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PyroPop SIGNED

Mechanisms and regulation of inflammasome-associated programmed cell death

Total Cost €

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EC-Contrib. €

0

Partnership

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 PyroPop project word cloud

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

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Project "PyroPop" data sheet

The following table provides information about the project.

Coordinator
JANSSEN PHARMACEUTICA NV 

Organization address
address: TURNHOUTSEWEG 30
city: BEERSE
postcode: 2340
website: www.janssenpharmaceutica.be

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 Belgium [BE]
 Total cost 1˙997˙915 €
 EC max contribution 1˙997˙915 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-01-01   to  2021-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    JANSSEN PHARMACEUTICA NV BE (BEERSE) coordinator 1˙321˙685.00
2    VIB VZW BE (ZWIJNAARDE - GENT) participant 676˙229.00

Map

 Project objective

Programmed cell death is essential for homeostasis, and its deregulation contributes to human disease. Inflammasome-induced pyroptosis of infected macrophages contributes to host defense against infections, but the concomitant release of inflammatory danger signals and leaderless cytokines is detrimental in chronic inflammatory diseases. The central hypothesis of the PyroPop ERC Consolidator project is that inflammasomes are cytosolic platforms that couple pathogen sensing to multiple programmed cell death modes. This is based on our preliminary data showing that inflammasomes can be triggered to switch from inflammatory pyroptosis to programmed necrosis and non-inflammatory apoptosis. This suggests that the (patho)physiological outcomes of inflammasome activation may be modulated for therapeutic purposes. However, the molecular machinery and effector mechanisms of pyroptosis, inflammasome-induced apoptosis and programmed necrosis are virtually unknown. My objectives are (i) to explore the cleavage events and subcellular dynamics of pyroptosis by proteomics and high-resolution time-lapse microscopy; (ii) to clarify the molecular mechanisms of pyroptosis and inflammasome-controlled cell death switching; and (iii) to address how inflammasome-associated cell death modes impact on anti-bacterial host defense and chronic inflammatory pathology in vivo through the identification of pyroptosis-selective biomarkers and clinical analysis of pyroptosis-deficient mouse models. The central hypothesis in this regard is that inflammasome-mediated secretion of leaderless cytokines (such as IL-1β and IL-18) and danger signals may be mechanistically coupled to pyroptosis, but not apoptosis induction. By clarifying the mechanisms of inflammasome-controlled programmed cell death, this project may set the path for the development of an entirely novel class of inflammation-modulating therapies that are based on converting inflammatory pyroptosis into non-inflammatory apoptosis.

 Publications

year authors and title journal last update
List of publications.
2017 Nina Van Opdenbosch, Hanne Van Gorp, Maarten Verdonckt, Pedro H.V. Saavedra, Nathalia M. de Vasconcelos, Amanda Gonçalves, Lieselotte Vande Walle, Dieter Demon, Magdalena Matusiak, Filip Van Hauwermeiren, Jinke D’Hont, Tino Hochepied, Stefan Krautwald, Thirumala-Devi Kanneganti, Mohamed Lamkanfi
Caspase-1 Engagement and TLR-Induced c-FLIP Expression Suppress ASC/Caspase-8-Dependent Apoptosis by Inflammasome Sensors NLRP1b and NLRC4
published pages: 3427-3444, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2017.11.088
Cell Reports 21/12 2019-06-18
2019 Nina Van Opdenbosch, Mohamed Lamkanfi
Caspases in Cell Death, Inflammation, and Disease
published pages: 1352-1364, ISSN: 1074-7613, DOI: 10.1016/j.immuni.2019.05.020
Immunity 50/6 2019-09-05
2019 Hanne Van Gorp, Mohamed Lamkanfi
The emerging roles of inflammasome‐dependent cytokines in cancer development
published pages: , ISSN: 1469-221X, DOI: 10.15252/embr.201847575
EMBO reports 20/6 2019-09-05

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

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