German Research Foundation approves new Research Training Group on the biology of R-loops at Mainz University

New Research Training Group "R-loop Regulation in Robustness and Resilience" dedicates itself to highly topical field of research

8 May 2023

The German Research Foundation (DFG) has approved a new Research Training Group (RTG) on "R-loop Regulation in Robustness and Resilience" (4R). This research initiative was applied for by Johannes Gutenberg University Mainz (JGU) in close cooperation with the Institute of Molecular Biology (IMB) in Mainz and focuses on R-loops, which are a highly topical subject in the field of genome biology research.

The new RTG will investigate "R-loops", which are a specific type of RNA-DNA hybrid with both positive and negative effects in cells. From autumn 2023, 12 PhD students will begin their research projects in this field as part of 4R. "It's a rapidly evolving research field, with many successful and ground-breaking findings over the past five years. We are delighted to be able to start intensive research on the subject with this Research Training Group", said the speaker of the new RTG, Professor Brian Luke, who is a Professor at JGU and an Adjunct Director at IMB. The DFG will support the project with approximately EUR 6.8 million during the first five years, with an additional EUR 2 million for overheads.

The 4R RTG will investigate open questions on the benefits and risks of R-Loops

RNA-DNA hybrids form when RNA and single-stranded DNA, which are structurally similar molecules, bind to each other. One particularly interesting type of RNA-DNA hybrid is R-loops, which contain three strands: two DNA and one RNA, with one of the DNA strands being displaced to form a loop. "Previously, R-loops were considered to be a byproduct of RNA biosynthesis: RNA was thought to get caught on a DNA strand, causing breaks in the DNA and damaging the chromosomes", Brian explained. This could, in turn, promote inflammatory diseases and cancer as well as accelerate ageing. More recent discoveries indicate that it is not the formation of the R-loops per se that causes these problems, but rather their faulty removal, which leaves them "in the wrong place at the wrong time, because they were not removed in time", said Brian. He points out that R-loops, which occur in animals, plants, bacteria as well as humans, play a significant role in important processes such as DNA repair, telomere elongation, and gene regulation.

Research Training Group based in Mainz with interdisciplinary participants

The 4R RTG integrates 12 research groups, allowing the PhD students to explore a diverse range of biochemical processes in addition to the specific focus on the regulation of R-loops. This includes groups from JGU's Faculty of Biology and IMB as well as two groups from the Mainz University Medical Center to encourage the development of translational applications. "This is the first RTG with a direct focus on the biology of R-loops", said IMB's Executive Director Professor René Ketting, who is also deputy speaker of the RTG. "R-loops have recently become a focal point of intense interest in genome biology, and we hope that this research will help us to understand their mechanisms of action in the cell more precisely."

To achieve this, the 4R RTG will develop molecular tools and methods to characterize the function of R-loops throughout the genome and decipher the difference between planned and unplanned R-loops. "There is a distinct lack of knowledge when it comes to the question of why R-loops can sometimes be beneficial and sometimes do harm", said Brian. "It appears that the regulation of these structures is crucial but complicated. We have many highly topical and relevant research questions ahead of us."

4R is the second collaborative RTG between JGU and IMB

4R is the second RTG jointly organised by JGU's Faculty of Biology and IMB that has been successfully funded by the DFG. The first RTG on "Gene Regulation in Evolution: From Molecular to Extended Phenotypes" (GenEvo) was approved in 2019 and aims to improve our understanding of the evolution of complex and multilayered gene regulatory systems through a structured, high-quality research and training program for PhD students.

About the Institute of Molecular Biology gGmbH

The Institute of Molecular Biology gGmbH (IMB) is a center of excellence in the life sciences that was established in 2011 on the campus of Johannes Gutenberg University Mainz (JGU). Research at IMB focuses on the cutting-edge fields of epigenetics, genome stability, ageing, and RNA biology. The IMB is a prime example of successful collaboration between a private foundation and government: The Boehringer Ingelheim Foundation has committed EUR 154 million to be disbursed from 2009 until 2027 to cover the operating costs of research at IMB. The State of Rhineland-Palatinate has provided approximately EUR 50 million for the construction of a state-of-the-art building and is giving a further EUR 52 million in core funding from 2020 until 2027.