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ConCorND SIGNED

Connectivity Correlate of Molecular Pathology in Neurodegeneration

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 ConCorND project word cloud

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

nd    ataxia    map    dependency    triggers    pathomechanisms    nds    exist    purkinje    signature    hypothesis    fibers    pharmacogenetics    cerebellar    elucidate    neuron    cfs    amplifying    proteomics    climbing    cell    degeneration    degenerative    structural    exists    socioeconomic    correlate    cascades    selective    incurable    neurons    dysfunctional    mouse    mechanisms    pc    signaling    presynaptic    mid    life    model    network    gap    alterations    diseases    altering    inputs    suboptimal    health    excitability    circuitry    spinocerebellar    pcs    transcriptomics    pathology    burden    progressive    connectome    conditional    neurodegenerative    onto    sca    first    maladaptive    pathogenic    compensatory    regulate    silencing    connectomics    synaptic    conceptual    models    earliest    alteration    trigger    spectrum    paralleling    molecular    modifications    therapies    revealed    cf    initiates    selectively    intrinsic    disease    dysfunction    neurodegeneration    deficits    govern    enormous    arise    enigmatic    circuit    excitatory    altered    debilitating    sca1    systematic    functioning    postsynaptic    delineate    entire    vulnerable   

Project "ConCorND" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAET BERN 

Organization address
address: HOCHSCHULSTRASSE 6
city: BERN
postcode: 3012
website: http://www.unibe.ch

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 Switzerland [CH]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-06-01   to  2022-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAET BERN CH (BERN) coordinator 2˙000˙000.00

Map

 Project objective

Neurodegenerative diseases (NDs) are incurable, debilitating conditions, arise mid-late in life, represent an enormous health and socioeconomic burden and no therapies exist. An enigmatic finding in NDs is the early and selective alteration in intrinsic excitability of vulnerable neurons paralleling changes in its circuitry. However, a gap in understanding exists in ND field about the cause of these alterations and whether these modifications regulate degenerative pathomechanisms. Our recent study, examining mechanisms of Purkinje cell (PC) degeneration in Spinocerebellar ataxia type 1 (SCA1) revealed that the earliest cerebellar alterations occur in the major excitatory inputs onto PCs, the climbing fibers (CFs). Based on this, we propose a novel three-step model of neurodegeneration: First, suboptimal functioning of the presynaptic inputs initiates signaling deficits in target PCs. Second, those alterations trigger maladaptive responses such as altered intrinsic PC excitability, thus amplifying pathogenic cascades. Third, at network level progressive dysfunction triggers compensatory synaptic modifications within the cerebellar circuitry. In this proposal, we will test our new hypothesis for NDs on SCA1 and this will be the first study to test circuit-dependency in NDs by selectively silencing presynaptic inputs and examining molecular responses in the postsynaptic neuron. Specifically, we will 1) Identify the dysfunctional CF associated molecular signature in PCs. 2) Elucidate mechanisms involved in altering intrinsic PC excitability. 3) Map the connectome for a structural correlate of the pathology. Using conditional mouse models, pharmacogenetics, transcriptomics, proteomics and connectomics, we will delineate molecular alterations that govern disease from compensatory alterations. Our systematic approach will not only impact SCA related therapies but the entire spectrum of NDs and has the potential to change the conceptual approach of future studies on NDs.

 Publications

year authors and title journal last update
List of publications.
2018 Federica Pilotto, Smita Saxena
Epidemiology of inherited cerebellar ataxias and challenges in clinical research
published pages: 2514183X1878525, ISSN: 2514-183X, DOI: 10.1177/2514183x18785258
Clinical and Translational Neuroscience 2/2 2019-04-25

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The information about "CONCORND" are provided by the European Opendata Portal: CORDIS opendata.

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