Research Area B

Composition and Dynamics of Macromolecular Complexes in Quality Control and Signaling

Integration, amplification and distribution of external and internal signals regulate cellular processes through interaction of many different macromolecular complexes. The localisation and composition of signalling complexes are dynamically regulated by post-translational modifications exerting quality control at the levels of individual molecules, organelles and even cells. CEF scientists studied the structure and function of key complexes that are involved in three important steps, namely in dedicated quality control processes, in intracellular signal transduction and in transcription. The role of phosphorylation and ubiquitylation in cellular quality control pathways is well established, but several novel functions in organellar and cellular quality mechanisms have been identified during the first funding phase of the Cluster. CEF scientists then focussed on deciphering the role of ubiquitylation and other ubiquitin-like modifications as dynamic molecular switches between cell death and survival as well as autophagic removal of large protein aggregates and misfunctional organelles. They discovered a general mechanism of how phosphorylation of cargo-selective receptors can control autophagic clearance of different cargoes. They investigate the mechanisms of selective autophagy of protein aggregates and pathogens in this research area (and mitochondria and ribosomes in research areas A and C, respectively). At the nuclear level, the composition and dynamics of transcriptional complexes and chromatin remodeling factors are essential for cellular functions. How these dynamic signals regulate oligomerization and activity of TAp63, a quality control factor of the female germ line, and the assembly of large leukemia-related transcriptional complexes and their role in physiological and pathophysiological conditions was also studied in the second funding phase. Impacts of CEF research include quantitative parameters of macromolecular interactions in cells as well as spatio-temporal regulation of signaling networks and quality control mechanisms.