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By definition a functional module is a subset of the cellular macromolecules that is required to fulfil an autonomous function. Central for the way a functional module achieves its task are the interactions between its macromolecular components, which are mostly proteins but can be also other macromolecules, e.g. RNA. One class of functional modules is organized around a stable macromolecular complex or machine. A second class of functional modules is built from a dynamic network of more transiently interacting macromolecules. The SFB applies for a third funding period with researchers from seven institutions within Berlin (Charité, HU, FU, TU, MDC, FMP, MPIMG) and combines laboratories in experimental and theoretical biophysics, biochemistry, molecular biology, cell biology and proteomics.
After we had significant exchanges in participating groups at the transition from the first to the second funding period, the composition of our SFB consolidated. In its current state, the SFB comprises 20 projects, 16 of which were active in the previous funding period. Three projects were discontinued, two of them because our principal investigators (PIs) accepted excellent offers by other universities outside Berlin. To compensate for these losses and to bring in new techniques, concepts and ideas added for four new projects (Ehrenhofer-Murray, Kirstein-Miles, Rappsilber, Sigrist). Three of these new projects (Ehrenhofer-Murray, Kirstein-Miles, Rappsilber) are by colleagues newly appointed to Berlin based institutions. The criterion for the incorporation of a new project was the level of analysis rather than a specific biological system or methodology. Our projects are grouped in the established project areas A-D like in the two previous funding periods. Our project areas are 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 area, the projects focus on the gap between the details of the molecular interactions and the modular functions.
Substantial progress was made in the various projects as seen by the list of project-related publications in internationally renowned journals. Collaborations among groups and combining technical expertise proved to be essential for our work on modular and submodular functions. Numerous and highly successful collaborations have been established, which can be seen by 27 joint publications co-authored by at least two PIs from different projects that emerged during the second funding period so far. Many of the joint publications appeared in high-impact journals including 6 papers in Nature, one paper in Cell and one review in Cell. Also all three theoretical projects (B6, D7, D8) established successful collaborations with experimental groups and are very well integrated in the SFB 740.
In our collaborative project, we wish to contribute to an understanding how the specific functions of modules arise from interactions among their macromolecular components to derive 'design principles' that govern the structure and function of modules. An overarching principle for example is the concept of a tuneable energy landscape with metastable states governing functional conformational dynamics in macromolecular assemblies as diverse as the ribosome, the dynamin superfamily or the G-protein coupled signalling mod-ule. Another recurring theme is the regulation of molecular/submodular events by intrinsically unstructured protein elements of module components as seen for spliceosome or signalling modules. Because we start from an analysis of the single macromolecules and their interactions, the approach pursued with the SFB 740 can be considered a bottom-up approach. Systems biology approaches often delineate abstract enti-ties in interaction patterns or flow diagrams. We, however, investigate ensembles that are of sufficient com-plexity to exhibit systemic character but, at the same time, are physically real objects in space and time. Thus, our collaborative project is entirely complementary to holistic top-down approaches pursued within proteomics or systems biology projects. We believe that in the frame of our concept and based on the strong progress in the individual projects and project areas, the SFB 740 is well prepared to continue highly productive work on one of the most challenging problems in life sciences.