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SynLink SIGNED

Molecular Structure and Engineering of Synaptic Organizer Proteins in Health and Disease

Total Cost €

0

EC-Contrib. €

0

Partnership

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 SynLink project word cloud

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

remodel    fundamental    specified    biophysical    network    synapses    cryo    cellular    models    ray    function    basic    soluble    cells    protein    dementia    membrane    exploited    techniques    microscopy    mechanistic    interactions    functionalize    yeast    reverse    basis    neurotransmission    question    electrophysiology    organize    insights    trans    animal    recruit    repair    disease    generating    hallmarks    structure    structures    mechanism    restoring    signalling    biology    structural    organizer    dependent    nanocolumn    culture    organizers    machinery    neurons    junctions    synapse    deterioration    engineering    imaging    synaptic    differentiation    mouse    pave    interaction    alzheimer    functions    defects    dysfunction    therapies    neurodegenerative    circuitry    adhesive    combine    electron    underlie    variants    simultaneously    neurotransmitter    cognition    leverage    modifying    persistent    neuronal    screening    lacking    communication    combinatorial    units    neuroscience    connectivity    principles    receptors    degeneration    molecular    variety    anchored    cognitive    display    surface    mediate    specialized    engineered    elucidate    form    ad    proteins    largely    recovery    reveal    crystallography   

Project "SynLink" data sheet

The following table provides information about the project.

Coordinator
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS 

Organization address
address: RUE MICHEL ANGE 3
city: PARIS
postcode: 75794
website: www.cnrs.fr

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 France [FR]
 Total cost 1˙499˙903 €
 EC max contribution 1˙499˙903 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-03-01   to  2025-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS FR (PARIS) coordinator 1˙499˙903.00

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 Project objective

Synapses are the specialized cellular junctions that form the basic units of communication between neuronal cells. Given the variety of network-dependent functions that synapses need to support, a fundamental question is how their properties are specified at the molecular level. Membrane-anchored and soluble “synaptic organizer proteins” form adhesive interactions that mediate synapse formation and differentiation. However, a structural and mechanistic understanding of how they recruit and organize the molecular machinery for neurotransmission is largely lacking. Simultaneously, dysfunction of synapses and loss of neurons are hallmarks of neurodegenerative disease that underlie a persistent deterioration of cognitive functions. The properties of synaptic organizer proteins to form and functionalize synapses could be exploited as a mechanism for synaptic repair to reverse neuronal degeneration.

The aims of this proposal are (i) to reveal the structural basis for trans-synaptic molecular nanocolumn formation by determining the complex structures of synaptic organizer proteins and neurotransmitter receptors, and (ii) to leverage insights into the structure and function of soluble synaptic organizers for generating engineered variants that can remodel synapses with the potential for restoring neuronal circuitry and cognition in animal models of Alzheimer’s disease (AD), the most common form of dementia associated with early defects in synaptic function.

To achieve these aims, I will combine techniques of structural biology (X-ray crystallography, cryo-electron microscopy and biophysical interaction analysis), protein engineering (combinatorial screening using yeast surface display), and cellular neuroscience (neuronal culture, electrophysiology, advanced imaging and mouse models). Our results will elucidate fundamental principles of synaptic signalling and pave the way for disease-modifying therapies that focus on recovery of synaptic connectivity and function.

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

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