Description du projet
Exploiter la lumière pour le contrôle cellulaire
L’optogénétique est une technologie révolutionnaire qui permet l’activation et le contrôle précis des fonctions biologiques des neurones ou d’autres types de cellules conçues pour réagir à la lumière. Cette méthode expérimentale introduit des protéines activées par la lumière dans les cellules et favorise une caractérisation et une manipulation précises des fonctions cellulaires. Cependant, la désactivation des cellules à l’aide d’intensités lumineuses modérées ou faibles reste un défi. Financé par le Conseil européen de la recherche, le projet MERA étudiera la rhodopsine-guanylyl-cyclase (RhGC), un nouveau photorécepteur sensoriel découvert dans le champignon Blastocladiella emersonii. Les chercheurs se sont fixé pour objectif de parfaitement comprendre le RhGC et d’en libérer tout le potentiel, ouvrant ainsi la voie à diverses applications dans le domaine de l’optogénétique et d’autres domaines de recherche.
Objectif
"Channelrhodopsin, which was discovered and described as a light-gated ion channel in my laboratory, has revolutionized the field of neuroscience over the past decade by enabling researchers to specifically activate selected neurons in a large ensemble of neuronal cells with short light flashes, a technology we now call ""Optogenetics."" However, though highly desirable, the inactivation of specific cells using moderate or low light intensities is not yet possible. The recently discovered rhodopsin-guanylyl-cyclase (RhGC) of the fungus Blastocladiella emersonii offers an elegant solution to this problem. Moreover, RhGC is a totally novel and uncharacterized sensory photoreceptor, and the first member of an enzyme rhodopsin family that urgently awaits in-depth characterization. Accordingly, the goal of the “mechanism of enzyme rhodopsin activation” (MERA) proposal is to obtain a comprehensive understanding of this novel photoreceptor, and to determine its functionality for broad application in optogenetics and other research fields. The MERA project is subdivided into four objectives. The first objective is the characterization and engineering of RhGC in cell lines and neurons as well as coexpression of RhGC with a cGMP-gated K+ channel to develop a ""Light-Hypopolarizer"" for cell inactivation. The second objective is to understand the dynamics of RhGC using a variety of biophysical technologies including time resolved UV-vis, FTIR, and Raman and EPR spectroscopy. A third objective is the generation of crystals for X-ray crystallography and the development of a three dimensional RhGC model. The fourth and final objective is the computer-aided conversion of RhGC into a rhodopsin-phosphodiesterase (RhPDE) for down-regulation of the second messenger cGMP and/or cAMP using light. The ultimate outcome will be a detailed understanding of a novel class of sensory photoreceptors with new perspectives for broad optogenetic applications."
Champ scientifique
- natural sciencesbiological sciencesneurobiology
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- natural sciencesbiological sciencesgeneticsnucleotides
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
- natural sciencesphysical sciencesopticsspectroscopy
Programme(s)
Thème(s)
Régime de financement
ERC-ADG - Advanced GrantInstitution d’accueil
10117 Berlin
Allemagne