Ruprecht-Karls-Universität Heidelberg
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Schiebel0118 - Scientist (f/m) / PhD position
Project no:
Schiebel0118

Project leader:

Project supervisor:
Schiebel, Elmar
Application deadline:
15. Jun 2018
Start of PhD project:
1. Aug 2018

Project description:

Title:
Role of Human Ubiquitin-like ISG15 in Cell Regulation and Cancer Development
Summary:
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.

Please send applications to E. Schiebel (schiebel.elmar@zmbh.uni-heidelberg.de).
References:
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.
Methods that will be used:
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.
Cooperation partners:
Personal qualifications:
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. The PhD position is funded for 3 years.
Keywords: