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

• 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
• 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

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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.