Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) Mainz is offering talented scientists the chance to work on cutting edge research projects within the open call on “Molecular Mechanisms in Genome Stability & Gene Regulation”. As an IPP PhD student, you will join a community of exceptional scientists working on diverse topics ranging from how organisms age or how our DNA is repaired, to how epigenetics regulates cellular identity or neural memory. The research group of Petra Beli offers the following PhD project: R-loops are secondary DNA structures consisting of an RNA-DNA hybrid and a single stranded DNA that can form behind the elongating RNA polymerase II during transcription. R-loops play regulatory roles during transcription initiation and termination. However, the accumulation of R-loops in the genome results in replication stress, DNA double-strand breaks and genomic instability. A number of proteins including ribonucleases, helicases and translocases have been shown to regulate R-loop levels in cells. In recent years, R-loops have been recognized as a major cell-intrinsic source of genomic instability, and dysregulation of R-loop processing is associated with cancer and neurodegenerative diseases. We have developed an unbiased mass spectrometry-based proteomics approach to identify proteins that regulate R-loops in human cells and discovered a role for the tumor suppressor DDX41 in R-loop resolution. PhD Project: Mechanisms opposing R-loop-associated DNA double strand breaks The PhD project will be part of the DFG-funded SFB 1361 “Regulation od DNA Repair and Genome Stability”. The PhD student will profit from collaboration and networking with other research groups, all focusing on understanding the molecular mechanisms modulating genome maintenance pathways in the cell. The Beli group has expertise in quantitative proteomics approaches in analyzing protein interactions and regulation on chromatin. The project will focus on understanding the regulation of Ribonuclease H1, which digests the RNA moiety in the R-loops and plays a central role in R-loop resolution. We will analyze how the activity of this enzyme is directed to pathological compared to regulatory R-loops to maintain genome stability. In this regard, we will focus on phosphorylation and ubiquitylation as well as the compartmentalization of pathological R-loops in biological condensates. Furthermore, we will analyze systems-wide responses to R-loop-associated genomic instability, also exploring the interplay between R-loop accumulation and inflammatory response. We will take advantage of unique tools that were previously developed in our lab to map R-loops and associated proteins with proximity-based proteomics and high-content microscopy. If you are interested in this project, please select Beli as your group preference in the IPP application platform. Are you an ambitious scientist looking to push the boundaries of research while interacting with colleagues from multiple disciplines and cultures? Then joining the IPP is your opportunity to give your scientific career a flying start! All you need is: Master or equivalent Interactive personality & good command of English 2 letters of reference We offer Exciting, interdisciplinary projects in a lively international environment, with English as our working language Advanced training in scientific techniques and professional skills Access to our state-of-the-art Core Facilities and their technical expertise Fully funded positions with financing until the completion of your thesis A lively community of more than 200 PhD students from 44 different countries For more details on the projects offered and how to apply via the online form.