chemical targeting.

    Stricher F(1), Macri C, Ruff M, Muller S.

    Autophagy Dec 2013 ; 9:1937-54 .

  See all publications=>

• Job opportunities

  • Etudes Fonctionnelles Et Structurales Des Complexes Des Adn Topoisomérases Humaines Avec Des Molécules Utilisées En Chimiothérapie Des Cancers (H/F)
  • Études Fonctionnelles Et Structurales Des Complexes De Pré-Intégration Rétroviraux (H/F)

• Videos

• Thesis subjects

  • Etudes Fonctionnelles Et Structurales Des Complexes Des Adn Topoisomérases Humaines Avec Des Molécules Utilisées En Chimiothérapie Des Cancers (H/F)
  • Études Fonctionnelles Et Structurales Des Complexes De Pré-Intégration Rétroviraux (H/F)