Projects Offered
Roopesh Anand Petra Beli Dorothee Dormann Thomas Hofmann René Ketting Carlotta Martelli Christof Niehrs_Ageing Christof Niehrs_Bioinfo Christof Niehrs_4R Sandra Schick Helle Ulrich Andreas Wachter Johannes Mayer_DCMem Johannes Mayer_DCSkin Wolfram Ruf Tim Sparwasser Ari WaismanDeciphering the Ubiquitin Code
1 PhD project offered in the IPP summer call Molecular Mechanisms in Genome Stability & Gene Regulation
Scientific Background
Our lab studies regulatory mechanisms at the interface of proteostasis and genome stability. We are particularly interested in the diverse signalling functions of the posttranslational modifier ubiquitin, which is best known for its role in protein degradation, but also contributes to a variety of other cellular pathways, including DNA repair and replication.
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, not only in protein quality control, but also in processes such as genome maintenance, gene expression, and signal transduction. 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. Via this so-called “ubiquitin code”, the ubiquitin system protects us from diseases such as cancer, premature ageing, inflammation and neurodegeneration. In our lab, we have developed a proteomics-based method, named “LinkageID”, to systematically isolate cellular factors associated with particular linkages. By applying this technique in mammalian cell culture and budding yeast, we aim to identify novel ubiquitin targets, relevant enzymes as well as downstream effectors of linkage-specific polyubiquitylation. The PhD student involved in this project will perform LinkageID under defined stress conditions and/or for selected linkages to investigate the impact of polyubiquitylation in relevant biological contexts, for example in ubiquitin-dependent DNA damage signalling and repair, in the response to DNA replication stress, or in newly emerging areas resulting from the screen. Downsteam functional analyses will then involve biochemical as well as cell and molecular biological approaches. In this manner, the project aims to eluciate the relevance of linkage-specific ubiquitin signalling in cellular resilience mechanisms against ageing and disease.
If you are interested in this project, please select Ulrich 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
