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Archiv-Übersicht     Angebot Nr. 12687

Angebotsdatum: 12. Februar 2018
Art der Stelle: Doktorarbeit
Fachgebiet: Biologie > Molekularbiologie
Titel des Themas: PhD position "Role of human ubiquitin-like ISG15 in cell regulation and cancer development"

Institut: University of Heidelberg, Center for Molecular Biology (ZMBH)
Prof. Elmar Schiebel
Im Neuenheimer Feld 282
69120 Heidelberg
Tel.:    Fax.:
Bundesland: Baden-Württemberg
E-Mail Kontakt: mail

Beschreibung: The Interferon-Stimulated Gene 15 product, ISG15, modifies proteins in a similar manner to ubiquitin. ISG15 appears to play important roles in various biological and cellular functions including innate immunity, cell adaptation to actin defects and DNA damage. In addition, overexpression of ISG15 has been shown to contribute to metastatic abilities of certain breast cancer cell lines suggesting that ISG15 promotes tumor formation. However, relative to ubiquitin, substrates of ISG15 and the molecular consequences of this conjugation are still poorly understood. Recently, we have identified the human Ras GTPase-activating-like protein IQGAP1, a scaffold protein that interacts with RAC1 and CDC42, as an ISG15 substrate. ISGylation of IQGAP1 has an impact on the interaction of RAC1 and CDC42 with IQGAP1 and the activity of these GTPases.
In this project we will identify substrates of ISG15 by affinity purification and mass spectrometry-based approaches and identify the proteins that recognize ISGylated proteins. We will study the consequences of substrate ISGylation for normal cell growth and in malignancy. ISG15 substrates will be analysed using CRISPR/Cas9 knockin and knockout strategies.
Anfangsdatum: 15. März 2018
Geschätzte Dauer: 3 years
Bezahlung: TV-L E13/60%
Papers: Relevant publications from our laboratory:

Cerikan, B., R. Shaheen, G.P. Colo, C. Gläßer, S. Hata, K.-P. Knobeloch, F.S. Alkuraya, R. Fässler, and E. Schiebel. (2016). Cell intrinsic adaptation arising from chronic ablation of a key Rho GTPase regulator. Dev. Cell, 39:28-43.

Cerikan B. and E. Schiebel. (2017). Mechanism of cell-intrinsic adaptation to Adams-Oliver Syndrome gene DOCK6 disruption highlights ubiquitin-like modifier ISG15 as a regulator of RHO GTPases. Small GTPases, 23:1-8.

Chen, N.-P., B. Uddin, R. Hardt, W. Ding, M. Panic, I. Lucibello, P. Kammerer, T. Ruppert and E. Schiebel. (2017). Human phosphatase CDC14A regulates actin organization through dephosphorylation of epithelial protein lost in neoplasm. Proc. Natl. Acad. Sci. U S A, 114:5201-5206.

Chen, N.-P., B. Uddin, R. Voit, and E. Schiebel. (2016). Human phosphatase CDC14A is recruited to the cell leading edge to regulate cell migration and adhesion. Proc. Natl. Acad. Sci. USA, 113:990-995.
Sonstiges: Highly motivated PhD students with a background in cell biology or molecular biology should apply. Successful candidates will be part of an international team of PhD students and postdocs that works at the forefront of scientific research (http://www.cell.com/developmental-cell/meet-the-author/berati-cerikan). The PhD student will be a member of the Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology (http://www.hbigs.uni-heidelberg.de/). The PhD position is funded for 3 years.
Please send applications to E. Schiebel (schiebel.elmar@zmbh.uni-heidelberg.de).