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Group leader: Thierry Galli
INSERM Research Director (DR2)
E-mail: thierry.galli@inserm.fr
Phone: +33 1 57 27 80 39
Thierry Galli received his BSc in Biochemistry at the University Pierre and Marie Curie, Paris, in 1988, and his PhD at the Collège de France and the University Pierre and Marie Curie, Paris, in 1992. He then moved to the USA to carry out postdoctoral research in Professor Pietro De Camilli's laboratory at Yale University School of Medicine. There he worked on the molecular mechanism of regulated and constitutive exocytosis. In 1995, he took his first research appointment at the French National Institute of Health (INSERM) and the Curie Institute in the laboratory of Professor Daniel Louvard, and in 2001 he was recruited as Research Director of the French National Institute of Health at the Fer-à-Moulin Institute, Paris. In 2005, he was appointed as a Group Leader at the Jacques Monod Institute, Paris. His research focuses on the role of SNARE proteins in exocytosis mediating epithelial and neuronal cell differentiation, with particular emphasis on the tetanus neurotoxin-sensitive routes, mediated by cellubrevin and synaptobrevin, and the tetanus neurotoxin-insensitive routes mediated by TI-VAMP.
Biographical sketch.
Our projects
Membrane trafficking allows for the communication between the different membrane compartments of the biosynthetic and endocytic pathways and for the communication between cells and their environment through the secretion of signalling molecules by exocytosis and capture of nutrients by endocytosis. Exocytosis and endocytosis are crucial to maintain cell homeostasis and are also involved in differentiation and morphogenesis of cells.
Neuronal cell differentiation and de-differentiation of epithelial into mesenchymal cells represent two fundamental models of important cellular changes in shape and function. These two processes share common principles because both imply the presence of a domain specialized for cell movement at the leading edge of the cell, the axonal growth cone and the pseudopodium respectively.
Our working hypothesis is that exocytosis is responsible for the release and expression at the plasma membrane of proteins that are important for cell migration, outgrowth of axons and dendrites, formation and maintenance of cell-cell contacts (including synapses), and the repair and plasticity of neuronal and epithelial cells.
The aim of the team is to understand the basic mechanisms and the regulation of membrane trafficking in axonal outgrowth and epithelial cell migration. Our favorite molecules are the vesicular SNARE proteins Cellubrevin and TI-VAMP, and the adhesion protein Vezatin. We study the function of these proteins at the molecular, cellular and organism level.
We use classical techniques of cellular and molecular biology with special emphasis on live cell imaging and proteomics, as well as biophysical approaches to study membrane dynamics, adhesion and fusion in vitro. Our models include mutant mice, cultured neuronal and epithelial cells, and the reconstitution of proteins into artificial membranes.
Role of membrane trafficking in axonal outgrowth and neuronal differentiation
Thierry Galli, INSERM Research Director (DR2)
Phone: +33 1 57 27 80 39
(Illustration by Jean-Pierre Laigneau)
Biophysics of intracellular membrane fusion machineries (SNAREs and Mitofusins)
David Tareste, INSERM Researcher (CR1)
Phone: +33 1 57 27 80 38
(Illustration by Daniel de Fuenmayor)
Vezatin in epithelial and neuronal morphogenesis
Marie-Christine Simmler, CNRS Research Director (DR2)
E-mail: simmler.marie-christine@ijm.univ-paris-diderot.fr
Phone: +33 1 57 27 80 75
Selected publications
Bahloul A, Simmler MC, Michel V, Leibovici M, Perfettini I, Roux I, Weil D, Nouaille S, Zuo J, Zadro C, Licastro D, Gasparini P, Avan P, Hardelin JP, Petit C (2009) Vezatin, an Integral Membrane Protein of Adherens Junctions, is Required for Sound Resilience of Cochlear Hair Cells. EMBO Mol Med 1:128.
Chaineau M, Danglot L, Proux-Gillardeaux V, Galli T (2008) Role of Hrb in Clathrin Dependent Endocytosis. J Biol Chem 283:34365
Tareste D, Shen J, Melia TJ, Rothman JE (2008) SNAREpin/Munc18 Promotes Adhesion and Fusion of Large Vesicles to Giant Membranes. Proc Natl Acad Sci USA 105:2380
Li F, Pincet F, Perez E, Eng WS, Melia TJ, Rothman JE, Tareste D (2007) Energetics and Dynamics of SNAREpin Folding across Lipid Bilayers. Nat Struct Mol Biol 14:890
Proux-Gillardeaux V, Raposo G, Irinopoulou T, Galli T (2007) Expression of the Longin Domain of TI-VAMP Impairs Lysosomal Secretion and Epithelial Cell Migration. Biol Cell 99:261
Alberts P, Rudge R, Eirinopoulou T, Danglot L, Gauthier-Rouviere C, Galli T (2006) Cdc42 and Actin Control Polarized Expression of TI-VAMP Vesicles to Neuronal Growth Cones and their Fusion with the Plasma Membrane. Mol Biol Cell 17:1194
Scheuber A, Rudge R, Danglot L, Raposo G, Binz T, Poncer JC, Galli T (2006) Loss of AP3 Function Affects Spontaneous and Evoked Release at Hippocampal Mossy Fiber Synapses. Proc Natl Acad Sci USA 103:16562
Roux I, Safieddine S, Nouvian R, Grati M, Simmler MC, Bahloul A, Perfettini I, Le Gall M, Rostaing P, Hamard G, Triller A, Avan P, Moser T, Petit C (2006) Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse. Cell 127:277.
Announcements
Postdoctoral position available
A postdoctoral position in membrane fusion biophysics funded by the French Agency of National Research (2500€/month gross) is available at the Galli lab, in collaboration with Manuel Rojo’s team (Mitochondrial Dynamics and Organization, IBGC, Bordeaux). The project aims at elucidating the molecular mechanisms orchestrating the mitochondrial fusion machinery using in vitro reconstitution of candidate fusion proteins into various artificial lipidic platforms, combined with membrane imaging, adhesion and fusion assays (e.g. confocal imaging, FRET-based lipid mixing assay, giant liposomes micromanipulation). Applicants should hold a PhD in experimental physics or biophysics and be highly motivated by biological questions; a background in molecular and cellular biology, or a strong desire in acquiring it, will be appreciated. A minimum commitment for 2-3 years is desired, with a starting date during fall/winter 2009. To apply, please send a single PDF file that contains a CV, a short statement of research interests and experience, and three names of references with contact information to: david.tareste@inserm.fr. Learn more.
Address and directions
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Membrane Traffic in Neuronal and
Epithelial Morphogenesis (INSERM U950)
Program in Development and Neurobiology
Institut Jacques Monod (CNRS UMR 7592)
Université Denis Diderot - Paris 7
Bâtiment Buffon, 3rd floor, labo 316B
15 rue Hélène Brion, 75205 Paris Cedex 13, France
Office: +33 1 57 27 80 39
Lab: +33 1 57 27 80 37/38/40 |
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