SFB 1565:  Molecular mechanisms and interplay of gene expression processes

• Subject Area: Biology ; Medicine
• Term: since 2023
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 469281184

Gene expression sculpts the cellular RNA and protein composition, and determines the identity of cells. An emerging concept is that gene expression is not a linear pathway but rather a highly dynamic network of interconnected processes. Genome organization and transcription, RNA processing and modification, RNA-protein complex assembly, translation and quality control are interconnected processes and many cross-regulation events occur even between non-consecutive steps of gene expression, and even between steps taking place in different cellular compartments. This paradigm shift is of central importance for understanding the regulation of gene expression in various cellular conditions and its dysregulation in diseases. Key mechanistic and regulatory aspects of gene expression still remain unexplored, and knowledge on the extent and mechanisms of cross-regulation between different processes is still in its infancy. With this Collaborative Research Centre (CRC), we aim to resolve structures and functions of key events in the pathway that have remained enigmatic, but also decipher how different processes are coordinated in space and time, and in different gene expression systems. Structural views of gene expression machineries and structure-informed functional analyses will pioneer new mechanistic insights and systematic mapping of DNA-/RNA-protein interactions will reveal pivotal interconnections. Establishing an integrated view of the molecular principles and dynamics of gene expression and the networks of cross-regulation will shape our understanding of this important cellular pathway and also of its modulation in different cellular conditions. Understanding regulatory mechanisms in different gene expression systems will allow principles of regulation and interconnections to be dissected. Tackling these ambitious goals requires the concerted efforts of leading experts in each aspect of gene expression and can therefore only be approached in the context of a CRC. This research initiative holds the promise to provide an unprecedented view of gene expression as a defining network of interconnected cellular processes and thereby also to pave the way for the elucidation of the molecular basis of diseases.

• DFG Programme: Collaborative Research Centres

Current projects

• P02 - The role of the Mediator complex in the regulation of enhancer-promoter interactions and gene expression (Project Head Oudelaar, A. Marieke )
• P03 - Multifunctional chromatin factors in control of gene expression and nuclear architecture (Project Head Papantonis, Argyris )
• P04 - Dissecting protein-RNA and -DNA interactions in cells through crosslinking/mass spectrometry analyses (Project Head Urlaub, Henning )
• P05 - Coordination of genome maintenance and gene expression processes through multifunctional molecular machineries (Project Head Wahl, Markus C. )
• P06 - Regulation of nucleoplasmic steps in gene expression processes by the multifunctional RNA helicase DHX15 and its cofactor network (Project Head Bohnsack, Markus T. )
• P07 - High-resolution structural and mechanistic analyses of spliceosomal complexes and other RNPs by cryo-EM (Project Head Stark, Holger )
• P08 - Influence of perturbed ribosome assembly on transcription and pre-mRNA splicing in crosstalk with the oncogenes MDM2 and MDM4 (Project Head Dobbelstein, Matthias )
• P09 - Structural and mechanistic analysis of nucleocytoplasmic shuttling of RNAs (Project Head Ficner, Ralf )
• P10 - mRNA guard protein-mediated rRNA and snoRNA quality control (Project Head Krebber, Heike )
• P11 - Endoribonuclease-mediated regulation of the balance between RNA degradation and transcription (Project Head Stülke, Jörg )
• P12 - Post-translational regulation of ribonucleases and their roles in processing and decay of diverse RNAs during cellular stress (Project Head Bohnsack, Ph.D., Katherine )
• P13 - Mechanisms and interconnections of transcription and ribosome biogenesis in mitochondria (Project Head Hillen, Hauke )
• P14 - Interconnections of the mitochondrial translation machinery (Project Head Rehling, Peter )
• P15 - Speed, accuracy and quality control of translation (Project Heads Rodnina, Marina V. ;  Wohlgemuth, Ingo )
• P16 - Advanced Single Molecule Fluorescence Spectroscopy to analyze RNA and protein dynamics (Project Head Enderlein, Jörg )
• P17 - Dissecting the structural and functional crosstalk of the protein synthesis and ISG15-modification machineries (Project Head Lorenz, Sonja Gisela )
• P18 - The influence of RNA modifications on tRNA-derived small RNA biogenesis, molecular interactions and their diverse functions in gene expression regulation (Project Heads Bohnsack, Markus T. ;  Höbartner, Claudia )
• P19 - The interplay of mitochondrial ribosomes and the quality control machinery during ribosome rescue (Project Head Richter-Dennerlein, Ricarda )
• Z01 - Central Task of the Collaborative Research Center (Project Head Bohnsack, Markus T. )
• Z02 - Mass spectrometry Service (Project Head Lenz, Christof )

• Applicant Institution: Georg-August-Universität Göttingen
• Participating Institution: Max-Planck-Institut für Multidisziplinäre Naturwissenschaften
• Participating University: Freie Universität Berlin; Julius-Maximilians-Universität Würzburg
• Spokesperson: Professor Dr. Markus T. Bohnsack