Share

Laetitia MONY

Researcher
Researcher
Manager of IBENS Xenopus facility
Biology
Neurobiology, Neuropharmacology, Photopharmacology, Biophysics, Structure-Activity relationships, Fluorescence, Ion channels
ENS-PSL
Department of Biology
Published on
11 October 2021
, updated on
22 February 2024
Laetitia Mony
Institut de biologie de l’ENS (IBENS)
46 rue d’Ulm 75005 Paris
Linkedin
Researchgate

Molecular neurobiologist, I work on the structure-function relationships of neuronal receptors. I develop innovative approaches combining pharmacology and light to control specific populations of receptors with strong selectivity.

Field of research

A current challenge lies in understanding the determinants of neurotransmitter receptor functional regulation and their physiological outcomes. Ionotropic glutamate receptors (iGluRs), a class of receptors involved in synaptic transmission and plasticity, are dynamic macromolecules endowed with multiple allosteric regulation sites. The structural changes allowing these sites to modulate channel gating and the receptor biological response are still ill-defined. I develop in the lab a fluorescence technique, voltage-clamp fluorometry, to study the role of the motion of specific receptor domains on iGluR regulation and signaling.

I furthermore develop approaches combining pharmacology and light (optopharmacology) targeting regulatory sites on NMDA receptors, a class of iGluRs, to specifically modulate subpopulations of this class of receptors in vivo. These approaches, based on original optochemical tools, aim at studying with an unprecedented precision the physiological role of NMDA receptor subpopulations, as well as determine the therapeutic relevance of targeting these subpopulations in neurological and psychiatric diseases linked to a dysfunction in neurotransmission.

Publications

Piot L., et al. GluD1 binds GABA and controls inhibitory plasticity. Science 382:1389-1394 (2023). https://doi.org/10.1126/science.adf3406

Geoffroy C., et al., Reversible inhibition of GluN2B-containing NMDA receptors with an in situ red-shifted, photoswitchable antagonist. BioRxiv 2023.10.16.562518 (2023). https://doi.org/10.1101/2023.10.16.562518

Mony L., and Paoletti, P. Mechanisms of NMDA receptor regulation. Curr Opin. Neurobiol. 83:102815 (2023). https://doi.org/10.1016/j.conb.2023.102815

Geoffroy C., Paoletti P., and Mony L. Positive allosteric modulation of NMDA receptors: mechanisms, physiological impact and therapeutic potential. J. Physiol. 600: 233–259 (2022). https://doi.org/10.1113/jp280875

Thapaliya E.R.*, Mony L.*, et al. Photochemical Control of Drug Efficacy: A Comparison of Uncaging and Photoswitching Ifenprodil on NMDA Receptors. ChemPhotoChem 5(5):445-454 (2021). * co-first authors. https://doi.org/10.1002/cptc.202000240

Mony L., et al. Dimer Interaction in Hv1 Proton Channel. Proc Natl. Acad. Sci. U.S.A 117(34):20898-20907 (2020). https://doi.org/10.1073/pnas.2010032117

Mony L.*, et al. A specialized molecular motion opens the Hv1 voltage-gated proton channel. Nat. Struct. Mol. Biol. 22(4): 283-90 (2015). https://doi.org/10.1038/nsmb.2978

Mony L., et al. Molecular Basis of Positive Allosteric Modulation of GluN2B NMDA receptors by polyamines. EMBO J. 30(15): 3134-46 (2011). https://doi.org/10.1038/emboj.2011.203     

Publications de Laetitia MONY