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inCITe SIGNED

Seeing Citrulline: A Molecular Toolbox for Peptidyl Arginine Deiminases

Total Cost €

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EC-Contrib. €

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Partnership

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 inCITe project word cloud

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

interdisciplinary    molecules    world    pathological    peptidyl    last    templated    biology    isotype    rheumatoid    isotypes    specificity    lacking    arginine    antibodies    insights       thereby    avidity    substrate    strategies    reflects    leads    inhibitor    exact    unprecedented    selective    strategy    questions    inhibitors    centring    arthritis    levels    therapeutic    of    pad    erosion    suggest    explore    experiences    fundamental    autoimmune    unanswered    evolution    causing    destruction    unknown    ra    enzymes    ambition    isoform    discovery    conflicting    answer    excluding    deiminase    dysregulation    protein    population    chemical    disease    functioning    citrulline    mechanism    neoepitopes    roughly    wellbeing    nanosponges    immunology    patients    workpackages    innovative    intracellular    bone    modulators    citrullination    hampering    mediated    devastating    activation    affinity    onset    health    molecular    cartilage    diseases    eraser    evidences    substrates    citrullinated    tools    multifunctional    enzyme    nanomedicine   

Project "inCITe" data sheet

The following table provides information about the project.

Coordinator
STICHTING KATHOLIEKE UNIVERSITEIT 

Organization address
address: GEERT GROOTEPLEIN NOORD 9
city: NIJMEGEN
postcode: 6525 EZ
website: www.radboudumc.nl

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 Netherlands [NL]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-STG
 Funding Scheme ERC-STG
 Starting year 2019
 Duration (year-month-day) from 2019-01-01   to  2023-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    STICHTING KATHOLIEKE UNIVERSITEIT NL (NIJMEGEN) coordinator 1˙500˙000.00

Map

 Project objective

Roughly 1% of the world’s population is affected by rheumatoid arthritis (RA); a devastating autoimmune disease causing cartilage destruction and bone erosion. Recent evidences suggest that dysregulation of Peptidyl Arginine Deiminase (PAD) levels are associated with the onset of the disease, leading to the production of antibodies targeting the citrullinated neoepitopes. The exact role of each of the PAD isotypes in these pathological processes is unknown and fundamental questions on the intracellular activation mechanism and substrate specificity remain unanswered. Moreover, isoform specific and high affinity enzyme inhibitors are lacking thereby not only hampering fundamental research towards each PAD isotype, but also excluding PAD as a potential therapeutic target for these diseases. This proposal is aimed at developing innovative chemical biology- and molecular tools to study PAD functioning and protein citrullination in health and disease. The work reflects my interdisciplinary experiences as well as my interest I have obtained over the last years in chemical immunology as well as my ambition to improve patients wellbeing. More detailed, I aim to 1) find unknown PAD modulators, 2) find PAD substrates, 3) find selective and high affinity PAD inhibitors using enzyme-templated inhibitor evolution as novel lead discovery strategy, 4) explore multifunctional targeted PAD ‘nanosponges’ as advanced avidity-based nanomedicine approach and 5) explore unprecedented citrulline ‘eraser’ enzymes by innovative chemical biology strategies. The workpackages described in this ambitious and highly interdisciplinary proposal deliver high-end molecules and methods that can be used to answer fundamental (conflicting) questions on citrullination and PAD biology. Moreover, possible molecular leads and advanced therapeutic insights are provided thereby centring PAD as therapeutic target for citrulline-mediated autoimmune diseases such as RA.

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

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