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Institut de Biologie StructuraleGrenoble / France

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

Presentation of the Channels Group

Group leader: Michel Vivaudou

Team

  • Christophe Moreau, researcher CR1 CNRS
  • Jean Revilloud, assistant-engineer CNRS
  • Lavinia Liguori, Postdoctoral fellow
  • Gina Catalina Reyes-Mejia, PhD Student
  • Zlatomir Todorov, PhD Student
  • Laura Lemel, PhD Student
  • Mimoun Jaouan, Master 2 student

Alummi

  • Maria-Antonietta Principalli, PhD Student
  • Ana Sofia Oliveira, summer intern (Univ Lisbon)
  • Karla Langer, Postdoctoral fellow
  • Harita Yedavally, Master student
  • Géraldine Goubet, Technician trainee
  • Katharina Haspel, Erasmus student (Now in York, UK)
  • Charlotte Haas, Technician trainee
  • Anaelle Rongier, Master student (Now in Grenoble)
  • Katarzyna Niescierowicz, PhD Student (Now in Poland)
  • Stéphanie Simonet, Master student (Now in Lyon)
  • Ali Sassi, Postdoctoral fellow (Now in Paris)
  • Argel Estrada-Mondragón, Postdoctoral fellow (Now in Brisbane)
  • Anne Martel, Postdoctoral fellow (Now at ILL, Grenoble)
  • Nicolas Merk, Master student (from Univ Copenhaguen)
  • Lydia Caro, PhD student (Now in Toronto)
  • Iulia Blesneac, PhD student (Now in Montpellier)
  • Laurie-Anne Payet, Master 2 student (Now in Switzerland)
  • Guillaume Tourcier, Technician trainee (Now at IBS, Grenoble)
  • Julien Dupuis, PhD student (Now in Bordeaux)
  • Eric Hosy, Postdoctoral fellow (Now in Bordeaux)

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 a dedicated workstation and privileged access to CEA supercomputing center. We have a particular interest in the development of innovative techniques to study membrane proteins.

Our favorite model has long been the ATP-sensitive potassium channel (KATP) that is formed by assembly of a K+ channel (Kir6.2) and an ABC protein (SUR). 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.
Another focus is Ion Channel-Coupled Receptors (ICCR). ICCRs are fusion of a G Protein-Coupled Receptors (GPCR) with the Kir6.2 channel, engineered so that ligand binding to the receptor translates into a gating change in the channel, easily detectable by electrophysiological techniques. ICCRs are used to study the pharmacology, dynamics and structure of GPCR and to construct biosensors for application in basic and applied research.
We also work on G-protein gated channels GIRK (or Kir3) and their regulation by GPCRs.

Keywords

Ion channel - G-Protein Coupled Receptor - Potassium channel - Kir channel - K-ATP channel - ABC transporter - SUR - MRP1 - P-glycoprotein - biosensor

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) - Measurement of surface expression of membrane proteins (chemiluminescence, confocal microscopy) - Membrane protein expression (cell-free, bacteria, insect cells, yeasts) and purification - Bioinformatics and molecular modelling

Selected publications

  • Hassaine G, Deluz C, Grasso L, Wyss R, Tol MB, Hovius R, Graff A, Stahlberg H, Tomizaki T, Desmyter A, Moreau C, Li XD, Poitevin F, Vogel H, Nury H (2014). X-ray structure of the mouse serotonin 5-HT3 receptor. Nature. 512: 276-81
  • 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
  • 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
  • Sapay N, Estrada-Mondragon A, Moreau C, Vivaudou M, Crouzy S (2014). Rebuilding a macromolecular membrane complex at the atomic scale: Case of the Kir6.2 potassium channel coupled to the muscarinic acetylcholine receptor M2. Proteins. 82: 1694-707
  • Caro LN, Moreau CJ, Estrada-Mondragón A, Ernst OP, Vivaudou M (2012). Engineering of an artificial light-modulated potassium channel. PloS ONE. 7: e43766
  • Moreau CJ, Dupuis JP, Revilloud J, Arumugam K, Vivaudou M (2008). Coupling ion channels to receptors for biomolecule sensing. Nature Nanotech. 3: 620-5

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