PyroPop SIGNED
Mechanisms and regulation of inflammasome-associated programmed cell death
Total Cost €
0EC-Contrib. €
0Partnership
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Explore the words cloud of the PyroPop project. It provides you a very rough idea of what is the project "PyroPop" about.
Project "PyroPop" data sheet
The following table provides information about the project.
| Coordinator |
JANSSEN PHARMACEUTICA NV
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 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 inflammasomeâ€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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