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LIIT-ChR2

Structural and mechanistic study of ion transport in Channelrhodopsin-2

Total Cost €

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EC-Contrib. €

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Partnership

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 LIIT-ChR2 project word cloud

Explore the words cloud of the LIIT-ChR2 project. It provides you a very rough idea of what is the project "LIIT-ChR2" about.

experimental    illumination    brain    neuronal    locations    rhodopsin    mixture    restore    microscopy    sampling    expressing    sensory    visual    biophysics    retinas    function    sensitivity    cycle    aring    activation    elucidating    transport    little    inactivation    chimera    structures    pass    action    matching    opening    projection    conformational    transient    proteins    chr2    enhanced    host    group    theoretical    absorbance    induces    found    bayesian    damaged    green    channels    map    ion    depolarized    bacteriorhodopsins    hoc    simulated    dark    retinal    reversibly    disorders    hence    channelrhodopsin    evidences    protein    free    ions    environment    structure    limited    mechanisms    halorhodopsins    algae    structural    ad    force    chr1    closed    observations    opens    mm    mechanics    closely    circuits    desensitized    close    channelrhodopsins    moiety    quantum    photoreceptors    light    electron    groups    ray    optogenetics    mechanism    species    qm    model    energy    validated    channel    neurons    turn    spectroscopic    cryo    molecular    contains    contrast    photochemical   

Project "LIIT-ChR2" data sheet

The following table provides information about the project.

Coordinator
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV 

Organization address
address: HOFGARTENSTRASSE 8
city: MUENCHEN
postcode: 80539
website: n.a.

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website http://www.biophys.mpg.de/en/tb/channelrhodopsin-2.html
 Total cost 159˙460 €
 EC max contribution 159˙460 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2015
 Duration (year-month-day) from 2015-04-01   to  2017-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (MUENCHEN) coordinator 159˙460.00

Map

 Project objective

Channelrhodopsins are type-I rhodopsin proteins found in green algae that function as sensory photoreceptors and turn into ion channels under illumination. Upon light absorbance, the retinal moiety induces a conformational change on the protein that opens a channel through which ions can pass. Neurons expressing channelrhodopsin-2 (ChR2) can be depolarized rapidly and reversibly by illumination, hence allowing control of the activation/inactivation of neurons in specific locations of the brain. For this reason, ChR2 has been used widely in optogenetics to study neuronal circuits and disorders in the brain, and to restore light sensitivity and visual capabilities in damaged retinas. However, in contrast to closely related bacteriorhodopsins or halorhodopsins, very little is known about their structure, light cycle and mechanism of action. The current structural evidences of ChR2 is limited to 1) the 6 Å projection map obtained by cryo-electron microscopy that contains a mixture of light (open channel) and dark (closed channel) states; and 2) the 2.3 Å X-ray structure of the dark state of a ChR1/ChR2 chimera. In the present proposal, we aim at elucidating the structure, properties and mechanism of action of the transient species of ChR2 during its photochemical cycle by means of theoretical methods and in close collaboration with the experimental biophysics groups of the host institute. The mechanisms of ion transport and channel opening will be simulated by enhanced sampling and free energy methods. Specific quantum-mechanics/molecular-mechanics (QM/MM) force matching force field will be generated ad hoc for the retinal moiety in the ChR2 environment. The model structures generated for the closed, open, and desensitized states will be validated 1) by comparison of the QM/MM spectroscopic properties of the model with experimental observations; and 2) by comparison to electron microscopy structures using a Bayesian analysis method recently developed in the host group.

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