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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.

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

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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