TRR 83:  Molecular Architecture and Cellular Functions of Lipid/Protein Assemblies

• Subject Area: Biology ; Medicine
• Term: from 2010 to 2021
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 112927078

The central aims of the TRR83 are to elucidate the molecular composition and structural organization of distinct membrane domains, to determine their physical and chemical properties and to understand their physiological functions. The TRR83 combines chemical biology, biochemistry, cell biology, lipidomics and advanced imaging techniques to discover and characterize lipid/protein assemblies. For example, novel functionalized analogs of distinct lipid species reveal their intracellular localization, photo-caged lipids are used to trigger spatio-temporally signal transduction cascades and crosslinkable lipids are employed to identify novel interaction partners. Lipid mass spectrometry has been further developed to identify novel lipids of unknown compositions. Making use of the recent progress in cryo-electron microscopy/tomography, TRR members will approach to gain structural insights into lipid/protein assemblies at the near atomistic level. Crystallography and molecular dynamics simulation will help to build structural models. Nano force measurements will lead to a quantitative biophysical understanding of protein-lipid interactions. The analysis of diverse physiological processes, such as viral budding, unconventional secretion, regulated exocytosis, endosomal fusion, plasma membrane organization, lipid transport at membrane contact sites, lipid metabolism and signaling shall reveal common and divergent principles underlying individual protein-lipid interactions. Thus, the combination of approaches will eventually lead to a comprehensive compositional and functional understanding of lipid/protein assemblies, revealing the biophysical principles and atomistic structures, which determine their stability and dynamics.

• DFG Programme: CRC/Transregios

Current projects

• Z - Central Tasks of the Transregional Collaborate Research Centre (Project Head Söllner, Thomas )

Completed projects

• 01 - Specific interactions of lipids with protein transmembrane segments (Project Heads Brügger, Britta ;  Wieland, Felix Wilhelm Theodor )
• 02 - Lipid localization and lipid-protein interaction studied in living cells (Project Head Schultz, Carsten )
• 03 - Lipid-protein interactions in rafts (Project Head Simons, Kai )
• 04 - High-resolution imaging the assembly and probing the interactions of human receptors in different sphingolipid-cholesterol assemblies (Project Head Müller, Daniel J. )
• 05 - Molecular machinery mediating FGF2 membrane translocation in unconventional secretion (Project Head Nickel, Walter )
• 06 - Prominin/membrane-lipid assemblies and their relevance for apical plasma membrane protrusions (Project Heads Corbeil, Denis ;  Huttner, Wieland B. )
• 07 - Characterization of saposins and saposin-dependent targets in inner lysosomal membranes of Drosophila (Project Heads Hoch, Michael ;  Sandhoff, Konrad )
• 08 - Molecular mechanisms of multivesicular body biogenesis (Project Head Hoflack, Bernard )
• 09 - Investigating the role of local curvature in recruiting membrane sculpting proteins in vitro (Project Head Schwille, Petra )
• 10 - The role of membrane microdomains in membrane fusion (Project Head Söllner, Thomas )
• 11 - Organization and function of SNARE domains (Project Head Lang, Thorsten )
• 12 - Reconstitution of lipid droplet function (Project Head Thiele, Christoph )
• 13 - Cellular and viral determinants of the hepatitis C virus replication and assembly compartment (Project Head Bartenschlager, Ralf Friedrich Wilhelm )
• 14 - Lipid composition of human immunodeficiency virus type 1 and its relevance for particle formation, stability and infectivity (Project Head Kräusslich, Hans-Georg )
• 15 - Membrane microdomain interactions of the HIV-1 pathogenicity factor Nef (Project Head Fackler, Ph.D., Oliver T. )
• 16 - Identification and functional characterization of protein associated with membrane fractions surrounding activating and inhibitory Natural Killer cell receptors (Project Head Watzl, Carsten )
• 17 - Shotgun lipidomics by high resolution tandem mass spectrometry (Project Head Shevchenko, Andrej )
• 18 - Regulation of cell signaling by inner leaflets (Project Head Coskun, Ünal )
• 19 - Patched-dependent regulation of intracellular endocannabinoid trafficking and its function in signalling and metabolism (Project Heads Eaton, Suzanne ;  Nadler, André Georg ;  Zerial, Ph.D., Marino )
• 20 - High resolution imaging of lipids (Project Heads Al-Amoudi, Ashraf ;  Kuerschner, Lars )
• 21 - Molecular dissection of anti-inflammatory effects of HDL (Project Head Latz, Eicke )
• 22 - Role of lipids in membrane protein insertion (Project Head Sinning, Irmgard )
• 23 - Synthetic endosomes (Project Head Zerial, Ph.D., Marino )
• 24 - Synthetic actomyosin-membrane cortex (Project Head Grill, Stephan Wolfgang )
• 25 - Lipid transport across membrane contact sites (Project Head Höglinger, Doris )
• 26 - Establishment of plasma membrane domain identity in epithelial cells (Project Head Honigmann, Alf )
• 27 - Measuring dynamics of native lipid species in living cells (Project Head Nadler, André Georg )
• 28 - Lipid-protein interaction in the primary cilium (Project Head Wachten, Dagmar )

• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Co-Applicant Institution: Rheinische Friedrich-Wilhelms-Universität Bonn; Technische Universität Dresden
• Participating Institution: Max-Planck-Institut für molekulare Zellbiologie und Genetik (MPI-CBG)
• Spokesperson: Professor Dr. Thomas Söllner