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Archiv-Übersicht     Angebot Nr. 12854

Angebotsdatum: 28. Mai 2018
Art der Stelle: Doktorarbeit
Fachgebiet: Biologie > Molekularbiologie
Titel des Themas: Protein quality control and cell adaptation to stress

Institut: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Dr. rer. nat. Sebastian Schuck
Im Neuenheimer Feld 282
69120 Heidelberg
Tel.:    Fax.:
Bundesland: Baden-Württemberg
Homepage: http://www.zmbh.uni-heidelberg.de/Schuck
E-Mail Kontakt: mail

Beschreibung: This project is an opportunity to explore SHRED, a novel pathway regulating protein degradation during stress.

Cells eliminate damaged proteins as part of protein quality control. This ability is essential for cell adaptation to stress, and failure to destroy the right proteins at the right time leads to disease. For example, inefficient protein degradation during aging causes disorders such as Alzheimer’s. Similarly, cancer cells chronically accumulate misfolded proteins and only survive by degrading them. Therefore, activating or inhibiting protein degradation may help combat many diseases. For this, a key step is to understand the mechanisms by which cells regulate protein degradation.

We have recently discovered SHRED (stress-induced homeostatically regulated protein degradation), a novel regulatory pathway in yeast that specifies the targets of protein degradation (Szoradi et al., Molecular Cell, in press). Stress induces the synthesis of the protein Roq1, which is proteolytically cleaved and reprograms the ubiquitin ligase Ubr1 for accelerated degradation of misfolded proteins. The aims of this project are to elucidate the molecular mechanism of SHRED through biochemical in vitro reconstitution, identify the physiological roles of SHRED in yeast, and determine if SHRED exists in mammals.

If you are interested, please visit our website for more information (http://www.zmbh.uni-heidelberg.de/Schuck) and contact s.schuck@zmbh.uni-heidelberg.de.
Methoden: The in vitro reconstitution of SHRED will involve the purification of recombinant proteins, biochemical ubiquitination assays and cryo-electron microscopy. The analysis of SHRED functions will involve yeast as a model organism, genetic screening approaches, and biochemical as well as flow cytometric protein degradation assays. The search for mammalian SHRED will involve mammalian tissue culture, protein affinity purification, and a bit of luck.
Anfangsdatum: 28. Mai 2018
Geschätzte Dauer: 3 - 4 Jahre
Bezahlung: E13 60%
Papers: Szoradi, T, Schaeff K, … and Schuck S. SHRED is a regulatory cascade that reprograms Ubr1 substrate specificity for enhanced protein quality control during stress. Molecular Cell, 2018.
Sonstiges: Are you passionate about understanding life’s fascinating complexity at the molecular level? If so, our young lab in a lively, international and collaborative research environment may be the right place for you. A strong background in biochemistry or molecular cell biology is essential for this project. Also, you should be comfortable working in an English-speaking environment.