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SVNeuroTrans SIGNED

Mechanisms of neurotransmitter uptake and storage by synaptic vesicles

Total Cost €

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EC-Contrib. €

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Partnership

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 SVNeuroTrans project word cloud

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

exocytosis    unloading    inhibitory    viaat    printed    minute    svs    presynaptic    excitatory    inside    vitro    primary    either    solute    small    superfamily    draw    stored    contain    recombinant    tagged    leaking    assays    loaded    neurons    coupled    plan    atp    reporters    neurotransmitters    transmitter    sequester    transporter    pools    atpase    gradient    belong    proton    reconstituted    energy    unclear    ligands    liposomes    nerve    electrochemical    captured    concentrate    mm    sv    cultured    biochemical    exactly    transport    carrier    primarily    vesicular    loading    analyzing    ions    glass    vnut    glycine    endings    cells    summary    vgluts    kept    proteins    vgat    accommodated    created    glutamate    transmitters    fluorescent    prevented    employing    filled    despite    quantitative    linked    storage    probes    synaptic    combination    hundreds    surfaces    antibodies    membrane    gaba    isolation    transporters    purified    vesicles    isolated    labeled    microscopic    characterizing    released    microfluidic    artificial    vesicle    affinity    cytoplasmic    transfected    experiments    cns    progress    questions    largely    slc   

Project "SVNeuroTrans" 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: Munich
postcode: 80539
website: www.mpg.de

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]
 Total cost 2˙500˙000 €
 EC max contribution 2˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-10-01   to  2023-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (Munich) coordinator 2˙500˙000.00

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 Project objective

Summary In presynaptic nerve endings, neurotransmitters are stored in synaptic vesicles (SVs) before they are released by exocytosis. SVs contain specific transporters that sequester and concentrate transmitters from cytoplasmic pools. All known vesicular transporters belong to the solute carrier (SLC) superfamily of proteins. They draw the energy for transport from an electrochemical proton gradient created by a V-ATPase across the vesicle membrane. However, despite recent progress it is still largely unclear how synaptic vesicles are filled with hundreds of mM transmitter within less than a minute. Open questions include (1) how exactly transport is linked to the proton gradient and which ions are coupled to solute transport, (2) how two different transmitters can be accommodated by the same SV, and (3) how much transmitter can be loaded into an SV and how the stored transmitter is kept inside and prevented from leaking out. Here we will focus on the vesicular transporters for glutamate (VGLUTs) and GABA/glycine (VGAT or VIAAT), the main excitatory and inhibitory transmitters in the CNS, and on the vesicular transporter for ATP (VNUT). Primarily we will use biochemical approaches employing purified SVs and artificial vesicles, recombinant proteins (either purified and reconstituted in liposomes or using vesicles isolated from transfected cells), in combination with quantitative in vitro assays, for characterizing the features of transport and storage. To achieve this, we plan to develop advanced methods involving adaptation of new fluorescent probes and microscopic analysis of loading and unloading using microfluidic devices. For these experiments, vesicles will be captured by affinity ligands such as antibodies printed on glass surfaces. This allows for analyzing small numbers of vesicles such as SVs derived from primary cultured neurons or transport vesicles from transfected cells that are tagged and labeled with fluorescent reporters before isolation.

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