Ubiquitin in nuclear protein quality control

1 PhD project offered in the IPP summer call 2020

Scientific Background

Within the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 860517, the Beli lab at the Institute of Molecular Biology (IMB) in Mainz is offering a PhD position for an Early Stage Researcher (ESR).
The UBIMOTIF consortium includes 13 research groups and 6 partners from 10 European countries and is a joint training and research program with focus on identification, characterization and exploitation of short linear motifs in the ubiquitin system. Visit www.ubimotif.ku.dk for more information.

Description of the network
The ubiquitin system is a major promising source for novel therapeutic approaches but its potential has not been fully exploited due to our limited understanding of ways to target the ubiquitin system. Ubiquitin ligases and deubiquitinating enzymes (DUBs) are enzymes that actively add or remove ubiquitin from proteins to regulate cell physiology. How these enzymes selectively recognize their substrates is largely unknown but an emerging theme is that a globular domain in the enzyme binds a short linear interaction motif (SLiM) in the substrate. The UBIMOTIF consortium aims to exploit novel technological advances to identify, characterize and exploit SLiMs on substrates that mediate interactions with ubiquitin ligases and DUBs.
The Beli laboratory develops and employs quantitative mass spectrometry-based proteomics approaches to characterize ubiquitin signaling in nuclear protein quality control and DNA damage response.

PhD project (ESR3 project):

The family of HECT-type ubiquitin ligases has been implicated in human disorders including neurodegeneration and cancer. In this project, we will define substrate specificity principles for nuclear HECT-type ubiquitin ligases and characterize the functional role of selected ubiquitin ligase – substrate relations in proteome dynamics and quality control.

Publications relevant to the projects

Hildebrandt A, Brüggemann M, Rücklé C, Boerner S, Heidelberger J B, Busch A, Hänel H, Voigt A, Möckel M M, Ebersberger S, Scholz A, Dold A, Schmid T, Ebersberger I, Roignant J Y, Zarnack K, König J, Beli P (2019) The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation. Genome Biol., 20(1):216.

Heidelberger J B, Voigt A, Borisova M E, Petrosino G, Ruf S, Wagner S A, Beli P (2018) Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function.EMBO Rep. Apr;19(4).

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