Institut de Biologie StructuraleGrenoble / France

Contacts relatifs à cet article / VIVAUDOU Michel

Michel Vivaudou Team

Team leader : Michel Vivaudou

Team

  • Jean Revilloud, assistant-engineer CNRS
  • Zlatomir Todorov, PhD Student
  • Ana Sofia Oliveira, PhD Student
  • Mathilde Folacci, PhD Student

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.

Our two main 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.

Keywords

Ion channel - G-Protein Coupled Receptor - Potassium channel - Kir channel - K-ATP channel - ABC transporter - SUR - optogenetics

Specialized techniques

Construction of mutants, chimeras, fusion proteins - Heterologous expression in Xenopus oocytes (manual and robotic setups) - Patch-clamp on cells and proteoliposomes - Two-microelectrode voltage clamp (manual and robotic setups) - Bioinformatics and molecular modelling

Selected publications

  • Vivaudou M (2019). eeFit : A Microsoft Excel-embedded program for interactive analysis and fitting of experimental dose-response data. Biotechniques (in press)
  • 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
  • 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

The list of all the publications of the group is available here.