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

• Researchers

  Robert DRILLIEN

  Valérie LAMOUR

  Marc RUFF

• Post-Doctoral Fellows

  Julien BATISSE

  Eduardo BRUCH

• PhD Students

  Christophe LOTZ

• Engineers & Technicians

  Sylvia EILER

  Hélène MEYER

• 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

  • Publisher Correction: Post-translational modifications in DNA topoisomerase 2alpha highlight the role of a eukaryote-specific residue in the ATPase domain.

    Bedez C(1), Lotz C(1), Batisse C(1), Broeck AV(1), Stote RH(1), Howard E(2), Pradeau-Aubreton K(1), Ruff M(1), Lamour V(3)(4).

    Sci Rep July 10, 2018 ; 8:10673 .

  • Post-translational modifications in DNA topoisomerase 2alpha highlight the role of a eukaryote-specific residue in the ATPase domain.

    Bedez C(1), Lotz C(1), Batisse C(1), Broeck AV(1), Stote RH(1), Howard E(2), Pradeau-Aubreton K(1), Ruff M(1), Lamour V(3)(4).

    Sci Rep June 18, 2018 ; 8:9272 .

  • Unstable Protein Purification Through the Formation of Stable Complexes.

    Eiler S(1), Levy N(1), Maillot B(1), Batisse J(1), Aubreton KP(1), Oladosu O(1), Ruff M(2).

    Methods Mol Biol 2018 ; 1764:315-328 .

  • 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 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 .

  • Modulation of the functional association between the HIV-1 intasome and the nucleosome by histone amino-terminal tails.

    Benleulmi MS(1)(2), Matysiak J(1)(2), Robert X(3), Miskey C(4), Mauro E(1)(2), Lapaillerie D(1)(2)(5), Lesbats P(1)(2), Chaignepain S(6), Henriquez DR(7), Calmels C(1)(2)(5), Oladosu O(8), Thierry E(9), Leon O(7), Lavigne M(10)(11)(5), Andreola ML(1)(2)(5), Delelis O(9)(5), Ivics Z(4), Ruff M(8)(5), Gouet P(3)(5), Parissi V(12)(13)(14).

    Retrovirology Nov. 28, 2017 ; 14:54 .

  • The HIV-1 integrase-LEDGF allosteric inhibitor MUT-A: resistance profile, impairment of virus maturation and infectivity but without influence on RNA packaging or virus immunoreactivity.

    Amadori C(1)(2)(3)(4), van der Velden YU(5), Bonnard D(1), Orlov I(6), van Bel N(5), Le Rouzic E(1), Miralles L(7), Brias J(1), Chevreuil F(1), Spehner D(6), Chasset S(1), Ledoussal B(1), Mayr L(8), Moreau F(1), Garcia F(7), Gatell J(7), Zamborlini A(9), Emiliani S(2)(3)(4), Ruff M(6), Klaholz BP(6), Moog C(8), Berkhout B(10), Plana M(11), Benarous R(12)(13).

    Retrovirology Nov. 9, 2017 ; 14:50 .

  • Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration.

    Matysiak J(1)(2), Lesbats P(1)(2), Mauro E(1)(2), Lapaillerie D(1)(2)(3), Dupuy JW(4), Lopez AP(5), Benleulmi MS(1)(2)(3), Calmels C(1)(2)(3), Andreola ML(1)(2)(3), Ruff M(6), Llano M(5), Delelis O(7)(3), Lavigne M(8)(9)(3), Parissi V(10)(11)(12).

    Retrovirology July 28, 2017 ; 14:39 .

  • A User-Friendly DNA Modeling Software for the Interpretation of Cryo-Electron Microscopy Data.

    Lariviere D(1), Galindo-Murillo R(2), Fourmentin E(3), Hornus S(4), Levy B(4), Papillon J(5), Menetret JF(5), Lamour V(6)(7).

    Methods Mol Biol 2017 ; 1624:193-210 .

  • A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family.

    Okutman O(1)(2)(3), Muller J(4)(5), Skory V(1), Garnier JM(6), Gaucherot A(7), Baert Y(8), Lamour V(9), Serdarogullari M(10), Gultomruk M(10), Ropke A(11), Kliesch S(12), Herbepin V(13), Aknin I(14), Benkhalifa M(15), Teletin M(1), Bakircioglu E(16), Goossens E(8), Charlet-Berguerand N(7), Bahceci M(10), Tuttelmann F(11), Viville S(17)(18)(19)(20).

    J Assist Reprod Genet May 2017 ; 34:683-694 .

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