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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.

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

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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