Focus

The main focus of our research team is to understand how mammalian cells mobilize organelles, endomembrane-based signaling platforms and autophagic machinery to adapt to stress situations and external stimuli.

More information / follow us on:
https://www.researchgate.net/lab/Etienne-Morel-Lab-autophagy-pathway-and-intracellular-membrane-dynamics-Etienne-Morel

https://twitter.com/MorelLab4

Introduction

Mammalian intracellular compartments are highly regulated and renewed to ensure the maintaining of proper 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.

3 interconnected axes are currently investigated in my laboratory:

1. Space and time orchestration of autophagy associated membrane dynamics processes: roles of phosphoinositides and lipid-kinases, scaffolding proteins, cytoskeleton and membrane contact sites
2. Cannonical and non-cannonical functions of autophagic machinery during the crosstalk with the primary cilium
3. Non-cell autonomous functions of mechanical stress induced autophagy in kidney epithelial cells differentiation and metabolism, in normal and pathological situations

Keywords: autophagic membranes and machinery, chemical, nutritional, infectious and mechanical stresses, primary cilium, endosomes, mitochondria, metabolism, membrane dynamics and contact-sites.

5 main publications

• Chemical targeting of NEET proteins reveals their function in mitochondrial morphodynamics
  Molino D*, Pila-Castellanos I*, Marjault HB, Amoedo ND, Kopp K, Rochin L, Karmi O, Sohn YS, Lines L, Hamaï A, Joly S, Radreau P, Vonderscher J, Codogno P, Giordano F, Machin P, Rossignol R, Meldrum E, Arnoult D, Ruggieri A, Nechushtai R, De Chassey B and Morel E
  EMBO Reports 2020 Nov
• The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation of kidney epithelial cells
  Miceli C*, Penalva-Mousset L*, Roccio F*, Burtin M, Leroy C, Nemazanyy I, Friedlander G, Morel E, Terzi F, Codogno P and Dupont N
  Nature Cell Biology, 2020 Aug
• PI3KC2α-dependent and VPS34-independent generation of PI3P controls primary cilium-mediated autophagy in response to shear stress
  Boukhalfa A*, Nascimbeni AC*, Ramel D, Dupont N, Hirsch E, Gayral S, Laffargue M#, Codogno P and Morel E
  Nature Communications, 2020 Jan
• 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

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My main interest in biology concerns intracellular compartments membrane dynamics, trafficking and interconnections. I obtained my PhD in Physiology and Cell Biology at Pierre et Marie Curie Paris 6 University (2003) and then 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 then 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.

https://sbcf.fr/member/etienne-morel/