Projects Offered
Petra Beli Dorothee Dormann Ulrich Hohmann René Ketting Edward Lemke Stamatis Papathanasiou Helle Ulrich Eva Wolf Johannes Mayer_Ageing Johannes Mayer_Dynamics Daniel Sasca 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 the maintenance of mitochondrial homeostasis.
PhD Project: Contributions of the ubiquitin system to mitochondrial quality control
The ubiquitin system plays a key role in determining the function and fate of proteins in virtually every biological pathway, including protein quality control, 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. We have recently 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 plan to identify novel ubiquitin targets, relevant enzymes as well as downstream effectors of linkage-specific polyubiquitylation.
This project aims at elucidating the importance of ubiquitin linkage in controlling the import of proteins into mitochondria. Defects in the cellular components guiding this process disrupt mitochondrial function and are associated with several diseases. The ubiquitin system is known to ensure the maintenance of the import system and remove dysfunctional channels, but the relevant substrates, enzymes and regulatory factors are still poorly understood. The PhD student involved in this project will perform LinkageID under conditions where mitochondrial protein import is impaired to investigate the impact of polyubiquitin chain linkage and identify the factors involved. Downstream functional analyses will then involve biochemical as well as cell and molecular biological approaches. In this manner, the project aims to elucidate the relevance of linkage-specific ubiquitin signalling in an important cellular resilience mechanism 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 these projects
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
