University of Cologne
Collaborative Research Center 1678
Systems-level consequences of fidelity changes in mRNA and protein biosynthesis
CRC 1678 investigates how age and stress-driven declines in the accuracy of mRNA and protein production affect cellular and organismal health. By taking an integrated, systems-level approach, we aim to uncover how these fidelity changes drive disease and aging.
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About CRC 1678
Exploring the Fidelity of mRNA and Protein Biosynthesis in Aging and Stress
The fidelity of cellular processes that control and execute the biosynthesis of mRNA and proteins declines with age and when challenged by external stressors. This decline results in the production of physiologically unfavorable quantities (amounts) and poor quality (e.g. erroneous sequence, altered folding, or localization) of mRNA and proteins. We and others have shown that this fidelity decline contributes to disease mechanisms and to age-associated physiological changes. Whereas some of the processes involved in either mRNA or protein biosynthesis have been studied at great detail, an integrated, comprehensive view of the systemic consequences of fidelity decline is lacking. This Collaborative Research Centre (CRC) aims to address how fidelity changes in mRNA and protein biosynthesis collectively impact cellular and organismal functions
Collaborative Research Center 1678
Key features
Integrated analysis of mRNA and protein biosynthesis with a systems perspective
This CRC emphasizes interdisciplinary collaboration by examining cellular processes in mRNA and protein biosynthesis and homeostasis. Projects synergize through shared research on biosynthetic processes, data, technologies, and biological models. Instead of isolating processes, this CRC utilizes a systems approach to explore the crosstalk between cellular fidelity mechanisms.
Innovative technologies
Our CRC project leaders have developed innovative technologies that advance the study of RNA and protein metabolism fidelity. Key methods include genome-wide G4 structure detection, factory-seq for nascent transcripts, , limited proteolysis mass spectrometry (LiP-MS) for protein folding, RNA-DNA proximity proteomics (RDProx) for R-loop-associated proteins, protein-RNA interactions at nucleotide resolution (iCLIP), NET-seq for Pol-II mapping, and in vivo reporter assays in C. elegans.
Computational data integration
To achieve a systems-level understanding, Our CRC integrates systems biology, machine learning, and computational biology to achieve insights beyond isolated projects. CRC project leaders are computational biology experts with extensive experience in developing new methods, including analyzing chromatin structural data, interpreting ribosome profiling, and quantifying regulatory pathway activity. We created the INF Project, a platform for integrating large-scale molecular datasets. Expert curators ensure proper annotation for reusability and optimal integration. Data integration will be facilitated by common cellular models and harmonized experimental procedures.
Projects
Research Area A: mRNA Biosynthesis
Research Area A investigates the mechanisms that safeguard mRNA integrity, ensuring accurate gene expression and cellular adaptation to stress over time. It focuses on key processes in mRNA biosynthesis, including transcription, splicing, and nuclear RNA export. Researchers examine how factors such as RNA polymerase II (RNAPII) speed, chromatin structure, and age-related G-quadruplex formation affect transcription fidelity. Additionally, this area explores how cells preserve splicing accuracy in response to DNA damage and regulate alternative polyadenylation and RNA export under stress conditions.
Research Area B: Protein Biosynthesis
Research Area B explores how cells maintain protein biosynthesis fidelity and how its disruption affects health, stress resilience, and neurodegenerative diseases. It focuses on quality control mechanisms governing translation, protein folding, and localization. Researchers investigate how cells detect and eliminate defective mRNA, regulate translation under stress, and ensure proper protein folding and targeting. Special attention is given to the impact of chronic stress on translational accuracy, the role of metabolic signaling in safeguarding protein synthesis, and the interplay between RNA and protein toxicity in disorders such as C9orf72-related ALS.
Central Projects C
They ensure strategic coordination, foster communication and outreach, and actively promote gender equality. In addition, they offer cutting-edge proteomics technologies to map dynamic protein changes and support CRC-wide data interpretation. The Information Infrastructure Project (INF) provides essential expertise in bioinformatics, data management, and customized analysis pipelines to unlock insights from complex ‘omics’ data. Finally, the Integrated Research Training Group (IRTG) empowers early-career scientists with hands-on training, interdisciplinary exchange, and diverse career development pathways.