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Mechanism of Enzyme Rhodopsin Activation

Descripción del proyecto

Aprovechar la luz para el control celular

La optogenética es una tecnología revolucionaria que permite activar y controlar con precisión las funciones biológicas de las neuronas u otros tipos de células diseñadas para responder a la luz. Este método experimental introduce en las células proteínas fotoactivadas y facilita la caracterización y manipulación precisas de las funciones celulares. Sin embargo, la capacidad de desactivar las células utilizando intensidades de luz moderadas o bajas sigue siendo un reto. El equipo del proyecto MERA, financiado por el Consejo Europeo de Investigación, analizará rodopsina-guanilato-ciclasa (RhGC), un nuevo fotorreceptor sensorial hallado en el hongo «Blastocladiella emersonii». El objetivo de los investigadores es comprender a fondo RhGC y liberar todo su potencial, lo que allanará el camino para diversas aplicaciones en optogenética y otros campos de investigación.

Objetivo

"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."

Régimen de financiación

ERC-ADG - Advanced Grant

Institución de acogida

HUMBOLDT-UNIVERSITAET ZU BERLIN
Aportación neta de la UEn
€ 2 398 750,00
Dirección
UNTER DEN LINDEN 6
10117 Berlin
Alemania

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Región
Berlin Berlin Berlin
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 2 398 750,00

Beneficiarios (1)