Institute of Chemistry & Biology of Membranes & Nano-objects • Bordeaux

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Internal CBMN Seminar : newcomers in CBMN, 17th of January, 2pm Internal CBMN Seminar: A. Simon, 6 Dec. 2018 Marisela Velez, 28 november 2018, 2pm, IECB Marc Bramkamp, 16 november 2018, 2pm, IECB Kazushi Kinbara, 12 november 2018, 11am, IECB Internal CBMN Seminar: J. Lang, 8 November 2018 Internal CBMN Seminars: A. Baudin, 6 September 2018 Plateforme production de protéines, 5 juillet 2018, 14h, ENSTBB Patrick Trouillas, 21 June 2018, 2pm, ENSCBP Lucie Khemtemourian, 21 June 2018, 11am, IECB Jonathan Faherty, 7th June, 11 AM, IECB Yann Fichou, 3 May 2018, 2pm, IECB Internal CBMN seminars: A. Ciaccafava and G. Compain, 5 April 2018 Alain Roussel, 29/03/2018, 4 pm, ENSCBP Simon Poly, 22 march 2018, 2pm, ENSCBP J.Crassous, M. Sallé & A. Martinez, 18/12/2017, 10 am, IECB O.Reinaud & V. Artero, 7/12/2017, 10 am, IECB R. Dos santos Morais, 30/11/2017, 4 PM, ENSCBP Christian Griesinger, November 24th, 11am, IECB Takahiro Muraoka, 16/11/2017, 11am, ENSCBP Vladimir Torbeev, 9/11/2017, 2pm, ENSCBP M. D. Smith & T.Constantieux, 3/11/2017, 2h30 pm, IECB James Nowick, 15 september 2017, 11am, IECB Emmanuelle Thinon, 28 June 2017, 11 am, IECB Caroline Tokarski, 15 June 2017, 4pm, ENSCBP Christian Salesse, 8 June 2017, 4pm, ENSCBP Patrice Rey, 01 June 2017, 2h30 pm, ENSCBP Christina Sizun, 18 May 2017, 4 pm, ENSCBP Marisela Velez, 5 May 2017, 11am, IECB Iqbal Choudhary, 27 April 2017, 4 pm, ENSCBP Vincent Aucagne, 21 April 2017, 11 am, IECB Sophie Zinn-Justin, 14 April 2017, 11 am, IECB Cécile Feuillie, 16 February 2017, 4 PM, ENSCBP Félix M. Goñi, 8 december 2016, 4 pm, ENSCBP Félix M. Goñi, 17 november 2016, 4 pm, ENSCBP Carl Creutz, 20 october 2016, 4 pm, ENSCBP Diego Romero, 30 september 2016, 11 am, IECB A. Ciaccafava, 8 september 2016, 14h, ENSCBP A. Ramamoorthy, 16 June 2016, 16h, ENSCBP Alexandre de Brevern, 2 june 2016, ENSCBP Isabelle Landrieu, 26 May, 16h, ENSCBP Frances Sepavoric, 12 May, 16h, ENSCBP Thomas Pradeu, 7 April 2016, 9h, ENSCBP Françoise Argoul, 3 march 2016, 16h, ENSCBP Corinne Loutelier-Bourhis, 16/12/2015, 16h Aristotelis XENAKIS, 3 december 2015, 16h Fabian Kiessling, 26 november 2015, 11h Michaël Molinari, 20 november 2015, 11h Dipankar Das Sarma, 28 October 2015, 14h. Olivier Donard, 22 october 2015, 16h, ENSCBP E. Morvan & A.Grelard, 17/12/2015, 16h, ENSCBP Christophe Cullin, 10 september 2015, 14 h Brigitte Lindet, 18 June 2015, 16h, ENSCBP(B) Marion Decossas, 4 June 2015, 16h, ENSCBP(B) Pascale Schellenberger, 21 Mai 2015, 16h F. Leal-Calderon, 7 May 2015, 16h, ENSCBP(B) Ibrahim Abdulhalim, 9 April 2015, 14h, ENSCBP Manon Carré, 26 March 2015, 14h, ENSCBP(B) C. Bure & JM Schmitter, 19 March 2015, 16h T. Ogata & H. Ihara, 17 March 2015, 11h, IECB Banafshe Larijani, 12 March 2015, 16h, ENSCBP
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Internal CBMN Seminar : newcomers ... Internal CBMN Seminar: A. Simon, 6 ... Marisela Velez, 28 november 2018, 2... Marc Bramkamp, 16 november 2018, 2p... Kazushi Kinbara, 12 november 2018, ... Internal CBMN Seminar: J. Lang, 8 N... Internal CBMN Seminars: A. Baudin, ... Plateforme production de protéine... Patrick Trouillas, 21 June 2018, 2p... Lucie Khemtemourian, 21 June 2018, ... Jonathan Faherty, 7th June, 11 AM, ... Yann Fichou, 3 May 2018, 2pm, IECB Internal CBMN seminars: A. Ciaccafa... Alain Roussel, 29/03/2018, 4 pm, EN... Simon Poly, 22 march 2018, 2pm, ENS... J.Crassous, M. Sallé & A. Martinez... O.Reinaud & V. Artero, 7/12/2017, 1... R. Dos santos Morais, 30/11/2017, 4... Christian Griesinger, November 24th... Takahiro Muraoka, 16/11/2017, 11am,... Vladimir Torbeev, 9/11/2017, 2pm, E... M. D. Smith & T.Constantieux, 3/11/... James Nowick, 15 september 2017, 11... Emmanuelle Thinon, 28 June 2017, 11... Caroline Tokarski, 15 June 2017, 4p... Christian Salesse, 8 June 2017, 4pm... Patrice Rey, 01 June 2017, 2h30 pm,... Christina Sizun, 18 May 2017, 4 pm,... Marisela Velez, 5 May 2017, 11am, I... Iqbal Choudhary, 27 April 2017, 4 p... Vincent Aucagne, 21 April 2017, 11 ... Sophie Zinn-Justin, 14 April 2017, ... Cécile Feuillie, 16 February 2017,... Félix M. Goñi, 8 december 2016, 4... Félix M. Goñi, 17 november 2016, ... Carl Creutz, 20 october 2016, 4 pm,... Diego Romero, 30 september 2016, 11... A. Ciaccafava, 8 september 2016, 14... A. Ramamoorthy, 16 June 2016, 16h,... Alexandre de Brevern, 2 june 2016, ... Isabelle Landrieu, 26 May, 16h, ENS... Frances Sepavoric, 12 May, 16h, ENS... Thomas Pradeu, 7 April 2016, 9h, EN... Françoise Argoul, 3 march 2016, 1... Corinne Loutelier-Bourhis, 16/12/20... Aristotelis XENAKIS, 3 december 201... Fabian Kiessling, 26 november 2015,... Michaël Molinari, 20 november 2015... Dipankar Das Sarma, 28 October 2015... Olivier Donard, 22 october 2015, 16... E. Morvan & A.Grelard, 17/12/2015, ... Christophe Cullin, 10 september 201... Brigitte Lindet, 18 June 2015, 16h,... Marion Decossas, 4 June 2015, 16h, ... Pascale Schellenberger, 21 Mai 2015... F. Leal-Calderon, 7 May 2015, 16h, ... Ibrahim Abdulhalim, 9 April 2015, 1... Manon Carré, 26 March 2015, 14h, ... C. Bure & JM Schmitter, 19 March 20... T. Ogata & H. Ihara, 17 March 2015,... Banafshe Larijani, 12 March 2015, 1...
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Patricia DULOR Anthony BOUTER Olivier LAMBERT Jochen LANG Pascale SUBRA-PATERNAULT Maria URDACI Marie-Christine DURRIEU Xavier SANTARELLI Gilles GUICHARD Yann FERRAND Isabelle BESTEL Juan ELEZGARAY Antoine LOQUET Sophie LECOMTE Reiko ODA Marc BONNEU

Structure and Activity of biological Macromolecules

     

 

Research activities in the group aim at understanding biological processes and their mechanistic aspects based on the 3-dimensional atomic structure of biological macromolecules or assemblies. Use of X-ray crystallography as a major tool coupled to different biochemical and biological techniques is made. Current interests include:

     -    Enzymes and metabolic pathways,
     -    Recognition of protein surfaces by foldamers,
     -    Proteins of therapeutic interest.

 

 

Enzymes and Metabolic pathways:

Most of the enzymes that control each step of the flavonoid biosynthetic pathway have been identified from a molecular and biochemical point of view. Nevertheless, little is known about the structural and mechanistic properties of enzymes which catalyze the last steps of the pathway leading to anthocyanins and proanthocyanidins, two major classes of compounds known to contribute to the organoleptic properties of many plant products and to have beneficial effects on human health.

 

Structural investigations at atomic resolution, together with binding-equilibrium and kinetic studies, constitute useful tools to elucidate how enzymes work in the context of molecular pathways in the cell. Current investigations concern enzymes such as dyhydroflavonol 4-reductase (DFR), anthocyanidin and leucoanthocyanidin reductases, anthocyanin synthase and others from Vitis vinefera.

 

    Collaborations:

    -   Pr S. Delrot, ISVV, Villenave d’Ornon (France),
    -   Pr S. Antonczak, Université de Nice Sophia Antipolis (France).

 

 

In a similar way, we contribute to the investigation of secondary metabolite pathways in model aromatic plants (sweet basil, turmeric and ginger). Enzymes under investigation are curcuma synthases, polyketide synthases and double bond reductases involved in the biosynthesis of curcuminoids and gingerols.

 

    Collaboration:

      -  Dr D.R. Gang, Institute of Biological Chemistry, Washington State University (USA).

 

 

Recognition of protein surfaces by foldamers:

 Protein-protein interactions are a central issue in biological processes, and represent relevant therapeutic targets for the treatment of many diseases. The design of antagonistic molecules directed towards the disruption of these interactions requires the specific recognition of relevant protein surfaces. Aromatic oligomers present all the properties (high functionalization, stability and easy predictability of the structure, length flexibility) to reach that point.

In collaboration with Ivan Huc’s group(*) (who gained large expertise in the biosynthesis of quinoline derived oligoamide foldamers), we are particularly interested in validating a novel approach based on combining covalent attachment and structural characterization to decorate a foldamer with proteinogenic side chains, so that it can bind a given protein surface. Key preliminary results have been obtained using human carbonic anhydrase II. This enzyme was selected as a model system because it crystallizes easily, and it binds inhibitors with an affinity in the nanomolar range. Other proteins are currently being targeted.

(*)http://www.iecb.u-bordeaux.fr/teams/HUC/

 

    Collaborations:

     -  Dr I. Huc, CBMN & IECB, Bordeaux, (France).

     -  Dr C. Mackereth, ARNA INSERM U869, Bordeaux (France).

 

 

Proteins of therapeutic interest:

Mapacalcine: a way to new anti-ischemic protectors

Organ dysfunction due to ischemia, such as myocardial infarction, stroke or organ transplantation (ischemia-reperfusion), represents a major cause of treatment failure. A small protein, the mapacalcine, (MW 19 kDa) produced by the marine sponge Cliona vastifica is a specific blocker of calcium influxes particularly resistant to all known calcium channel blockers. Specific receptors for this protein have been detected in various tissues: intestinal smooth muscle, brain, kidney and liver. We demonstrated that the mapacalcine is able to protect hepatocytes and nervous cells against ischemia, thus increasing cell survival after an ischemic shock.

 

The main goals of the project are:

 - i)   to establish the structure – function relationships of mapacalcine to determine the minimum motif required for its activity,

 - ii) to improve the comprehension of the mechanisms triggering cell death after an ischemic shock,

 - iii)   to explore and apply the anti-ischemic properties of mapacalcine to pathologies linked to ischemia and particularly to organ preservation in graft protocols.

 

 

    Collaborations :

       -  Dr C. Heurteaux & M. Borsotto, IPMC, CNRS, UMR 7275, Valbonne (France) : Equipe Développement de stratégies thérapeutiques innovantes pour le traitement de la dépression et de l'AVC,

      -  Pr T. Hauet, IRTOMIT, INSERM U 1082 Poitiers (France): Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques.

      -  Pr X. Santarelli & Dr A. Noubhani, ENSTBB, Bordeaux (France).

 

GPC3: the end or the means against hepatocellular carcinoma:

Glypican 3 (GPC3) is a heparan-sulfate proteoglycan of which role in cell signalling remains to be unravelled. As a cell surface GPI-anchored glycoprotein and an extracellular co-receptor, it is involved in the control of growth factor/receptor interactions. GPC3 acts upstream of key signalling pathways (Wnt/β-catenin, Hh, BMP and FGF) involved in numerous cell functions.

Intriguingly GPC3 has opposite effects in several cancers. It acts as a tumour gene suppressor in lung and breast cancers, and as an oncogene in hepatocellular carcinoma and hepatoblastoma.

Our studies aim at getting more insights into GPC3 function at the molecular and cellular levels. Our strategy is based on the design and production of stable GPC3 mutants exhibiting well-defined activities on tumour cell growth. Solving the GPC3 3D structure is the starting point to identify small inhibitors by molecular docking. Identification of GPC3 partners allows getting more insights into the signalling pathways involved in tumorigenesis and possibly opens the way to new therapeutic strategies.

 

    Collaborations:

      - Dr C. Grosset, INSERM U1053, Bordeaux (France),

      - Pr X. Santarelli & Dr G. Joucla, ENSTBB, Bordeaux (France).

Team leader

SANTARELLI Xavier

Xavier SANTARELLI

Professor

CBMN @ ENSTBB

Ecole Nationale Supérieure de Technologie des Biomolécules (Bordeaux INP ENSTBB)

146 rue Léo Saignat 33000 Bordeaux

Tél : 05 57 57 10 44

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