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Archiv-Übersicht     Angebot Nr. 13557

Angebotsdatum: 12. August 2019
Art der Stelle: Doktorarbeit
Fachgebiet: Biologie > Zellbiologie
Titel des Themas: The Fbxw7 tumor suppessor and its key role in oncogenesis

Institut: German Cancer Research Center, DKFZ
Adresse:
Prof. Ingrid Hoffmann
Im Neuenheimer Feld 242
69120 Heidelberg
Tel.:    Fax.:
Bundesland: Baden-Württemberg
Homepage: http://www.dkfz.de/en/f045/index.php
E-Mail Kontakt: mail

Beschreibung: The important role of ubiquitin in basic cellular processes is exemplified by award of the 2004 Nobel Prize in Chemistry for ubiquitin research. In the past two decades, our understanding of ubiquitin molecules has evolved tremendously. Particularly, increased knowledge of their role in protein modification and cancer has led to the development of several targeted therapeutics, some of which are currently in clinical trials. Because the ubiquitin system and the proteasome are involved in cell growth, cell death and DNA damage repair, cancer cells like viruses often hijack the ubiquitination process to mediate survival through evasion of apoptosis, a key hallmark of cancer.
The goal of the PhD project is to unravel the pathway that regulates the protein levels of the ubiquitin ligase component Fbxw7. The SCF-Fbxw7 complex has previously been characterized as an important tumor suppressor as it is mutated in a variety of human cancers. Moreover, the proteasomal degradation of key cellular oncoproteins, as for example Cyclin E, c-Myc, Notch and c-Jun, has been shown to be mediated by the SCF-Fbxw7 complex. Although numerous substrates of the complex are already well-established, the upstream regulation of the SCF-Fbxw7 activity and its protein levels is only poorly understood. Therefore, the characterization of a novel pathway that regulates the protein levels of Fbxw7 is of high interest and has the potential to considerably impact the cancer and ubiquitin research fields.
We offer working in an enthusiastic international environment, detailed initial skill adaptation training regarding methods, regular lab meetings and literature seminars, lab retreats, the possibility to attend national and international conferences.
Methoden:
Anfangsdatum: 1. Oktober 2019
Geschätzte Dauer: 3 Jahre
Bezahlung: E13, 65%
Papers: Cizmecioglu, O, Krause, A., Bahtz, R., Malek, N. and Hoffmann, I. (2012) Phosphorylation of Fbxw7/hCdc4 regulated by Plk2 promotes cyclin E stabilization, J Cell Sci. 125, 981-992.
Kratz, AS., Richter, K., Schlosser, Y., Schmitt, M., Shumilov, A., Delecluse HJ and Hoffmann, I. (2016) Fbxo28 regulates topoisomerase IIalpha-dependent DNA decatenation, Cell Cycle, 15, 3419-3431.
Richter, KT, Kschonsak, YT, Vodicska, B. and Hoffmann I. (2019) FBXO45-MYCBP2 regulates mitotic cell fate by targeting FBXW7 for degradation
Cell Death and Differentiation in press
Sonstiges: We are looking for a highly motivated PhD student with a background in cell biology and/or biochemistry. Master's or diploma degree in biology, biochemistry or closely related fields, basic knowledge in biochemical and cell biological techniques.
Please send your CV, transcript of records from high school, bachelor and master studies and the names and e-mail addresses of two referees.

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