SFB 969: Chemical and Biological Principles of Cellular Proteostasis

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Proteostasis comprises multiple highly conserved and interconnected cellular processes that control the activity of individual proteins in space and time to ensure the functionality of the proteome, its continuous renewal, and its adaptation to environmental changes. At the posttranscriptional level, three main aspects of proteostasis can be defined: Protein biogenesis including translation, folding, transport, and assembly processes; Modulation of protein function, concentration, and localization by posttranslational modification; Protein quality control to recycle or remove misfolded or aggregated proteins to avoid accumulation of toxic products inside the cell. It is known that proteostasis naturally declines during aging or can reach its limits by extreme challenges. The profound consequence of a decline of cellular proteostasis for the entire organism is highlighted by the fact that many human diseases including cancer and neurodegenerative disorders are caused by misregulation of protein activities.To dissect the principles underlying proteostasis, the Collaborative Research Center (CRC) 969 combines, in a highly interdisciplinary and synergistic research approach, the expertise of Chemistry and Biology in order to:(i) understand the regulation of individual protein activities that act at cellular hubs of proteostasis, e.g. in protein folding and assembly, posttranslational modification, and protein degradation. (ii) study processes and mechanisms required to adapt the proteome to specific demands such as metabolic changes, cell division, viral infection, and stress.(iii) develop novel chemical tools and biophysical strategies to simulate, monitor or manipulate protein activities and thereby proteostasis in vitro and in vivo. Research in the CRC 969 carried out in 19 projects centers around three research areas reflecting the life cycle of proteins and thus the key pathways of proteostasis: (A) Protein Biogenesis, (B) Protein Modification, and (C) Protein Aggregation and Degradation.