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Tau Seeding SIGNED

Identification and validation of human proteins that control tau seeding in cell-based and in vivo models

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 Tau Seeding project word cloud

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

cell    microtubule    function    therapeutic    propagation    purpose    biosensor    mechanism    proteins    screens    cycle    stall    drug    screen    modulation    elegans    influence    premise    chemical    translationally    regulators    tauopathies    preselected    cascade    models    modify    lay    sensitive    illnesses    foundation    delineate    compounds    attempted    comprehensively    seeding    robustly    kinases    soluble    unravel    genes    cellular    ultimately    neurodegenerative    share    interfere    neurological    misfolding    disease    medium    molecular    indirectly    shrna    life    post    perform    seeds    mechanistic    relationships    aggregates    500    slow    validation    gene    tau    understand    linked    disorders    self    causal    strategies    progression    interactors    knockdown    hypothesized    inhibit    literature    alzheimer    hits    details    network    modulate    systematic    functional    pathogenic    templates    misfolded    assay    proteostasis    fret    protein   

Project "Tau Seeding" data sheet

The following table provides information about the project.

Coordinator
MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) 

Organization address
address: ROBERT ROSSLE STRASSE 10
city: BERLIN
postcode: 13125
website: www.mdc-berlin.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 171˙460 €
 EC max contribution 171˙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-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-11-01   to  2020-11-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) DE (BERLIN) coordinator 171˙460.00

Map

 Project objective

The microtubule-associated protein tau is the most commonly misfolded protein in neurodegenerative disorders including Alzheimer’s disease and other related tauopathies. These neurological illnesses are hypothesized to share a common mechanism of disease progression, where pathogenic aggregates or ‘seeds’ of the tau protein function as templates promoting misfolding of functional, soluble tau protein. Under this premise, therapeutic strategies that modulate the seeding cascade, have high potential to interfere with the disease process. I will apply a recently developed highly sensitive and specific FRET-based biosensor cell assay as well as C.elegans to identify proteins that robustly influence tau seeding to understand the self-propagation process, ultimately aiming to stall disease progression. To this purpose, I will perform an shRNA-based knockdown screen of ~500 target genes preselected from literature, with potential to influence tau seeding. These will include known interactors of tau, proteostasis and tau life cycle regulators, and kinases, which modify tau post-translationally. After systematic validation, hits will be comprehensively investigated to unravel the mechanistic details of how modulation of the seeding activity was induced by the relevant gene. In addition, based on the results from the cellular assay, network models will be generated that delineate the causal relationships between identified target genes and tau seeding. This will help to understand, which proteins are able to directly or indirectly affect tau seeding, based on which new drug screens can be established. Moreover, already known drug targets will be attempted to be linked to cellular pathways, which have been identified to be relevant to tau seeding. In the medium term, this study may not only identify novel target genes and molecular pathways but also lay the important foundation to identify chemical compounds that slow or inhibit tau seeding.

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

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