SFB 740:  From Molecules to Modules: Organisation and Dynamics of Functional Units in Cells

• Subject Area: Biology ; Medicine
• Term: from 2007 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 25065445

Our collaborative research project deals with the fundamental question how biological function, organization and complexity arise from interacting biological macromolecules. It has become increasingly clear during the past years that major reaction pathways in the living cell are carried out by macromolecules that work in a concerted manner and form interaction networks with a modular character. Accordingly, defined subsets of the macromolecules designated as "functional modules" (Hartwell et al., 1999) are responsible for specific cellular tasks. Time-ordered interactions and complex formation within these ensembles of macromolecules facilitate an autonomous function. Functional modules comprise two general types of entities, i.e. macromolecular machines, which are organized as compact structures, such as the ribosome or the proteasome, and more dynamic ensembles, which change their composition and/or organization during function, i.e. during vesicular transport or signal transduction. The SFB 740 is a concerted multidisciplinary effort devoted to an analysis of functional modules from a bottom-up perspective. Selected functional modules are studied with the tools of biophysics, biochemistry, and/or molecular and cell biology to obtain specific insights into the organization and functional mechanism of the various functional modules. Our analysis starts from the single macromolecules and their interactions to exemplify how modular function arises from macromolecular interactions and to yield the ¿design principles¿ of functional module. Our approach is complementary to top-down approaches from proteomics and systems biology and is thought to close the gap between the mere molecular point of view and the holistic systems view.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Dynamics of Genome Duplication Machines (Project Head Cardoso, Maria Cristina )
• A03 - Structure and dynamics eukaryotic 80S ribosomes during the elongation phase of protein synthesis (Project Head Spahn, Christian M. T. )
• A04 - The sub-module for spliceosome catalytic activation (Project Head Wahl, Markus C. )
• A05 - Dynamics of sub-modular and molecular interactions in translational elongation (Project Head Ignatova, Zoya )
• A06 - Structural basis of translation control in eukaryotic 80S ribosomes by phosphorylation of eS6 (Project Head Rappsilber, Juri )
• A07 - Acetylation of lysine 16 on histone H4 as a dynamic epigenetic mark during transcription and replication (Project Head Ehrenhofer-Murray, Ann Elizabeth )
• B01 - Functional and Structural Characterization of Heterotetrameric p97/ASPL complexes (Project Heads Heinemann, Ph.D., Udo ;  Wanker, Erich E. )
• B02 - Structural characterization of chaperone modulated protein aggregation in S. cervisiae (Project Head Reif, Bernd )
• B03 - Regulation of proteasome modules (Project Heads Kloetzel, Peter Michael ;  Krüger, Elke Beate )
• B04 - Structural and functional characterization of complex protein modules involved in regulation of proteasomal activitiy (Project Head Groll, Michael )
• B05 - Substrate recognition by the HRD-ubiquitin ligase (Project Heads Jarosch, Ernst ;  Sommer, Thomas )
• B06 - Structural elucidation of the GPCR allosteric machine (Project Heads Hildebrand, Peter ;  Scheerer, Patrick )
• B07 - Structural investigations of modules involved in protein homeostasis (Project Heads Oschkinat, Hartmut ;  van Rossum, Barth-Jan )
• B08 - Identification and characterization of a novel metazoan disaggregase module (Project Head Kirstein-Miles, Janine )
• C01 - Modular organisation of vesicle tethering to membranes: Analysis of structural features and regulation by protein palmitoylation (Project Heads Heinemann, Ph.D., Udo ;  Veit, Michael )
• C03 - Specific recruitment of viral components and assembly of enveloped viruses (Project Heads Herrmann, Andreas ;  Veit, Michael )
• C04 - Modular assembly, plasma membrane targeting and regulation of KCNQ (Kv7) K+ channels (Project Head Friedrich, Thomas )
• C05 - Modules involved in endosomal/lysosomal Ion homeostasis and function (Project Head Jentsch, Thomas J. )
• C07 - Structural and functional analysis of the dynamin module (Project Head Daumke, Oliver )
• C08 - Functional organization and dynamics of PI-kinase-based modules for protein sorting at endosomal membranes (Project Heads Haucke, Ph.D., Volker ;  Krauß, Michael )
• C09 - "Closing the cycle": Sub-modules in synaptic vesicle membrane targeting, fusion and endocytosis (Project Head Sigrist, Stephan J. )
• D01 - The regeneration-module in photoreceptor cells (Project Heads Heck, Martin ;  Hofmann, Klaus Peter )
• D02 - The circadian feedback module - assembly and localization as crucial events for circadian dynamics (Project Head Kramer, Achim )
• D03 - The modular function of the y-secretase in the generation of intermediate Aß species (Project Head Multhaup, Gerhard )
• D04 - Regulatory phosphorylation of scaffolding proteins of the inside-out-signaling complex (Project Heads Freund, Christian ;  Höfer, Thomas )
• D05 - The role of rhodopsin oligomers in the amplifier submodule of retinal rods (Project Heads Ernst, Oliver-Peter ;  Hofmann, Klaus Peter )
• D07 - Spatiotemporal simulation of module assembly and function (Project Head Noé, Frank )
• D08 - Spatial modeling of gradient sensing exemplified for the yeast pheromone response (Project Head Klipp, Edda )
• V01 - Central tasks (Project Heads Hofmann, Klaus Peter ;  Spahn, Christian M. T. )
• Z01 - Molecular electron microscopy (Project Heads Mielke, Thorsten ;  Spahn, Christian M. T. )

• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Co-Applicant Institution: Freie Universität Berlin; Humboldt-Universität zu Berlin
• Participating University: Technische Universität Berlin
• Participating Institution: Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP); im Forschungsverbund Berlin e.V.; Max-Delbrück-Centrum für Molekulare Medizin (MDC); Max-Planck-Institut für molekulare Genetik (MPIMG)
• Spokespersons: Professor Dr. Klaus Peter Hofmann, until 2/2011; Professor Dr. Christian M. T. Spahn, since 2/2011