Welcome on the Necker-Enfants Malades Institute website

from basic science:
to the translational research:
Etienne Morel

Focus

The main focus of our research team is to understand how mammalian cells organelles and endomembranes cooperate with autophagic machinery to adapt to stress situations and external stimuli.

Introduction

Most of mammalian intracellular compartments are highly regulated and renewed to ensure that complex trafficking and sorting functions occur properly and maintain normal cell physiology. In this dynamic context, the intracellular degradative autophagy pathway probably takes advantages of – and initiates dialogs with - pre-existing signaling platforms, organelles and endomembranes. Although there is low-level basal activity, autophagy is mostly associated with stress responses and is considered as an acute protective system that ensures cell homeostasis and contributes directly to cell metabolism and energy regulation. Accordingly, autophagy participates in development, immunity and protects against cell modifications related to ageing. Autophagy involves the formation, and subsequent trafficking, of autophagosomes, which arise from the closure of transient cup-shaped double-membrane structure termed phagophore that capture cytoplasmic cargos for a final delivery to lysosomes. Studying the crosstalk of autophagic machinery with other cellular organelles and structures, such as mitochondria, endosomes and primary cilia, will shed light on the importance of endomembranes and signaling platforms cooperation in stress sensing and homeostasis regulation in a wide variety of mammalian cells.

Research objectives

Our project aims at investigating the cellular and molecular mechanisms that regulate autophagic pathway during stress response in cooperation with other endomembranes, in physiological and pathophysiological situations.

More precisely, three interconnected axes are currently investigated in my laboratory:

  1. membrane dynamics and coordination during autophagosome biogenesis, from scaffolding and cytoskeleton complexes implication to membrane contact sites machineries mobilization.
  2. autophagy and endosomes interdependancy and dialog in cell surface receptors signalization regulation, in normal and pathological situations.
  3. autophagic machinery mobilization in cellular homeostasis regulation, by direct/indirect relationship with the cellular stress sensor primary cilium structure and signaling platforms.

5 main publications

  • The primary cilium protein folliculin is part of the autophagy signalling pathway
    to regulate epithelial cell size in response to fluid flow
    Zemirli N*, Boukhalfa A*, Dupont N, Botti J, Codogno P and Morel E
    Cell Stress, 2019 Feb
  • Local detection of PI3P at autophagosome biogenesis membrane platforms
    Nascimbeni AC, Codogno P and Morel E.
    Autophagy, 2017 Sept
  • ER-plasma membrane contact sites contribute to autophagosome biogenesis
    by regulation of local PI3P synthesis
    Nascimbeni AC, Giordano F, Dupont N, Grasso D, Vaccaro MI, Codogno P and Morel E.
    EMBO Journal, 2017 May
  • Autophagosomes contribute to Intracellular Lipid distribution in Enterocytes
    Khaldoun SA, Emond-Boisjoly MA, Chateau D, Carrière V, Lacasa M, Rousset M, Demignot S and Morel E.
    Molecular Biology of the Cell, 2014 Jan
  • PI3P Regulates Sorting and Processing of Amyloid Precursor Protein through the Endosomal System
    Morel E, Chamoun Z, Lasiecka ZM, Chan RB, Williamson R, Vetanovetz C, Dall’Armi C, Simoes S, Point du Jour KS, McCabe B, Small SA and Di Paolo G.
    Nature Communications, 2013 Aug

2019

  • Interplay between primary cilia, ubiquitin-proteasome system and autophagy.
    Boukhalfa A*, Miceli C*, Ávalos Y, Morel E# and Dupont N#.
    Biochimie 2019 July

  • The primary cilium protein folliculin is part of the autophagy signalling pathway to regulate epithelial cell size in response to fluid flow
    Zemirli N*, Boukhalfa A*, Dupont N, Botti J, Codogno P and Morel E
    Cell Stress 2019 Feb

  • Autophagy is required for memory formation and reverses age-related memory decline
    Glatigny M*, Moriceau S*, Ramos-Brossier M*, Nascimbeni AC, Shanley MR, Rivagorda M, Boudarene N, Rousseaud A, Settembre C, Kuperwasser N, Friedlander G, Friedman AK, Morel E, Codogno P and Oury F.
    Current Biology 2019 Jan
  • 2018

  • A novel regulator of autophagosome biogenesis and lipid droplet dynamics
    Morel E and Codogno P.
    EMBO Reports 2018 Sept

  • FOXO3a provides a quickstep from autophagy inhibition to apoptosis in cancer therapy
    Codogno P and Morel E.
    Developmental Cell 2018 Mar

  • Mitochondrial dynamics in basal and stressful conditions
    Zemirli N, Morel E and Molino D.
    International Journal of Molecular Science 2018 Feb

  • Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells
    Morel E, Ghezzal S, Lucchi G, Truntzer C, Pais de Barros JP, Simon-Plas F, Demignot S, Mineo C, Shaul PW, Leturque A, Rousset M and Carriere V.
    BBA Molecular And Cellular Biology of Lipids 2018 Feb
  • 2017

  • ER-driven membrane contact sites: evolutionary conserved machineries for stress response and autophagy regulation?
    Molino D, Nascimbeni AC, Giordano F, Codogno P and Morel E.
    Communicative & Integrative Biology 2017 Dec

  • To be or not be cell-autonomous? Autophagy says both
    Fenouille N, Nascimbeni AC, Botti-Millet J, Dupont N, Morel E and Codogno P
    Essays in Biochemistry 2017 Dec

  • Local detection of PI3P at autophagosome biogenesis membrane platforms
    Nascimbeni AC, Codogno P and Morel E.
    Autophagy 2017 Sept

  • Autophagosomal membranes assemble at ER-plasma membrane contact sites
    Nascimbeni AC, Codogno P and Morel E.
    Molecular and Cellular Oncology 2017 July

  • ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis
    Nascimbeni AC, Giordano F, Dupont N, Grasso D, Vaccaro MI, Codogno P and Morel E.
    EMBO Journal 2017 May

  • PI3P in the regulation of autophagy membrane dynamics
    Nascimbeni AC, Codogno P and Morel E.
    FEBS Journal 2017 May

  • The biogenesis of autophagosome: a new challenge for the cell biologist
    Morel E.
    Médecine/Sciences 2017 Mar

  • The journey of the autophagosome through mammalian cell organelles and membranes
    Molino D, Zemirli N, Codogno P and Morel E.
    Journal of Molecular Biology 2017 Feb

  • Autophagy: a Druggable Process
    Morel E, Mehrpour M, Botti J, Dupont N, Hamaï A, Nascimbeni AC and Codogno P.
    Annual Reviews in Pharmacology and Toxicology 2017 Jan

  • Molecular mechanisms of non-canonical autophagy
    Dupont N, Nascimbeni AC, Morel E, and Codogno P.
    International Review of Cell and Molecular Biology 2017 Jan
  • My main interest in biology concerns intracellular compartments membrane dynamics, trafficking and interconnections. After a PhD in Physiology and Cell Biology at Pierre et Marie Curie Paris 6 University (2003), I specialized myself on endosomal membrane dynamics (Postdoc #1 (2004-2009), University of Geneva, Dept of Biochemistry, Geneva, CH) and on biology of phosphoinositides on endosomal features of Alzheimer’s disease (Postdoc #2 (2009-2010), Columbia University, Cell Biology and Pathology Dept, NYC, USA). After having a permanent position at Inserm, I studied the role of autophagy in alimentary lipids behavior in human enterocytes (Centre de Recherches des Cordeliers (2010-2013), Paris) and I finally joined the Cell Biology department of Institut Necker Enfants Malades in 2014 to develop projects on basic autophagy in the context of stress sensing. The research goal of my team is to understand how mammalian cells organelles cooperate with autophagic machinery to respond to stress stimuli.

    Permanent researcher
    Joëlle Botti
    -
    +33 (0)1 40 61 54 01
    Nicolas Dupont
    -
    +33 (0)1 40 61 54 02
    Etienne Morel
    Researcher
    +33 (0)1 72 60 64 74
    PhD
    Asma Boukhalfa
    PhD Student
    +33(0)1 40 61 54 03
    Irene Pila-Castellanos
    PhD Student
    +33(0)01 72 60 64 74
    Frederica Roccio
    PhD Student
    +33 (0)1 40 61 54 03
    Student
    Lynda Agharmiou
    Graduate student
    +33 (0)1 40 61 54 04
    Emeritus
    Patrice Codogno
    -
    +33 (0)1 72 60 64 76
    Address

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    Support(s)
    HRH Princess Caroline of Hanover, who through the Princess Grace Foundation, already supports medical research and anything that helps to relieve the sick children in France and around the world, has agreed to commit to our side so that our Center of Molecular medicine continues to meet the current challenges and fight diseases, and in particular the ones affecting children.

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