Guillaume Sandoz - Academia.edu (original) (raw)
Uploads
Papers by Guillaume Sandoz
Dataset for the pubilcation "Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat ... more Dataset for the pubilcation "Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat Migraine" the excel files contains all the data obtained for the 4 figures of the publications: -the bahavior in mice -the electrophysiology of primary neuronal culture -Behavior in rats
AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
Proceedings of the National Academy of Sciences of the United States of America, Mar 28, 2016
bioRxiv (Cold Spring Harbor Laboratory), May 25, 2023
Neuroscience Letters, Mar 1, 2022
The ability to sense pain signals is closely linked to the activity of ion channels expressed in ... more The ability to sense pain signals is closely linked to the activity of ion channels expressed in nociceptors, the first neurons that transduce noxious stimuli into pain. Among these ion channel, TREK1, TREK2 and TRAAK from the TREK subfamily of the Two-Pore-Domain potassium (K2P) channels, are hyperpolarizing channels that render neurons hypoexcitable. They are regulated by diverse physical and chemical stimuli as well as neurotransmitters through G-protein coupled receptors activation. Here, we review the molecular mechanisms underlying these regulations and their functional relevance in pain and migraine induction.
Current Opinion in Pharmacology, Apr 1, 2022
Photopharmacology allows for the remote control of ion channels and receptors by the application ... more Photopharmacology allows for the remote control of ion channels and receptors by the application of light-sensitive compounds. Upon irradiation with light these molecules change their configuration, enabling channel modulation with both spatial and temporal resolution. For the control of potassium channel physiology mainly two approaches have evolved. Photoswitchable tethered ligands (PTLs) and freely diffusible photochromic ligands (PCLs), targeting K+ channels, serve to gain insights in neuronal functions of the brain and the heart, whereby the molecules have been refined in the past years with special focus on improving switching characteristics in terms of red-shifted wavelengths and temporal resolution. In this review we provide an overview about the application of these tools in studying potassium channels and neuronal circuit, highlighting recent developments towards future implementations.
M S-medecine Sciences, Nov 1, 2012
The Neuroscientist, Jul 27, 2020
Cell Chemical Biology, 2021
Despite the power of photopharmacology for interrogating signaling proteins, many photopharmacolo... more Despite the power of photopharmacology for interrogating signaling proteins, many photopharmacological systems are limited by their efficiency, speed, or spectral properties. Here, we screen a library of azobenzene photoswitches and identify a urea-substituted "azobenzene-400" core that offers bistable switching between cis and trans with improved kinetics, light sensitivity, and a red-shift. We then focus on the metabotropic glutamate receptors (mGluRs), neuromodulatory receptors that are major pharmacological targets. Synthesis of "BGAG12,400," a photoswitchable orthogonal, remotely tethered ligand (PORTL), enables highly efficient, rapid optical agonism following conjugation to SNAP-tagged mGluR2 and permits robust optical control of mGluR1 and mGluR5 signaling. We then produce fluorophore-conjugated branched PORTLs to enable dual imaging and manipulation of mGluRs and highlight their power in ex vivo slice and in vivo behavioral experiments in the mouse prefrontal cortex. Finally, we demonstrate the generalizability of our strategy by developing an improved soluble, photoswitchable pore blocker for potassium channels.
Journal Club Schmerzmedizin, 2014
Buruli Ulcer ist eine durch das Bakterium Mycobakterium ulcerans hervorgerufene Krankheit der Hau... more Buruli Ulcer ist eine durch das Bakterium Mycobakterium ulcerans hervorgerufene Krankheit der Haut und Weichteile. Durch das Toxin Mycolacton entstehen dabei grose Gewebeschaden, die zu Beginn der Krankheit keine Schmerzen hervorrufen. Betroffene nehmen daher die Gewebelasionen erst ernst, wenn die Krankheit schon weit fortgeschritten ist. Wissenschaftler um Priscilla Brodin und Laurent Marsollier vom franzosischen Zentrum fur wissenschaftliche Forschung (CNRS) haben nun den molekularen Mechanismus dieser Analgesie aufgedeckt.
eLife, 2016
During cortical development, the identity of major classes of long-distance projection neurons is... more During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mecha...
AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
Dataset for the pubilcation "Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat ... more Dataset for the pubilcation "Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat Migraine" the excel files contains all the data obtained for the 4 figures of the publications: -the bahavior in mice -the electrophysiology of primary neuronal culture -Behavior in rats
Nature Communications, 2011
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and ga... more Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and gates non-selective cation channels. The origins of glutamate receptors are not well understood as they differ structurally and functionally from simple bacterial ligand-gated ion channels. Here we report the discovery of an ionotropic glutamate receptor that combines the typical eukaryotic domain architecture with the 'TXVGYG' signature sequence of the selectivity filter found in K + channels. This receptor exhibits functional properties intermediate between bacterial and eukaryotic glutamate-gated ion channels, suggesting a link in the evolution of ionotropic glutamate receptors.
Proceedings of the National Academy of Sciences, 2011
TREK channels produce background currents that regulate cell excitability. These channels are sen... more TREK channels produce background currents that regulate cell excitability. These channels are sensitive to a wide variety of stimuli including polyunsaturated fatty acids (PUFAs), phospholipids, mechanical stretch, and intracellular acidification. They are inhibited by neurotransmitters, hormones, and pharmacological agents such as the antidepressant fluoxetine. TREK1 knockout mice have impaired PUFA-mediated neuroprotection to ischemia, reduced sensitivity to volatile anesthetics, altered perception of pain, and a depression-resistant phenotype. Here, we investigate TREK1 regulation by Gq-coupled receptors (GqPCR) and phospholipids. Several reports indicate that the C-terminal domain of TREK1 is a key regulatory domain. We developed a fluorescent-based technique that monitors the plasma membrane association of the C terminus of TREK1 in real time. Our fluorescence and functional experiments link the modulation of TREK1 channel function by internal pH, phospholipid, and GqPCRs to TR...
Dataset for the pubilcation "Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat ... more Dataset for the pubilcation "Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat Migraine" the excel files contains all the data obtained for the 4 figures of the publications: -the bahavior in mice -the electrophysiology of primary neuronal culture -Behavior in rats
AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
Proceedings of the National Academy of Sciences of the United States of America, Mar 28, 2016
bioRxiv (Cold Spring Harbor Laboratory), May 25, 2023
Neuroscience Letters, Mar 1, 2022
The ability to sense pain signals is closely linked to the activity of ion channels expressed in ... more The ability to sense pain signals is closely linked to the activity of ion channels expressed in nociceptors, the first neurons that transduce noxious stimuli into pain. Among these ion channel, TREK1, TREK2 and TRAAK from the TREK subfamily of the Two-Pore-Domain potassium (K2P) channels, are hyperpolarizing channels that render neurons hypoexcitable. They are regulated by diverse physical and chemical stimuli as well as neurotransmitters through G-protein coupled receptors activation. Here, we review the molecular mechanisms underlying these regulations and their functional relevance in pain and migraine induction.
Current Opinion in Pharmacology, Apr 1, 2022
Photopharmacology allows for the remote control of ion channels and receptors by the application ... more Photopharmacology allows for the remote control of ion channels and receptors by the application of light-sensitive compounds. Upon irradiation with light these molecules change their configuration, enabling channel modulation with both spatial and temporal resolution. For the control of potassium channel physiology mainly two approaches have evolved. Photoswitchable tethered ligands (PTLs) and freely diffusible photochromic ligands (PCLs), targeting K+ channels, serve to gain insights in neuronal functions of the brain and the heart, whereby the molecules have been refined in the past years with special focus on improving switching characteristics in terms of red-shifted wavelengths and temporal resolution. In this review we provide an overview about the application of these tools in studying potassium channels and neuronal circuit, highlighting recent developments towards future implementations.
M S-medecine Sciences, Nov 1, 2012
The Neuroscientist, Jul 27, 2020
Cell Chemical Biology, 2021
Despite the power of photopharmacology for interrogating signaling proteins, many photopharmacolo... more Despite the power of photopharmacology for interrogating signaling proteins, many photopharmacological systems are limited by their efficiency, speed, or spectral properties. Here, we screen a library of azobenzene photoswitches and identify a urea-substituted "azobenzene-400" core that offers bistable switching between cis and trans with improved kinetics, light sensitivity, and a red-shift. We then focus on the metabotropic glutamate receptors (mGluRs), neuromodulatory receptors that are major pharmacological targets. Synthesis of "BGAG12,400," a photoswitchable orthogonal, remotely tethered ligand (PORTL), enables highly efficient, rapid optical agonism following conjugation to SNAP-tagged mGluR2 and permits robust optical control of mGluR1 and mGluR5 signaling. We then produce fluorophore-conjugated branched PORTLs to enable dual imaging and manipulation of mGluRs and highlight their power in ex vivo slice and in vivo behavioral experiments in the mouse prefrontal cortex. Finally, we demonstrate the generalizability of our strategy by developing an improved soluble, photoswitchable pore blocker for potassium channels.
Journal Club Schmerzmedizin, 2014
Buruli Ulcer ist eine durch das Bakterium Mycobakterium ulcerans hervorgerufene Krankheit der Hau... more Buruli Ulcer ist eine durch das Bakterium Mycobakterium ulcerans hervorgerufene Krankheit der Haut und Weichteile. Durch das Toxin Mycolacton entstehen dabei grose Gewebeschaden, die zu Beginn der Krankheit keine Schmerzen hervorrufen. Betroffene nehmen daher die Gewebelasionen erst ernst, wenn die Krankheit schon weit fortgeschritten ist. Wissenschaftler um Priscilla Brodin und Laurent Marsollier vom franzosischen Zentrum fur wissenschaftliche Forschung (CNRS) haben nun den molekularen Mechanismus dieser Analgesie aufgedeckt.
eLife, 2016
During cortical development, the identity of major classes of long-distance projection neurons is... more During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mecha...
AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
Dataset for the pubilcation "Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat ... more Dataset for the pubilcation "Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat Migraine" the excel files contains all the data obtained for the 4 figures of the publications: -the bahavior in mice -the electrophysiology of primary neuronal culture -Behavior in rats
Nature Communications, 2011
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and ga... more Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and gates non-selective cation channels. The origins of glutamate receptors are not well understood as they differ structurally and functionally from simple bacterial ligand-gated ion channels. Here we report the discovery of an ionotropic glutamate receptor that combines the typical eukaryotic domain architecture with the 'TXVGYG' signature sequence of the selectivity filter found in K + channels. This receptor exhibits functional properties intermediate between bacterial and eukaryotic glutamate-gated ion channels, suggesting a link in the evolution of ionotropic glutamate receptors.
Proceedings of the National Academy of Sciences, 2011
TREK channels produce background currents that regulate cell excitability. These channels are sen... more TREK channels produce background currents that regulate cell excitability. These channels are sensitive to a wide variety of stimuli including polyunsaturated fatty acids (PUFAs), phospholipids, mechanical stretch, and intracellular acidification. They are inhibited by neurotransmitters, hormones, and pharmacological agents such as the antidepressant fluoxetine. TREK1 knockout mice have impaired PUFA-mediated neuroprotection to ischemia, reduced sensitivity to volatile anesthetics, altered perception of pain, and a depression-resistant phenotype. Here, we investigate TREK1 regulation by Gq-coupled receptors (GqPCR) and phospholipids. Several reports indicate that the C-terminal domain of TREK1 is a key regulatory domain. We developed a fluorescent-based technique that monitors the plasma membrane association of the C terminus of TREK1 in real time. Our fluorescence and functional experiments link the modulation of TREK1 channel function by internal pH, phospholipid, and GqPCRs to TR...