Objectif Acetylcholine receptor is an essential component of central and peripheral nervous systems which plays a key role in numerous physiological and pathological processes. In particular, acetylcholine receptor is responsible for the coupling between nervous and muscular system at the neuromuscular junction as they are activated following acetylcholine release from neurons to triggers muscle contraction. Despite extensive work to decipher the molecular properties of the receptor itself, how the activity of the receptor and the signal following its activation are modulated is still poorly understood. This is yet an important question to address as impairment in acetylcholine receptor-associated signalling is involved in neuromuscular pathologies such as myasthenia gravis or congenital myasthenic syndrome. Here, we propose to use the genetic animal model Caenorhabditis elegans to study the dynamic regulation of acetylcholine receptors. This nematode is a powerful tool to study acetylcholine receptor as this animal also uses acetylcholine as an excitatory neurotransmitter at the neuromuscular junction. In nematode, acetylcholine receptors are sensitive to levamisole, a specific agonist. Prolonged exposure to levamisole leads to hypercontraction of the worms and finally to their paralysis. However, mutations in genes associated to acetylcholine receptor activity or biosynthesis enable the worms to adapt to levamisole. In this project, using proteomic and genetic approaches based on levamisole adaptation, we will identify several new regulators of acetylcholine receptor and of the associated signalling pathway. Deeper functional characterization will be performed on the new regulators evolutionary conserved that then may be involved in some neuromuscular pathologies. This research will give new insights into functional dynamic of acetylcholine receptor and may then shed a new light on the cause of impaired functioning of acetylcholine receptor in diseases. Champ scientifique medical and health sciencesbasic medicineneurologydementiaalzheimernatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicineneurologyparkinsonmedical and health sciencesbasic medicinephysiologyhomeostasis Mots‑clés Acetylcholine receptor neuromuscular junction C. elegans levamisole Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2017 - Individual Fellowships Appel à propositions H2020-MSCA-IF-2017 Voir d’autres projets de cet appel Régime de financement MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinateur UNIVERSITE LYON 1 CLAUDE BERNARD Contribution nette de l'UE € 185 076,00 Adresse BOULEVARD DU 11 NOVEMBRE 1918 NUM43 69622 Villeurbanne Cedex France Voir sur la carte Région Auvergne-Rhône-Alpes Rhône-Alpes Rhône Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 185 076,00