Projects Offered
Helle Ulrich Helle Ulrich_actin Helle Ulrich_4R Christof Niehrs_Bioinfo Christof Niehrs_4R Christof Niehrs_Ageing SvenDanck_4R Jan Padeken_4R Andreas Wachter_4R Roopesh Anand_4R Petra Beli_4R Brian Luke_4R Dorothee Dormann_4R Thomas Hofmann_4R Maria Felicia Basilicata_4R Katja Luck Sina Wittmann Sandra Schick Stamatis Papathanasiou Ari Waisman Wolfram Ruf Uwe Wolfrum Johannes Mayer_SkinDC Johannes Mayer_Exhaust Johannes Mayer_APCExploring the ubiquitin code in proteostasis and genome maintenance
1 PhD project offered in the IPP winter call Molecular Mechanisms in Genome Stability & Gene Regulation
Scientific Background
We study the regulatory mechanisms that contribute to ensuring the complete and accurate duplication of a cell’s genetic information in every cell cycle, especially in the face of DNA damage. We are particularly interested in 1) the emergence, repair and replicative processing of DNA damage on a genome-wide scale, and 2) the contributions of posttranslational protein modifiers of the ubiquitin family, such as ubiquitin and SUMO, to genome maintenance and other cellular processes.
PhD Project: Exploring the ubiquitin code in proteostasis and genome maintenance
The ubiquitin system plays a key role in determining the function and fate of proteins in virtually every biological pathway, including genome maintenance and gene expression. Most often, ubiquitin signalling is mediated by polyubiquitin chains attached to selected substrate proteins. Depending on the linkage between the individual ubiquitin moieties, such chains can adopt many distinct forms and - by means of linkage-selective downstream effectors - convey distinct biological effects. In this manner, the ubiquitin system is implicated in many human diseases such as cancer, neurodegeneration and inflammation. In our lab, we have developed tailor-made ubiquitylation enzymes that allow us to induce the polyubiquitylation of relevant cellular proteins in a controlled and linkage-selective manner. Here we will apply these tools to the investigation of ubiquitin signalling in selected biological contexts, including the processing of DNA polymerase-blocking lesions during DNA replication, the ubiquitin-dependent damage response pathway at DNA double-strand breaks, the contribution of ubiquitin to biological condensates via phase separation and the protection from pathological protein aggregates. The project will involve biochemical as well as cell and molecular biological approaches and aims to eluciate the relevance of ubiquitin signalling in cellular resilience mechanisms against ageing and disease.
If you are interested in this project, please select Ulrich (Ubi) as your group preference in the IPP application platform.
Publications relevant to this project
Renz C, Asimaki E, Meister C, Albanèse V, Petriukov K, Krapoth NC, Wegmann S, Wollscheid HP, Wong RP, Fulzele A, Chen JX, Léon S and Ulrich HD (2024) Ubiquiton-An inducible, linkage-specific polyubiquitylation tool. Mol Cell 84:386-400 Link
Yakoub G, Choi YS, Wong RP, Strauch T, Ann KJ, Cohen RE and Ulrich HD (2023) Avidity-based biosensors for ubiquitylated PCNA reveal choreography of DNA damage bypass. Sci Adv, 9:eadf3041 Link
Wegmann S, Meister C, Renz C, Yakoub G, Wollscheid HP, Takahashi DT, Mikicic I, Beli P and Ulrich HD (2022) Linkage reprogramming by tailor-made E3s reveals polyubiquitin chain requirements in DNA-damage bypass. Mol Cell, 82:1589-1602 Link
