CRC 1678

Collaborative Research Center 1678

Systems-level consequences of fidelity changes in mRNA and protein biosynthesis

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.

Project Leaders

Petra Beli

Institute of Molecular Biology, Johannes Gutenberg University, Mainz

Andreas Beyer

Andreas Beyer (Speaker)

Institute for Genetics, CECAD, University of Cologne

Débora Broch Trentini Schmidt

Center for Molecular Medicine Cologne, University of Cologne

Niels Gehring

Niels Gehring

Institute for Genetics, University of Cologne

Robert Hänsel-Hertsch

Robert Hänsel-Hertsch

Center for Molecular Medicine Cologne, University of Cologne

Thorsten Hoppe

Institute for Genetics, CECAD, University of Cologne

Hupertz

Ina Huppertz

Max Planck Institute for Biology of Ageing, Cologne

Zoya Ignatova

Zoya Ignatova

Institute for Biochemistry and Molecular Biology, University of Hamburg

Marcus Krüger

Institute for Genetics, CECAD, University of Cologne

Andreas Mayer

Max Planck Institute for Molecular Genetics, Berlin

Roman Ulrich Müller

Department II of Internal Medicine, University of Cologne

Panier

Stephanie Panier

Max Planck Institute for Biology of Ageing, Cologne

Argyris Papantonis

Institute of Pathology, University Medical Center Göttingen

Paola Picotti

Institute of Molecular Systems Biology, ETH Zürich

Jan Riemer

Institute for Biochemistry, University of Cologne

Björn Schumacher

Björn Schumacher

Institute for Genome Stability and Aging, CECAD, University of Cologne

Achim Tresch

Achim Tresch

Institute of Medical Statistics and Computational Biology, University of Cologne

Kathrin Ulrich

Institute for Biochemistry, University of Cologne

David Vilchez

David Vilchez

CECAD, University of Cologne

Weith

Matthias Weith

Institute for Biochemistry, University of Cologne

Research Area A

mRNA Biosynthesis

A01

Transcript quality effects of RNAPII speed variation

A02

Maintaining gene expression fidelity in response to DNA- and RNA-protein crosslinks

A03

The role of chromatin structure regulation in the susceptibility to transcription-blocking lesions

A04

Consequences of age-related G-quadruplex formation for the fidelity of mammalian transcription

A05

Regulation of splicing fidelity in response to DNA double-strand breaks

A06

Regulation of alternative polyadenylation by RNA-binding proteins in senescence

A07

Speed vs. fidelity: The role of nuclear RNA export under cellular stress

A08

Impact of nonsense-mediated mRNA decay on gene expression fidelity

Research Area B

Protein Biosynthesis

B01

Clearance of defective mRNA by-products by the ribosome-associated quality control pathway in stress and disease

B02

Coordination of endoplasmic reticulum-associated fidelity machines

B03

Stress-dependent regulation of organellar proteome plasticity by dynamic selection of different translation initiation sites

B04

Chronic stress-associated alterations of translation fidelity

B05

Predicting the impact of biosynthetic fidelity on protein folding

B06

Defining the interplay between RNA and protein toxicity in C9orf72-related amyotrophic lateral sclerosis

B07

Protein targeting and safeguarding upon oxidative unfolding stress

B08

Metabolic signaling as a safeguard of translational fidelity

Central Projects C

Central Projects

CP01

Administration, communication, dissemination

CP02

Quantitative Proteomics

INF

Information Infrastructure Project: Scientific data management and data analytics

IRTG

Integrated Research Training Group