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Studying the Spatio-temporal Regulation of Unperturbed Life and Death Cellular Processes : Easier Said than Done !

Lundi 15 octobre 2018 14:00 - Duree : 1 heure
Lieu : Conference room - LIPhy - Bât E - 140 Avenue de la Physique - St Martin d’Hères. Accès par interphone, appeler le secrétariat

Orateur : Franck B. RIQUET (VIB Inflammation Research Center, Ghent University, Ghent, Belgium)

Necroptosis is a caspase-independent cell death program involving RIPK1/RIPK3/MLKL that can be triggered by different stimuli like TNF. Necroptosis is involved in different pathologies such as ischemia-reperfusion injury, sepsis, inflammatory bowel diseases, multiple sclerosis, and even cancer. The rupture of the plasma membrane occurring in necroptosis releases immunogenic molecules that exert deleterious pro-inflammatory effects. Orientation of the cell death program towards apoptosis or necroptosis will have profoundly different outcomes, and it is therefore important to identify the conditions that modulate necroptosis. For example, ERK1/2 plays a role in various cell death modalities depending on the cellular context. ERK1/2 activity dynamics can be monitored at the single cell level using genetically-encoded FRET-based kinase activity reporter (KAR) such as EKAR-EV. However, saturation of KAR as well as slowness in reporting a decrease in kinase activity have been reported for EKAR-EV and JNKAR-EV, hampering the detection of the full kinase activity dynamics. To alleviate these shortcomings, we developed a method for accelerating the improvement of biosensor’s performance and produced an optimized version of EKAR-EV, named EKAR4.0. Using this novel biosensor, we investigated ERK1/2 spatio-temporal code in during apoptosis and necroptosis in single living L929 cells. Surprisingly, we observed amplitude- and frequency-modulated oscillatory patterns of ERK1/2 activity preceding cell death. Currently, we are analyzing the complex relationships between ERK1/2 and RIPK1/3-MLKL signaling pathways, leading to pro-death and pro-survival/inflammatory depending on the cell death program elicited.

Contact : Aurelie.Dupont@univ-grenoble-alpes.fr

Discipline évènement : (Biologie / Chimie)
Entité organisatrice : (LIPhy)
Nature évènement : (Séminaire)
Evènement répétitif : (Séminaire Mat. Molle/grise)
Site de l'évènement : Domaine Universitaire de St Martin d’Hères

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