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Recherche
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
14 November 2021
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
Geoffroy C., Paoletti P., and Mony L. Positive allosteric modulation of NMDA receptors: mechanisms, physiological impact and therapeutic potential. J. Physiol. (2021). doi: 10.1113/JP280875.
Stroebel D., Mony L., and Paoletti P. Glycine agonism in ionotropic glutamate receptors. Neuropharmacology (2021). doi: 10.1016/j.neuropharm.2021.108631.
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)
Mony L., et al. Dimer Interaction in Hv1 Proton Channel. Proc Natl. Acad. Sci. U.S.A 117(34):20898-20907 (2020).
Klippenstein V.*, Mony L.*, and Paoletti P. Probing ion Channel Structure and Function Using Light-Sensitive Amino Acids. Trends. Biochem. 43(6):436-451 (2018).
Mony L.*, et al. A specialized molecular motion opens the Hv1 voltage-gated proton channel. Nat. Struct. Mol. Biol. 22(4): 283-90 (2015).
Mony L., et al. Molecular Basis of Positive Allosteric Modulation of GluN2B NMDA receptors by polyamines. EMBO J. 30(15): 3134-46 (2011).
Mony L., et al. Structural Basis of NR2B-Selective Antagonist Recognition by N-Methyl-D-Aspartate Receptors. Mol. Pharmacol. 75: 60-74 (2009).
Mony L., et al. Allosteric Modulators of NR2B-containing NMDA Receptors: Molecular Mechanisms and Therapeutic Potential. Br. J. Pharmacol. 157(8): 1301-1317 (2009).