11:30 – 12:00
Dr Yuval Elani: A toolkit for manufacturing an artificial cell from scratch: microfluidics, membrane design, and biomolecular engineering
12:00 – 13:00
Main Visiting Speaker – Dr Ludger Johannes: Lectin-driven and glycosphingolipid-dependent construction of endocytic pits for polarized protein distribution in cells
Abstract
Several endocytic processes do not require the activity of clathrin, and it has been a major question in membrane biology to know how the plasma membrane is bent and cargo proteins are sorted in these cases. Our previous studies have allowed us to propose the GL-Lect hypothesis: Nanodomain construction by GlycoLipid-binding cellular or pathological Lectins induces membrane curvature changes and drives the formation of tubular endocytic pits from which clathrin-independent carriers are generated for the cellular uptake of glycosylated membrane proteins (CD44, integrins…), pathogens (polyoma viruses, norovirus), or pathogenic factors (Shiga and cholera toxins). We are now analyzing how cortical actin dynamics contributes to the clustering of glycosphingolipid-lectin complexes on active membranes, thereby facilitating the nucleation of endocytic tubules exploiting membrane fluctuation force and asymmetric lipid compaction mechanisms that had not been linked before to endocytosis. Furthermore, we are identifying ways by which the GL-Lect mechanism is acutely controlled by growth factor signaling. Finally, we study how GL-Lect domain construction at the plasma membrane programs the intracellular distribution of cargo proteins via the retrograde transport route, thereby exploiting the polarized secretion capacity of the Golgi apparatus for the distribution of these cargoes to specialized plasma membrane domains in migrating cells (leading edge), epithelial cells (apico-basal sorting and transcytosis), and lymphocytes (immunological synapse). These studies are performed using a combination of cell biological (lattice light sheet microscopy), biochemical (membrane protein purification and reconstitution), and structural biology (cryo-EM) techniques on model membranes, in cells, and living organisms.
Biography
Ludger Johannes (PhD) is Research Director (DRE) at INSERM. Since the beginning of his biochemistry undergraduate studies in 1987, he is member of the Studienstiftung des Deutschen Volkes (German organization of the academically gifted), and since 1993 of Boehringer Ingelheim Fonds. Between 2001 and 2013, he directed the Traffic, Signaling and Delivery Team in the Cell Biology Department (UMR144 CNRS) of Institut Curie. Since January 2014, he is heading the Cellular and Chemical Biology unit (U1143 INSERM — UMR3666 CNRS). His research aims at establishing fundamental concepts of endocytosis and intracellular trafficking. The Johannes team has made two major contributions in this context: the discovery of a membrane trafficking interface between early endosomes and the Golgi apparatus, and the demonstration that dynamic lectin-induced glycosphingolipid reorganization acts as a driving force for endocytic pit construction in clathrin-independent endocytosis. These studies are highly cited and have been published in several highly visible journals, including Cell, Nature, Nature Cell Biology, and Nature Nanotechnology. He also aims at exploiting these discoveries in fundamental membrane biology research for the development of innovative cancer therapy strategies. His fundamental studies have allowed him to validate the B-subunit of Shiga toxin (STxB) as a “pilot” for the delivery of therapeutic compounds to precise intracellular locations of dendritic cells and tumors (10 patent families, 5 of which are delivered in the US, Europe and other countries; creation of biotech companies). Ludger Johannes serves on editorial boards of several international journals (including PLoS One and Traffic), and is EMBO member since 2012. His group is member of excellence initiative CelTisPhysBio, and he currently holds an ERC advanced grant (2014-2020).