Research unit 2743 - mechanical stress protection
Cell survival, tissue integrity and organismal health depend on the ability to maintain functional protein networks even under conditions that threaten protein integrity. Protection under such stress conditions involves the adaptation of folding and degradation machineries, which help to preserve the protein network and facilitate the refolding or disposal of damaged proteins.
In multicellular organisms, cells are permanently exposed to stress resulting from mechanical forces and their homeostasis relies on dedicated stress protection systems. Mechanical stress protection operates during cell differentiation, adhesion and migration, and is of particular importance for maintaining tissues such as skeletal muscle, heart, lung, kidney, skin and vasculature. Yet, underlying molecular mechanisms have not been comprehensively studied.
In an unprecedented multi-disciplinary approach, the research unit combines mechano- and cell biology, kidney, muscle and exercise physiology, molecular immunology and worm and mouse genetics. State-of-the-art technology will be used to apply mechanical stress in a highly defined manner to isolated cells and tissues, genetically tractable model organisms and human subjects. Force-induced alterations of protein folding and degradation machineries will be investigated through biochemical, cell biological, proteomic and genetic methods. This will allow us to identify chaperone and degradation systems dedicated to the handling of mechanically unfolded and damaged proteins, and to elucidate the regulation of these systems under mechanical stress.
The research unit will establish fundamental principles of mechanical stress protection in multicellular organisms and will reveal the relevance of these processes for diseases such as muscle weaknesses, immune deficiencies and kidney failure.
After an initial three years of funding, the research unit was granted an extension by the Deutsche Forschungsgemeinschaft in July 2021. We very much appreciate the opportunity to continue our research on mechanical stress protection.
