Guillaume Sandoz - Profile on Academia.edu (original) (raw)
Papers by Guillaume Sandoz
Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat Migraine
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
Régulation des canaux calcium neuronaux sensibles au potentiel
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
Rhodopsins are ubiquitous light-driven membrane proteins with diverse functions, including ion tr... more Rhodopsins are ubiquitous light-driven membrane proteins with diverse functions, including ion transport. Widely distributed, they are also coded in the genomes of giant viruses infecting phytoplankton where their function is not settled. We examined the properties of three type 1 viral channelrhodopsins (VCR1s), and, unexpectedly, found that VCR1s accumulate exclusively intracellularly, and, upon illumination, induced calcium release from intracellular IP3dependent stores. In vivo, this light-induced calcium release was sufficient to remote control muscle contraction and behavior in VCR1-expressing tadpoles. VCR1s are the first rhodopsins shown to natively confer light-induced Ca 2+ release, suggesting an original mechanism for reshaping the response to light of virus-infected algae. The ability of VCR1s to photorelease calcium without altering plasma membrane electrical properties marks them as precursors for novel optogenetics tools, with potential applications in basic research and medicine.
Regulation of two-pore-domain potassium TREK channels and their involvement in pain perception and migraine
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.
Photopharmacological approaches for dissecting potassium channel physiology
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
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
A fine-tuned azobenzene for enhanced photopharmacology in vivo
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.
Mycolacton: ein Bakterientoxin als zukünftiges Schmerzmittel?
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.
Physical Review E, 2016
Microfluidic separation of magnetic particles is based on their capture by magnetized micro-colle... more Microfluidic separation of magnetic particles is based on their capture by magnetized micro-collectors while the suspending fluid flows past micro-collectors inside a micro-channel. Separation of nanoparticles is often challenging because of strong Brownian motion. Low capture efficiency of nanoparticles limits their applications in bio-analysis. However, at some conditions, magnetic nanoparticles may undergo field-induced aggregation that amplifies the magnetic attractive force proportionally to the aggregate volume and considerably increases nanoparticle capture efficiency. In this paper, we have demonstrated the role of such aggregation on an efficient capture of magnetic nanoparticles (about 80 nm in diameter) in a microfluidic channel equipped with a nickel micro-pillar array. This array was magnetized by an external uniform magnetic field, of intensity as low as 6-10 kA/m, and experiments were carried out at flow rates ranging between 0.3-30 µL/min. Nanoparticle capture is shown to be mostly governed by Mason number Ma, while the dipolar coupling parameter α does not exhibit a clear effect in the studied range, 1.4 < α < 4.5. The capture efficiency Λ shows a strongly decreasing Mason number behavior, Λ∝Ma -1.78 within the range, 32 ≤ Ma ≤ 3250. We have proposed a simple theoretical model, which considers destructible nanoparticles chains and gives the scaling behavior, Λ∝Ma -1.7 , close to the experimental findings.
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...
MECHANISMS OF SIGNAL TRANSDUCTION-The interaction between the I-II loop and the III-IV loop of Cav2. 1 contributes to voltage-dependent inactivation in a b-dependent manner
Régulation des canaux calcium neuronaux sensibles au potentiel
AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
Remotely control the activity of endogenous ion channels by light
Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat Migraine
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...
Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat Migraine
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
Régulation des canaux calcium neuronaux sensibles au potentiel
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
Rhodopsins are ubiquitous light-driven membrane proteins with diverse functions, including ion tr... more Rhodopsins are ubiquitous light-driven membrane proteins with diverse functions, including ion transport. Widely distributed, they are also coded in the genomes of giant viruses infecting phytoplankton where their function is not settled. We examined the properties of three type 1 viral channelrhodopsins (VCR1s), and, unexpectedly, found that VCR1s accumulate exclusively intracellularly, and, upon illumination, induced calcium release from intracellular IP3dependent stores. In vivo, this light-induced calcium release was sufficient to remote control muscle contraction and behavior in VCR1-expressing tadpoles. VCR1s are the first rhodopsins shown to natively confer light-induced Ca 2+ release, suggesting an original mechanism for reshaping the response to light of virus-infected algae. The ability of VCR1s to photorelease calcium without altering plasma membrane electrical properties marks them as precursors for novel optogenetics tools, with potential applications in basic research and medicine.
Regulation of two-pore-domain potassium TREK channels and their involvement in pain perception and migraine
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.
Photopharmacological approaches for dissecting potassium channel physiology
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
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
A fine-tuned azobenzene for enhanced photopharmacology in vivo
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.
Mycolacton: ein Bakterientoxin als zukünftiges Schmerzmittel?
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.
Physical Review E, 2016
Microfluidic separation of magnetic particles is based on their capture by magnetized micro-colle... more Microfluidic separation of magnetic particles is based on their capture by magnetized micro-collectors while the suspending fluid flows past micro-collectors inside a micro-channel. Separation of nanoparticles is often challenging because of strong Brownian motion. Low capture efficiency of nanoparticles limits their applications in bio-analysis. However, at some conditions, magnetic nanoparticles may undergo field-induced aggregation that amplifies the magnetic attractive force proportionally to the aggregate volume and considerably increases nanoparticle capture efficiency. In this paper, we have demonstrated the role of such aggregation on an efficient capture of magnetic nanoparticles (about 80 nm in diameter) in a microfluidic channel equipped with a nickel micro-pillar array. This array was magnetized by an external uniform magnetic field, of intensity as low as 6-10 kA/m, and experiments were carried out at flow rates ranging between 0.3-30 µL/min. Nanoparticle capture is shown to be mostly governed by Mason number Ma, while the dipolar coupling parameter α does not exhibit a clear effect in the studied range, 1.4 < α < 4.5. The capture efficiency Λ shows a strongly decreasing Mason number behavior, Λ∝Ma -1.78 within the range, 32 ≤ Ma ≤ 3250. We have proposed a simple theoretical model, which considers destructible nanoparticles chains and gives the scaling behavior, Λ∝Ma -1.7 , close to the experimental findings.
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...
MECHANISMS OF SIGNAL TRANSDUCTION-The interaction between the I-II loop and the III-IV loop of Cav2. 1 contributes to voltage-dependent inactivation in a b-dependent manner
Régulation des canaux calcium neuronaux sensibles au potentiel
AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
Remotely control the activity of endogenous ion channels by light
Two-Pore-Domain Potassium Channel Agonist to Efficiently Treat Migraine
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...