PhD position: SUMOylation and Ubiquitylation in cell signaling
Category:
Phd

Description:

Project no: Melchior0218

Project supervisor: Melchior, Frauke

Application deadline: 31. Dec 2018

Start of PhD project: 1. Jan 2019

 

Summary:

Research in our group centers around posttranslational modification with small ubiquitin-related proteins of the SUMO family. Like ubiquitin, these proteins can be covalently and reversibly linked to other proteins. Reversible protein SUMOylation is an essential process that regulates hundreds of individual proteins in numerous pathways, including cell cycle control, transcription, DNA damage response and oxidative stress. SUMOylation of specific proteins is subject to regulation by other modifications; conversely, SUMO is known to regulate enzymes involved in other posttranslational modifications including phosphorylation, acetylation and ubiquitylation.

 

We have a PhD student project available in a project that connects SUMOylation and Ubiquitylation in signal transduction: we recently discovered a complex that contains both a Ubiquitin E3 ligase and a SUMO enzyme, and which contributes to NFkB signaling. This raises intriguing possibilities, e.g., that SUMOylation regulates the Ubiquitin E3 ligase or that SUMOylation of a substrate precedes its ubiquitylation. Major aims in this project will be to understand at the molecular and cellular level how and why these enzymes interact and to identify substrates of the ubiquitin E3 ligase.

 

References:

Review:

  • Flotho, F. and Melchior, F. (2013) SUMOylation - a regulatory protein modification in health and disease. Annu. Rev. Biochem. 82, 357-385.

Webinar:

  • https://www.youtube.com/watch?v=X2AxZu05U4U

Selected original publications:

  • Stankovic-Valentin, N., Drzewicka, K., König, C., Schiebel, E. and Melchior, F. (2016) Redox-regulation of SUMO enzymes is required for ATM activity and survival in oxidative stress. EMBO J. 35, 1312-1329.

  • Werner, A., Disanza, A., Reifenberger N, Habeck G., Becker, J., Calabrese, M., Urlaub, H., Lorenz, H., Schulman, B., Scita, G. and Melchior, F. (2013) SCFFbxw5 mediates transient degradation of actin remodeler Eps8 to allow proper mitotic progression. Nat. Cell Biol. 15, 179 -188.

  • Meulmeester, E., Kunze, M., Hsiaoh, H.H., Urlaub, H., Melchior, F. (2008) Mechanism and consequences of paralog specific sumoylation of USP25. Mol. Cell 30, 610-619.

 

Methods that will be used:

The projects will require a wide range of biochemical, molecular biological and cell biological methods including, e.g., recombinant protein expression and purification, in vitro and cell-based analyses of SUMOylation and ubiquitinylation, ubiquitylation on proteinarrays, proteomics, immunofluorescence, reporter assays, CRISPR/Cas9 and others.

 

Personal qualifications:

We are seeking highly motivated PhD students with a strong background in protein biochemistry and cell biology or molecular biology and a broad interest in fundamental aspects of cellular functions. The successful candidates will be part of a very collaborative team of Postdocs, PhD students, Master students and technicians. A special incentive will be membership in a collaborative research networks, the SFB 1036 “Cellular Surveillance and damage response” http://www.zmbh.uni-heidelberg.de/sfb1036/