Institut de Biologie StructuraleGrenoble / France

Contact person(s) related to this article / VIVAUDOU Michel

Michel Vivaudou Team

Current members

  • Michel Vivaudou, Research Director, CEA
  • Ana Sofia Eria Oliveira, PhD Student
  • Mathilde Folacci, PhD Student
  • Anaïs Bertaud, PhD Student (Codirected by Pierre Charnet, Univ Montpellier)

Research topics

Our laboratory is a member of the French National Laboratory of Excellence “Ion Channel Science and Therapeutics” supported by a network grant from ANR.

We study the molecular mechanisms of the function and the pharmacology of ion channels and other membrane proteins that may associate with them, such as ABC proteins and G-protein coupled receptors. Our work makes extensive use of ion-channel specific electrophysiological techniques (patch clamp, two-microelectrode voltage-clamp) as well as all manners of protein engineering techniques. The lab is equipped with manual setups for patch-clamp and TEVC, as well as robots for oocyte microinjection (RoboInject) and microelectrode recording (HiClamp). We also perform molecular dynamics simulation using 2 dedicated workstations and privileged access to CEA supercomputing center. We have a particular interest in the development of innovative techniques to study membrane proteins and analyze electrophysiological data.

Among our objects of interest are the inward-rectifying potassium channels Kir6.2 and Kir3.
Kir6.2 assembles with the ABC protein SUR to form the ATP-sensitive potassium channel (KATP). This channel, which has a key role in insulin secretion as well as in regulation of the activity of cardiac and neuronal cells, is a major pharmaceutical target. We study the physiological and pharmacological modulation of this channel, the impact of pathological mutations on its function, and the structures of its constituent subunits. We are also exploring ways to create light-modulated Kir6.2 which would be useful tools to explore their function in-vivo.
Kir3 proteins form the G-protein gated potassium channels GIRK, best known for their role in the vagal decrease in heart rate. We study its gating and regulation by GPCRs using molecular dynamics and electrophysiology. As with Kir6.2, we are designing light-modulated Kir3 channels as tools for optogenetics.
We also study the structure and function of microbial rhodopsins and ligand-gated channels in collaboration with groups working on their structures.

Current Collaborations

Valentin Gordeliy - IBS - Grenoble, France
Guillaume Sandoz - iBV - Nice, France
Bruno Allard - INMG - Lyon, France
Marc Delarue - Inst Pasteur - Paris, France
Pierre Charnet - IBMM - Montpellier, France

Current Funding

CEA, CNRS, ANR Network Grant LabEx ICST, ANR Project Grant Viral-Rhodopsins

Keywords

Ion channel - G-Protein Coupled Receptor - Potassium channel - Kir channel - K-ATP channel - Rhodopsin - Optogenetics

Specialized techniques

Protein engineering - Heterologous expression in Xenopus oocytes (manual and robotic setups) - Patch-clamp - Two-microelectrode voltage clamp (manual and robotic setups) - Surface expression measurements - Bioinformatics and molecular modelling

Recent publications

  • Le Tanno P, Folacci M, Revilloud J, Faivre L, Laurent G, Pinson L, Amedro P, Millat G, Janin A, Vivaudou M, Roux-Buisson N, Fauré J (2021) Characterization of Loss-Of-Function KCNJ2 Mutations in Atypical Andersen Tawil Syndrome. Front Genet 12:773177. doi : 10.3389/fgene.2021.773177
  • Goncalves J, Bartol TM, Camus C, Levet F, Menegolla AP, Sejnowski TJ, Sibarita JB, Vivaudou M, Choquet D, Hosy E (2020). Nanoscale co-organization and coactivation of AMPAR, NMDAR, and mGluR at excitatory synapses. Proc Natl Acad Sci U S A. 117 : 14503-11
  • Zabelskii D et al. (2020). Viral rhodopsins 1 are an unique family of light-gated cation channels. Nat Commun. 11 : 5707
  • Vivaudou M (2019). eeFit : a Microsoft Excel-embedded program for interactive analysis and fitting of experimental dose-response data. Biotechniques. 66 : 186-93
  • El-Khatib M, Nasrallah C, Lopes J, Tran QT, Tetreau G, Basbous H, Fenel D, Gallet B, Lethier M, Bolla JM, Pagès JM, Vivaudou M, Weik M, Winterhalter M, Colletier JP (2018). Porin self-association enables cell-to-cell contact in Providencia stuartii floating communities. Proc Natl Acad Sci U S A. 115 : E2220-8
  • Moreau CJ, Revilloud J, Caro LN, Dupuis JP, Trouchet A, Estrada-Mondragón A, Niescierowicz K, Sapay N, Crouzy S, Vivaudou M (2017). Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors. Sci Rep. 7 : 41154
  • Martel A, Antony L, Gerelli Y, Porcar L, Fluitt A, Hoffmann K, Kiesel I, Vivaudou M, Fragneto G, de Pablo JJ (2017). Membrane Permeation versus Amyloidogenicity : A Multitechnique Study of Islet Amyloid Polypeptide Interaction with Model Membranes. J Am Chem Soc. 139 : 137-48

Other selected publications

  • Vivaudou M, Todorov Z, Reyes-Mejia GC, Moreau C (2017). Ion Channels as Reporters of Membrane Receptor Function : Automated Analysis in Xenopus Oocytes. Methods Mol Biol. 1635 : 283-301
  • Moreau CJ, Niescierowicz K, Caro LN, Revilloud J, Vivaudou M (2015). Ion channel reporter for monitoring the activity of engineered GPCRs. Methods Enzymol. 556 : 425-54
  • Hosy E, Vivaudou M (2014). The unusual stoichiometry of ADP activation of the KATP channel. Front Physiol. 5 : 11. doi:10.3389/fphys.2014.00011
  • Niescierowicz K, Caro L, Cherezov V, Vivaudou M, Moreau CJ (2014). Functional assay for T4 lysozyme-engineered G protein-coupled receptors with an ion channel reporter. Structure. 22 : 149-55
  • Caro LN, Moreau CJ, Estrada-Mondragón A, Ernst OP, Vivaudou M (2012). Engineering of an artificial light-modulated potassium channel. PloS ONE. 7 : e43766
  • Bessadok A, Garcia E, Jacquet H, Martin S, Garrigues A, Loiseau N, André F, Orlowski S, Vivaudou M (2011). Recognition of sulfonylurea receptor (ABCC8/9) ligands by the multidrug resistance transporter P-glycoprotein (ABCB1) : functional similarities based on common structural features between two multispecific ABC proteins. J Biol Chem. 286 : 3552-69
  • Hosy E, Dupuis JP, Vivaudou M (2010). Impact of disease-causing SUR1 mutations on the KATP channel subunit interface probed with a rhodamine protection assay. J Biol Chem. 285 : 3084-91
  • Moreau CJ, Dupuis JP, Revilloud J, Arumugam K, Vivaudou M (2008). Coupling ion channels to receptors for biomolecule sensing. Nat Nanotechnol. 3 : 620-5
  • Moreau C, Jacquet H, Prost AL, D’hahan N, Vivaudou M (2000). The molecular basis of the specificity of action of KATP channel openers. EMBO J. 19 : 6644-51
  • D’hahan N, Moreau C, Prost AL, Jacquet H, Alekseev AE, Terzic A, Vivaudou M (1999). Pharmacological plasticity of cardiac ATP-sensitive potassium channels toward diazoxide revealed by ADP. Proc Natl Acad Sci U S A. 96 : 12162-7

Software

eeFit : an interactive program designed to fit Hill models to experimental dose-response data directly within Excel.
Download eeFit there

Contact

vivaudou[at]ibs[dot]fr