The DFG (German Research Foundation) 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), 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”, says the speaker of the new research training group, Prof. Brian Luke, who is also a Professor at JGU and an Adjunct Director at IMB. The DFG will support the project with approximately €6.8 million during the first 5 years, with an additional €1.49 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 explains. 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”, says Brian. He points out that R-loops, which occur in animals, plants and bacteria as well as humans, play a significant role in important processes such as DNA repair, telomere elongation and gene regulation.
An RTG 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 JGU’s 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”, says IMB’s Executive Director Prof. 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 characterise 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”, says 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 programme for PhD students.
Further details
Further information can be found at: www.dfg.de/service/presse/pressemitteilungen/2023/pressemitteilung_nr_12/index.html.
Brian Luke is an Adjunct Director at the Institute of Molecular Biology (IMB) and a Professor at Johannes Gutenberg University Mainz. Further information about research in the Luke lab can be found at www.imb.de/luke.
René Ketting is the Executive Director of the Institute of Molecular Biology (IMB). Further information about research in the Ketting lab can be found at www.imb.de/ketting.
About the Institute of Molecular Biology gGmbH
The Institute of Molecular Biology gGmbH (IMB) is a centre 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 institute is a prime example of successful collaboration between a private foundation and government: The Boehringer Ingelheim Foundation has committed 154 million euros to be disbursed from 2009 until 2027 to cover the operating costs of research at IMB. The State of Rhineland-Palatinate has provided approximately 50 million euros for the construction of a state-of-the-art building and is giving a further 52 million in core funding from 2020 until 2027. For more information about IMB, please visit: www.imb.de.
About the Centre for Healthy Ageing
The Centre for Healthy Ageing (CHA) is a virtual research centre launched in 2021 that brings together scientists in basic and clinical research from across Mainz that focus on ageing and age-related diseases. These findings should be used to promote healthy ageing and to find treatments that could prevent or cure age-related disease. For more information, please visit: www.cha-mainz.de.
About Johannes Gutenberg University Mainz
Johannes Gutenberg University Mainz (JGU) is a globally recognized research-driven university with around 31,000 students from over 120 nations. Its core research areas are in particle and hadron physics, the materials sciences, and translational medicine. JGU's success in Germany's Excellence Strategy program has confirmed its academic excellence: In 2018, the research network PRISMA+ (Precision Physics, Fundamental Interactions and Structure of Matter) was recognized as a Cluster of Excellence – building on its forerunner, PRISMA. Moreover, excellent placings in national and international rankings as well as numerous honors and awards demonstrate the research and teaching quality of Mainz-based researchers and academics. Further information at www.uni-mainz.de/eng
Boehringer Ingelheim Foundation
The Boehringer Ingelheim Foundation is an independent, non-profit organization that is committed to the promotion of the medical, biological, chemical, and pharmaceutical sciences. It was established in 1977 by Hubertus Liebrecht (1931–1991), a member of the shareholder family of the Boehringer Ingelheim company. Through its Perspectives Programme Plus 3 and its Exploration Grants, the Foundation supports independent junior group leaders. It also endows the international Heinrich Wieland Prize, as well as awards for up-and-coming scientists in Germany. In addition, the Foundation funds institutional projects in Germany, such as the Institute of Molecular Biology (IMB), the department of life sciences at the University of Mainz, and the European Molecular Biology Laboratory (EMBL) in Heidelberg. www.bistiftung.de
Press contact for further information
Dr Ralf Dahm, Director of Scientific Management
Institute of Molecular Biology gGmbH (IMB), Ackermannweg 4, 55128 Mainz, Germany
Phone: +49 (0) 6131 39 21455, Email: press@imb.de