GRK 2859:  R-loop Regulation in Robustness and Resilience

• Subject Area: Basic Research in Biology and Medicine
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 491145305

R-loops are three-stranded nucleic acid structures made up of an RNA-DNA hybrid and a displaced strand of DNA. They are formed when the nascent RNA threads back to the DNA double helix and base-pairs with the template strand of DNA. R-loops were initially thought to be toxic by-products of transcription, but it has recently been shown that they are dynamically regulated and play important physiological roles through the regulation of many chromosomal transactions, including: DNA repair, transcription regulation and chromatin establishment. The precision of these transactions is critical to ensure that cells display resilience and robustness in the face of environmental change and stress. Within the context of this RTG we will explore the functionality and regulation of R-loops with respect to many molecular processes, such as: telomere maintenance, DNA repair, alternative splicing and transcription termination. In addition, we will develop molecular tools and methods to further characterize R-loop location throughout the genome and try to better understand the difference between scheduled (regulatory) R-loops and unscheduled (harmful) R-loops. We will try to answer fundamental and exciting questions in terms of R-loop biology, for example: Why do some R-loops promote transcription, while others prevent it? Why do some R-loops promote DNA repair whereas others lead to DNA damage? How do R-loops regulate replicative senescence following telomere loss? Can R-loops affect gene silencing in the siRNA pathway? In this manner, all students within the 4R RTG will have R-loops as a common focal point, but many other molecular processes will be investigated. Hence, our program ensures that the students will be exposed to a broad range of biology and biochemistry, but the strong emphasis on R-loops will provide a common ground among all projects. Together, this will provide an optimal basis for collaboration and discussion. In addition, students will be part of a well-established graduate school with training opportunities in scientific practice as well as providing them exposure to industry and scientific communication. In summary, the 4R program will provide students with the opportunity to explore scientific questions on a very timely subject and at the same time offer them training in the skills required to be successful following their time as a PhD student.

• DFG Programme: Research Training Groups
• Applicant Institution: Johannes Gutenberg-Universität Mainz
• Participating Institution: Institut für Molekulare Biologie gGmbH
• Spokesperson: Professor Dr. Brian Luke, Ph.D.
• Participating Researchers: Dr. Maria Felicia Basilicata; Professor Dr. Peter Baumann, Ph.D.; Professorin Dr. Petra Beli; Professor Dr. Sven Danckwardt; Professorin Dr. Dorothee Dormann; Professor Dr. Thomas G. Hofmann, Ph.D.; Dr. Claudia Isabelle Keller Valsecchi, Ph.D.; Professor Dr. René Ketting, Ph.D.; Dr. Julian König, Ph.D.; Professor Dr. Christof Niehrs, Ph.D.; Dr. Jan Padeken; Professorin Dr. Helle Ulrich, Ph.D.; Professor Dr. Andreas Wachter, Ph.D.