
Introduction
The SFB 740 (Sonderforschungsbereich, Collaborative Research Centre) is a concerted interdisciplinary effort devoted to the analysis of functional modules, by definition molecular ensembleswith an autonomous function in cells (Hartwell et al., Nature 402, C47 (1999)). As specific subsets of the proteome, they are thought to bridge the gap between molecular detail and systems biology. Functional modules include the important group of macromolecular machines, which are organized as compact structure, such as the ribosome or the proteasome (Alberts, Cell 92, 291 (1998)), but also ensembles that change their composition and / or organisation during function – like G-protein coupled signal transducers. On receiving an input, modules go through functional cycles, in which they pass through different levels of complexity from the molecular to the modular level and back (Hofmann et al., Trends Biochem. Sci. 31, 497 (2006)). Characteristic properties include spatial sequestration and / or a characteristic time domain at which functional cycles proceed, and specific input / output schemes.
In 2010, the SFB has applied for further funding with researchers from seven institutions within greater Berlin (Charité, HU, FU, Potsdam University, MDC, FMP, MPI) and combines laboratories in experimental and theoretical biophysics, biochemistry, molecular biology and proteomics. The SFB comprises now 19 projects, 9 of which were newly applied for in 2010. Most of the new projects were incorporated to fill the gaps arising from the departure of many young principal investigators. They were intensely sought after by other universities, and six former PIs accepted offers from abroad. The criterion for the incorporation of a new project was the level of analysis rather than a specific biological system or methodology.
The projects are grouped in project areas A-D, dealing with (A) Nucleic acid processing during genetic information transfer, (B) Control of conformation and degradation of proteins, (C) Formation and transport of vesicles, and (D) Signal transduction. Within each project area, projects bridge the gap between the molecular detail and submodular or modular functions The current phase of our work in the SFB is marked by the consolidation and sharpening of the original concept and a number of new topics that developed during the work in the first funding period. We convinced ourselves that it is a reasonable approach, according to the original concept of the SFB, to start from an analysis of the single macromolecules and their interactions and explore to what extent we can reconstruct the behaviour of macromolecular assemblies. What we have in mind are ensembles with systemic character, which consist, however, of elements that are physically real objects in space and time, rather than abstract entities in interaction patterns or flow diagrams. During the first funding period, we saw numerous examples how decisive molecular details can be for the behaviour of whole modular ensembles. We are also getting a better appreciation of the importance of precise timing patterns, often set by GTPases. Other more recent general topics within the SFB are the variety in the mode of interaction (physical or via membrane potential) between the elements and submodular parts of a module and the shared usage of elements (parsimony or abundance).