Institut de Biologie de l'École Normale Supérieure ENS . CNRS UMR8197 . Inserm U1024 Directeur : Pierre Paoletti

December 2022

Thesis defense of Marco De Battista

Marco De Battista defended his thesis entitled "Molecular mechanisms of NMDA receptors containing GluN3A". Using a structure-function approach (site-directed mutagenesis, 2-electrode voltage clamp recordings in Xenopus oocytes and 3D modeling), Marco’s studies, carried out under the supervision of Pierre Paoletti and David Stroebel, revealed the importance of the LBD dimer interface in the control of the gating of GluN1/GluN3A excitatory glycine receptors, highlighting similarities and differences with other iGluRs.

July 2022

Thesis defense of Chloe Geoffroy

Chloe Geoffroy defended her thesis entitled "Optical control of GluN2B NMDA receptors". Chloé’s work, carried out under the supervision of Laetitia Mony and at the interface of chemistry and biology, has led to the development of new negative allosteric modulators specific to NMDA receptors that contain the GluN2B subunit and whose activity can be reversibly controlled by light. These new optopharmacology tools differ from classical pharmacology tools by their reversibility and fast dissociation kinetics and should help to better understand the role of GluN2B-type NMDA receptors in physiological or pathological processes of the central nervous system.

ANR 2022

Laetitia Mony, Inserm researcher, and David Stroebel, CNRS research engineer, have both obtained the 2022 ANR funding for their respective projects. This contract, for a maximum of 4 years, allow researchers to develop an original and high-level research programs.

The research project led by Laetitia Mony will study the diversity of NMDA receptors using optopharmacology.

The research project led by David Stroebel will explore the origin and evolution of signaling mediated by the iGluR family. This project will be carried out in collaboration with 3 other French research teams (IMBE Marseille, IRCAN Nice, Université de Nantes).

Ph.D fellowship

A Ph.D fellowship form the Fondation pour la Recherche Médicale (FRM) was attributed to Julia Doria (October 2022 - September 2025). Julia’s PhD project aims to study the mechanisms and signaling pathways of the non-canonical Delta-type ionotropic glutamate receptors.

May 2022

Laetitia Mony HDR

Laetitia Mony defended her HDR entitled: "Optical approaches to control and investigate glutamate receptors with specific stoichiometries" on May 16, 2022. Her project aims at developing innovative pharmacological optogenetic tools to study the molecular mechanisms and physiology of ionotropic glutamate receptors with unprecedented molecular and cellular specificity.

December 2021

Thesis defense of Laura Piot

Laura Piot defended her thesis entitled « New insights on the structure, function and pharmacology of Delta receptors ».
This work, done under the supervision of Pierre Paoletti and Laetitia Mony, and combining various experimental approaches (cellular electrophysiology, ’voltage-clamp fluorometry’ (VCF) but also X-ray crystallography and synaptic physiology), unveiled unsuspected properties of delta GluD1 receptors, a family of glutamate receptors abundantly expressed in the brain, but whose mechanisms and physiological roles remain poorly understood. The results obtained offer new perspectives on our understanding of glutamate receptors and the regulation of the synapse. They also highlight the power of the VCF technique for the study of glutamate receptor structure-function and pharmacology, thus opening new field of investigation on these essential actors of neurotransmission.

October 2020

Ph.D fellowship

A CDSN Ph.D fellowship (from ENS) was attributed to Antoine Sicard (October 2020 - September 2023). Antoine’s Ph.D project aims to develop innovative tools of genetic optopharmacology to study the functional diversity of NMDA receptors.

September 2019

Thesis defense of Benjamin Serraz

Benjamin Serraz defended his thesis entitled «Role of zinc in normal and pathological synaptic transmisson», done under the supervision of Pierre Paoletti and Mariano Casado.
By combining electrophysiological approaches on recombinant and native receptors, cell imaging and the use of new genetically modified mouse models, Benjamin showed that zinc is most likely a regulator at excitatory synapses on interneurons and that some subpopulations of these interneurons (SST+) are able to store vesicular zinc. He also showed that genetic mutations targeting the GluN2A subunit and that are linked to neurodevelopmental diseases in humans selectively impair NMDA receptor zinc sensitivity, pointing to zinc as an important regulator of brain function.

This work improves the understanding of an original neuromodulatory system that remains under investigated, and opens new conceptual and methodological perspectives regarding the role and distribution of free zinc in the brain.

January 2019

Pierre Paoletti, director of IBENS

Pierre Paoletti, head of the team "Glutamate Receptors and Excitatory Synapses", is appointed director of IBENS, starting January 1st, 2019.

October 2018

Ph.D fellowship

A Ph.D. fellowship from PSL Q-Life was attributed to Chloé Geoffroy (October 2018-September 2021). Chloé’s Ph.D project aims to develop new optopharmacological tools to selectively modulate GluN2B-containingg NMDA receptors in order to study their physiological and physiopathological roles.

July 2018

Thesis defense of Jean-Baptiste Esmenjaud

Jean-Baptiste Esmenjaud defended his thesis entitled «Structural dynamics and allostery of NMDA receptors». This work, done under the supervision of Pierre Paoletti and Antoine Taly (Institut de Biologie Physico-Chimique) and combining functional and computational analysis, proposes a comprehensive structural mechanism of long-distance allosteric transduction and domain coupling in intact NMDA receptors.

November 2017

Grand Prix Lamonica de Neurologie 2017

Pierre Paoletti is awarded the prestigious «Grand Prix Lamonica de Neurologie 2017- Académie des Sciences» for his work on glutamate receptors and on the control of excitatory synaptic transmission.

For more information, visit the Académie des Sciences website.

October 2017

ERC Advanced Grant 2015:

Pierre Paoletti, head of the team « Glutamate Receptors and Excitatory Synapses », was awarded the prestigious ERC Advanced Grant 2015 (European Research Council). Based on scientific excellence, ERC Grants encourage frontier research at the highest level. This five-year funding (2016-2021) will allow developing an original research program around « NMDA receptor diversity: from molecular dynamics to synaptic physiopathology».

For more information, visit the ERC website here.

Ph.D fellowship

A Ph.D fellowship from the Doctoral School ED158 Brain-Cognition-Behaviour (Université Pierre-et-Marie-Curie, UPMC) was attributed to Laura Piot (October 2017-September 2020). This fellowship will allow pursuing the promising research that Laura started during her Master 2 internship in our team. Laura’s Ph.D project aims to probe structural mechanisms responsible for the ionotropic and metabotropic signaling of NMDA receptors. To this end, she will use innovative opto-molecular approaches including incorporation of unnatural amino acids and voltage-clamp fluorometry.

September 2017

Pierre Paoletti, director of the ENS Department of Biology

Pierre Paoletti, head of the team "Glutamate Receptors and Excitatory Synapses", is appointed director of the ENS Department of Biology, starting September 1st, 2017.