FOR 5762:  Cell Non-Autonomous Regulation of Organismal Proteostasis

• Subject Area: Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 531902955

Protein homeostasis (or proteostasis) is essential for cellular and organismal viability. Proteostasis is achieved by an evolutionary conserved network of quality control pathways that orchestrate the biogenesis of correctly folded proteins, prevent proteins from misfolding, and remove potentially harmful proteins through selective degradation. However, the proteostasis network has a limited capacity, and its deterioration leads to the accumulation of damaged proteins that impair cellular function and organismal viability, causing metabolic, oncological, and neurodegenerative disorders. Because the proteostasis network is constantly challenged by ever-changing metabolic, environmental, and pathological conditions, maintaining a healthy proteome in all tissues is a lifelong challenge for organisms. Moreover, cells lose their proteostasis capacity during aging, including a generalized downregulation of chaperones and protein degradation machineries. While cell-autonomous quality control mechanisms have been extensively studied, recent evidence demonstrates systemic coordination of proteostasis between different tissues. These findings suggest the existence of cell non-autonomous communication pathways that integrate and balance proteostasis mechanisms across tissues to maintain the organismal proteome. Traditional studies in historically separate fields have addressed individual quality control pathways rather than the systemic coordination and rewiring between proteostatic nodes. This Research Unit initiative aims to define the dynamic regulation of organismal quality control pathways that integrate environmental and metabolic changes. The detailed analysis of cell non-autonomous coordination mechanisms will allow us to construct a global picture of the conserved inter-organ networks required to safeguard the organismal proteome in health and disease. Our interdisciplinary Research Unit will combine biochemical, cell biological, (opto)-genetic, and proteomics approaches to define the intertissue mechanisms underlying the regulation of organismal proteostasis under different physiological and pathological conditions. This timely initiative builds on a highly collaborative academic environment at the University of Cologne (UoC), strengthened by strategic hires and substantial investments, paving the way for the development of an internationally visible center for proteostasis research.

• DFG Programme: Research Units

Projects

• Cell non-autonomous alterations of neuronal proteostasis in neurodegeneration (Applicant Dudanova, Ph.D., Irina )
• Cell-non-autonomous control of kidney podocyte proteostasis (Applicant Benzing, Thomas )
• Chaperone-mediated redox control in organismal proteostasis regulation (Applicant Ulrich, Kathrin )
• Coordination Funds (Applicant Vilchez, David )
• Defining neurocircuits in cell non-autonomous control of liver proteostasis (Applicant Brüning, Jens Claus )
• Interorgan communication regulating stress exopher production in muscle cells (Applicants Deuerling, Ph.D., Elke ;  Gamerdinger, Ph.D., Martin )
• Mechanisms of organismal proteostasis regulation triggered by genotoxic stress (Applicant Schumacher, Björn )
• Regulation of neuronal proteostasis by the germline (Applicants Lee, Ph.D., Hyun Ju ;  Vilchez, David )
• Role of interorgan communication in balancing proteostasis and mitochondrial function (Applicant Trifunovic, Aleksandra )
• Role of sensory perception in cell non-autonomous proteostasis signaling (Applicant Hoppe, Ph.D., Thorsten )
• Z1 Platform for quantitative proteomics and data integration (Applicants Krüger, Marcus ;  Vilchez, David )

• Spokesperson: Professor Dr. David Vilchez