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PDPcardio SIGNED

Protein phosphatase 1-disrupting peptides: Scope and mechanism of action in the treatment of heart insufficiency

Total Cost €

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EC-Contrib. €

0

Partnership

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 PDPcardio project word cloud

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

sr    nevertheless    generally    combined    principles    subunit    data    mediated    signaling    dephosphorylation    action    heart    pathologies    guide    bound    protein    applicable    beneficial    sarcoplasmic    indicated    dysfunctions    tissue    amount    hyperactivity    counteracts    strategies    scope    seals    threonines    release    unknown    kinase    hard    serines    roles    holoenzymes    enzyme    deregulation    cardiac    regulatory    expressed    interaction    calcium    disrupting    proteomics    phosphorylated    physiological    pdp    proteins    fundamental    insufficiency    pp1c    fine    basis    lies    regulation    tune    biology    peptides    substrates    synthetic    mechanisms    catalytic    cells    tools    pdpcardio    powerful    dephosphorylate    unclear    drugs    underlying    ubiquitously    showed    reticulum    receptor    potentially    phosphatase    selectively    tool    implicated    ryr2    interactions    chemical    arrhythmogenic    pp1    ligands    accordingly    cardiomyocytes    play    effect    ryanodine    pdps    homoeostasis    leak    human    treatment    mechanistic    therapeutic   

Project "PDPcardio" data sheet

The following table provides information about the project.

Coordinator
ALBERT-LUDWIGS-UNIVERSITAET FREIBURG 

Organization address
address: FAHNENBERGPLATZ
city: FREIBURG
postcode: 79098
website: www.uni-freiburg.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 1˙998˙750 €
 EC max contribution 1˙998˙750 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-COG
 Funding Scheme ERC-COG
 Starting year 2020
 Duration (year-month-day) from 2020-02-01   to  2025-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ALBERT-LUDWIGS-UNIVERSITAET FREIBURG DE (FREIBURG) coordinator 1˙998˙750.00

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 Project objective

Protein phosphatase-1 (PP1) is a ubiquitously expressed enzyme known to dephosphorylate a large number of the phosphorylated serines and threonines. The catalytic subunit PP1c is bound to regulatory proteins in holoenzymes. These play specific and fundamental roles in physiological processes and pathologies. One key role lies in the regulation of important cardiac signaling pathways and calcium homoeostasis. Accordingly, deregulation of PP1 has been implicated in cardiac dysfunctions. Powerful tools to study PP1 biology are our own developed PP1-disrupting peptides (PDPs) that selectively release PP1c (bound to PDP: PDP–PP1c) activity in cells. Recently, we showed that PDP treatment counteracts kinase hyperactivity and seals the arrhythmogenic sarcoplasmic reticulum (SR)-calcium-leak in human heart failure tissue. Mechanistic data indicated that PDP–PP1c-mediated dephosphorylation of the ryanodine receptor type 2 (RyR2) is involved in this effect. Nevertheless, given the large amount of potential PP1 substrates, so far the scope of PDP action is unknown, and therefore the mechanisms underlying this beneficial and potentially therapeutic effect of the PDPs in heart failure are unclear and currently hard to investigate. PDPcardio will address these challenges by providing new chemical biology methodologies combined with proteomics approaches using PDPs to guide PP1c to its substrates and to identify PDP-mediated interactions of PP1. These strategies will enable identifying the scope of PDP action in general, and in particular they will be applied here in cardiomyocytes to study the effects of PDP–PP1c. The results will provide the basis to fine-tune targeting PP1 for the treatment of heart insufficiency. Furthermore, the principles and methods developed here will be applicable more generally for defining the interaction scope of target-bound ligands (drugs) as well as for using PP1 as tool in synthetic biology.

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

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