Christophe MOREAU

En résumé

Entreprises

• SGC, Medical Science Division, Université of Oxford, - Postdoctoral researcher Integral Membrane Proteins, Duerr's Group

  2016 - maintenant My roles in the Integral Membrane Protein group under the supervision of Dr. Katharina Dürr are:
  
  -Identification of interesting membrane proteins (receptors, channels, enzymes), which are putative drug targets among a list of more than 3000 putative described targets.
  
  -Design of protein constructs based of sequence comparisons, disorder and domains prediction.
  
  - Optimisation of the production of protein targets and detergent screening for extraction and monodispersity (We are usually working on 10-15 targets in parallel).
  
  - Optimisation of the membrane protein targets purification.
  
  - Crystallisation and solving structure of membrane proteins targets using X-Ray Crystallography and/or Cryo-EM.
  
  - Functional Characterization (ligand binding, protein-protein interaction).
  
  http://www.thesgc.org/scientists/groups/oxford
  

• Institut de Biologie Structurale - PhD Student

  2012 - 2015 PhD in Structural Biology (XRay Crystallography, Biochemistry, Immunology)
  
  Project: Investigation of molecular interaction between 3 parasites and the protein of the innate immune system.
  
  Achievements:
  
  -->Development of strategies to solve a complex biological system in 3 years with annual reports and oral communications.
  --> Daily scientific monitoring
  
  --> Analytical developments and process optimisation (protein purification, protein expression, protein crystallization, protein interaction, bacteria and mammalian cell cultures)
  
  --> 3 structures of pathogens' proteins (Xray crystallography, SAXS)
  --> Deciphering of interaction between parasite and human proteins (ELISA, SPR, NMR)
  --> Development of biotechnological tools (cloning and development of strategy to express a plasmatic protein in a recombinant system (mammalian tissues) / structural and functional characterization (SRP, ELISA, X-Ray Crystallography).
  
  Publications:
  
  

• Biochemistry Department, University of Cambridge, Leadlay's group - Postgraduate student

  2012 - 2012 Project: Deciphering the biosynthesis mechanisms of bacteria secondary metabolites, which are putative drugs: Polyketides.
  
  Achievements:
  ➢ Analytical development for identification of produced metabolites (HPLC, Mass spectrometry)
  ➢ Small molecules (fake-enzymatic ligands) purification and characterization (HPLC, MS-ESI Orbitrao, NMR 1D)
  ➢ Characterization of intermediate of enzymatic reaction (organic extraction, MS-ESI-Orbitrap)
  --> oral and written scientific report
  --> Daily scientific monitoring
  
  
  Details of the project:
  
  Polyketides represent a large family of secondary metabolites that demonstrate numerous pharmacological activities. They synthesized by plants, fungi and soil bacteria. Understanding their biosynthesis is an important challenge that provides the opportunity to discover new enzymatic activities. Early experiments showed that they are produced by the condensation of two carbon units, by a process similar to the production of fatty acids, and involves enormous multidomain enzymes or multiprotein complexes called polyketide synthases.
  Monensin A, which is produced by a Gram+ bacterium Streptomyces cinnamonensis, and is used as an antibiotic in veterinary medicine. It belong the polyether class of polyketides. The chemical reactions required for monensin A biosynthesis are known. However the timing of these events, in particular the epoxidation and cyclisation steps, remain obscure. To probe these steps, Professor Leadlay’s research group initiated a project that uses non-hydrolysable analogues of the malonyl extender units involved in polyketide biosynthesis. These are incorporated during chain elongation, and cause chain release. These intermediates can then be identified using high-resolution mass spectrometry. The use of deuterated and non-deuterated non-hydrolysable analogues provides robust evidence for any trapped intermediates.
  

• REMS Laboratory (RNP-RNA Structure and Function, Molecular and Structural Enzymology), Nancy - Postgraduate student

  2011 - 2011 Stage into Prof. G.Branlant and Prof. KJ Weissman group ( Molecular and Structural Enzymology group).
  
  Project: Investigation of red/ox enzymatic reactions
  
  Achievements
  
  ➢ Analytical development (FPLC)
  ➢ Molecular Biology (strategy cloning and plasmid production)
  ➢ Target proteins production and structural characterization (bacteria cells, chromatography, Circular Dichroïsm)
  ➢ Development of enzymatic reaction (UV spectroscopy, stopped-flow)
  ➢ Optimization purification and expression lab process (time, steps, quality)
  
  Project Details:
  
  H2O2 is an oxidizing agent that plays a part as a toxic molecule and also in cellular signaling, a process that is regulated by the overoxidation of the catalytic Cys of a class of eukaryotic peroxidases, the 2-Cys Peroxiredoxins, into sulfinic acid. The reduction of this form is catalyzed by Sulfiredoxin (Srx). The first step of the Srx reaction mechanism is the chemical activation of the sulfinic acid group by the transfer of the -phosphate of ATP. To determine whether the rate-limiting process of this step is associated with the chemical event of phosphate transfer, the rate of reaction has been compared in the presence of the co-substrates analogues of ATP and Mg2+, i.e, -thio-ATP and Mn2+. The results showed that 1) the rate-limiting step of the reaction is associated with the chemical process of phosphate transfer, and 2) the process depends on an ionizable group of pKapp 6,2 that corresponds to the -phosphate of ATP. One possible explanation to the low rate constant of this step could be a non-optimal positioning of the -phosphate of ATP relative to the sulfinic acid.
  
  ➢ Analytical development FPLC)
  ➢ Molecular Biology (strategy cloning and plasmid production)
  ➢ Target proteins production and structural characterization (bacteria cells, chromatography, Circular Dichroïsm)
  ➢ Development of enzymatic reaction (UV spectroscopy, stopped-flow)
  ➢ Optimize purification and expression lab process (time, steps, quality)
  

• REMS Laboratory (RNP-RNA Structure and Function, Molecular and Structural Enzymology), Nancy - Post graduate student

  2010 - 2010 Stage into Prof. G.Branlant and Prof. KJ Weissman group ( Molecular and Structural Enzymology group).
  
  Project: Investigation of the bacteria enzymatic reactions to resist to ampicillin antibiotic
  
  Achievements:
  
  -->Development/optimisation enzyme expression/purification (FPLC, cloning, bacteria expression).
  -->Optimisation of condition to determine enzymatic activities (creation of condition to mimic periplasm environment of bacteria enzymes).
  -->oral and written reports
  -->Daily scientific monitoring
  
  Project details:
  
  To synthesise the bacterial wall (peptidoglycan network), bacteria have to make link between peptides. These reaction are catalyzed by D-D transpeptidase. Because of we are able to block them with beta lactame antibiotic (as Ampicilin), bacteria developed alternative pathway which involves L-D transpeptidase (as YbiS).
  
  YbiS is making its job in an oxidative environment (the periplasm). That's why it could be inactivated by over oxidizing in sulfenic acid. My aim was to determine the kinetic constants in order to understand the mechanism of the recycling of YbiS protein from it inactive form (sulfenic acid) to it active form (thiolate) by two disulfide isomerases (which are involved in the isomerisation of bad di sulfide bonds) DsbC and DsbG.

• REMS Laboratory (RNP-RNA Structure and Function, Molecular and Structural Enzymology), Nancy - Graduate student

  2010 - 2010 Stage into Prof. C.Branlant group ( RNP-RNA Structure Functions).
  
  I studied snoRNP H/ACA box, these proteins are involved in the modification of ribosomal RNA. They are made up of one RNA and four proteins.
  
  My aim was to purify the complex of the 4 proteins which are belong to snoRNP H/ACA box of Archea.

Formations

• Université Grenoble 1 Joseph Fourier

  Grenoble 2012 - 2015 PhD/Doctorat
  
  Crystallography/Immunology
  
  Activities
  1-In charge of market research Innov'Doc (Junior company) (2013-2015)
  Innov'Doc is a Junior Company created from the formation of the University of Grenoble Research Industry and Innovation. We are offering our expertise to companies for assignments and consulting and we take part in informative congress in the Rhône-Alpes area. (www.innovdoc.fr) /
  2- Act

• Université Henri Poincaré UHP

  Vandoeuvre Les Nancy 2010 - 2012 Master degree's
  
  Biochemistry, Molecular Biology and Molecular Enzymology - mention très Bien (1st honours)
  
  

• Université Nancy 1 Henri Poincaré (Vandoeuvre Les Nancy)

  Vandoeuvre Les Nancy 2007 - 2010 Bachelor Degree's
  
  Biochemistry, Molecular Biology and Molecular Enzymology - mention Bien ( Second class honours, upper division)

Réseau

• Aude GERZAGUET

• Clément VUARCHEY

• Fanny RUCKSTUHL

• Gerard MARIE APOLLINE

• Jeanne LECLAIRE

• Jerome DUPUY

• Laure SELME-ROUSSEL

• Sophie FUCHS

• Youssef GHERMANI