SFB 958:  Scaffolding of Membranes: Molecular Mechanisms and Cellular Functions

• Subject Area: Biology ; Medicine
• Term: from 2011 to 2023
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 184695641

Membrane-based protein scaffolds are typically dynamic, metastable structures, which form an avidity-based multicomponent matrix. Work by SFB 958 has revealed that their spatiotemporally controlled assembly and disassembly plays crucial roles in membrane traffic and remodeling, cell signaling, as well as in differentiation and development. The combined multidisciplinary approaches within SFB 958 have and will lead to the identification and extraction of generic molecular mechanisms by which dynamically organized protein-protein assemblies scaffold cellular membranes. This results in an improvement of our understanding of how they exert their cellular and, consequently, organismal functions.Within SFB 958, we investigate scaffolds across a spectrum of biological entities and dynamic processes, ranging from cell signaling and sensory transduction to intracellular transport and mechano-transduction. Researchers of SFB 958 have implemented new and cutting-edge “enabling” techniques, such as various forms of super-resolution light microscopy, cryo-electron tomography and multiple physiological assays. The study of such complex biological systems will allow us to assess whether the general principles derived from the analysis of membrane scaffolds in molecularly well-defined cell-based settings can explain and, possibly, predict biological function at higher levels. We recognize that theoretical modeling is of increasing importance for a thorough understanding of scaffolding mechanisms. To strengthen this area of we have included Michael Kozlov, a world-leading theoretician from Tel Aviv University (Israel), who has pioneered the study of membrane/protein ensemble dynamics by theoretical biophysical approaches, in to the consortium. Moreover, the recent progress in cryo-electron microscopy is reflected by the new Z05 project led by Christian Spahn, a leading cryo-electron microscopist. Lastly, we have included two additional projects led by newly recruited junior faculty Francesca Bottanelli and David Owald into the consortium.These changes in the structure of the consortium together with the cutting-edge technologies and expertise gathered within the SFB during the previous funding periods will enable us to achieve the ambitious goals detailed in the application that will lead to a refined molecular understanding of the scaffolds under study.

• DFG Programme: Collaborative Research Centres
• International Connection: Israel

Completed projects

• A01 - Structural and functional organization of endocytic scaffolds within the periactive zone (Project Heads Haucke, Ph.D., Volker ;  Maritzen, Tanja )
• A02 - Molecular and cellular mechanisms of myoblast fusion (Project Heads Birchmeier, Carmen ;  Schmoranzer, Jan )
• A03 - In vivo analysis of active zone assembly (Project Heads Petzoldt, Astrid G. ;  Sigrist, Stephan J. )
• A04 - Spatiotemporal model of neuronal signaling and its regulation by presynaptic membrane scaffolds (Project Heads Clementi, Ph.D., Cecilia ;  Noé, Frank )
• A05 - The role of the RIM-binding protein active zone scaffold in regulating neurotransmitter release at diverse central synapses (Project Heads Rosenmund, Christian ;  Schmitz, Dietmar )
• A06 - Organization of the synaptic active zone scaffold by Bruchpilot and RIM-binding protein (Project Heads Sigrist, Stephan J. ;  Wahl, Markus C. )
• A07 - Regulation of SH3 domain-based scaffolds in clathrin-mediated endocytosis (Project Heads Freund, Christian ;  Haucke, Ph.D., Volker )
• A08 - Sorting of VGLUT between vesicular and plasma membrane compartments: role of endocytic protein scaffolds and their impact on synaptic transmission (Project Heads Ahnert-Hilger, Gudrun ;  Schmitz, Dietmar )
• A09 - Scaffolding of mechanotransduction domains in migrating and non-migrating cells (Project Heads Hammes-Lewin, Annette E. ;  Lewin, Ph.D., Gary Richard ;  Poole, Kathryn )
• A10 - Functional investigation of odorant receptor-assiciated scaffolding protein complexes in olfactory neurons (Project Head Neuhaus, Eva Maria )
• A11 - Functional analysis of septin scaffolds assembled at the plasma membrane during cytokinesis (Project Heads Daumke, Oliver ;  Ewers, Helge ;  Krauß, Michael )
• A12 - Structural and functional examinations of nucleotide-dependent membrane scaffolds (Project Heads Daumke, Oliver ;  Spahn, Christian M. T. )
• A13 - Golgi-associated protein scaffolds regulating receptor targeting and hormone secretion (Project Head Schürmann, Annette )
• A15 - Functions of c-Cbl and Hakai-based endocytic scaffolds in trafficking of cell surface receptors (Project Heads Birchmeier, Walter ;  Selbach, Matthias )
• A16 - A PRG2-PTEN based membrane scaffold involved in the formation of axon branches (Project Head Eickholt, Britta )
• A17 - Protein scaffolds in synaptic endomembrane degradation (Project Head Hiesinger, Peter Robin )
• A18 - Synaptic scaffold proteins regulate presynaptic proteostasis (Project Heads Garner, Craig C. ;  Schmitz, Dietmar )
• A19 - Functional regulation of postsynaptic scaffold proteins (Project Heads Shoichet, Sarah A. ;  Wahl, Markus C. )
• A20 - Septin-dependent compartmentalization of BMP2-signaling in cell migration (Project Heads Ewers, Helge ;  Knaus, Petra )
• A21 - A global role of alternative splicing in the secretory pathway: The COPII scaffold and beyond (Project Head Heyd, Florian )
• A22 - Investigating the role of the membrane-associated Cerebral Cavernous Malformations (CCM) protein scaffold in biomechanical signaling (Project Head Seyfried, Salim )
• A23 - Characterization of the membrane scaffold complexes that tune photoreceptor neuron function (Project Head Wernet, Mathias )
• A25 - Nanoscale organization of adaptor scaffolds involved in polarized cargo sorting at the trans-Golgi network (TGN) (Project Head Bottanelli, Ph.D., Francesca )
• A26 - Modelling mechanisms of membrane shaping, fusion, and fission in endo- and exocytosis by protein scaffolds (Project Head Kozlov, Ph.D., Misha )
• A27 - Synaptic scaffolds regulating cholinergic Drosophila synapses (Project Head Owald, David )
• MGK - Integrated Research Training Group (Project Heads Ewers, Helge ;  Knaus, Petra ;  Krauß, Michael )
• Z01 - Central Tasks-SFB Headquarters and Administration (Project Heads Haucke, Ph.D., Volker ;  Sigrist, Stephan J. )
• Z02 - Advanced and super-resolution imaging to resolve the nanoscale structure and dynamics of membrane scaffolds (Project Heads Ewers, Helge ;  Schmoranzer, Jan )
• Z03 - Proteomics platform for protein interaction mapping (Project Heads Freund, Christian ;  Liu, Fan ;  Multhaup, Gerhard ;  Weise, Christoph )
• Z04 - Proteomic analysis (Project Head Bordignon, Enrica )
• Z05 - Three-dimensional cryo-electron microscopy (Project Head Spahn, Christian M. T. )
• Ö - Reflecting on the nature of science using examples from the SFB 958 (Project Heads Krüger, Dirk ;  Skiebe-Corrette, Petra )

• Applicant Institution: Freie Universität Berlin
• Participating Institution: Charité - Universitätsmedizin Berlin; Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE); Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP); im Forschungsverbund Berlin e.V.; Max-Delbrück-Centrum für Molekulare Medizin (MDC); Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE); c/o Charité - Universitätsmedizin Berlin
• Participating University: Tel Aviv University; Universität Potsdam
• Spokespersons: Professor Volker Haucke, Ph.D., until 9/2012; Professor Dr. Stephan J. Sigrist