Ruprecht-Karls-Universität Heidelberg

Open Positions in the Schiebel Lab

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PhD position

Role of Human Ubiquitin-like ISG15 in Cancer Development”

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 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. We will test the impact of ISGylation on cell migration using the wound healing assay and random cell migration.
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).

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.

 

June 2017

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PhD position

"Microtubule biology

Microtubules are highly dynamic polymers that assemble at centrosomes, chromatin and pre-exiting microtubules. They are essential for cell organization including Golgi positioning, intracellular transport, cell migration and chromosome segregation in mitosis and meiosis. Shortly after assembly, microtubules become severed and capped at their minus end by stabilizing factors such as CAMSAP/Patronin. Here we will analyse how microtubules are spatially assembled in cells, how they become released from nucleation sites and captured by the Golgi and appendages of centrosomes.

The PhD student will use biochemical approaches, super resolution microscopy (STED), electron microscopy (negative stain and cryo-EM), CRISPR/Cas9 technology and live cell imaging to study microtubules and associated proteins.
Highly motivated PhD students with a background in biochemistry, 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 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).

Relevant publications:

1          Lin, T. C et al. MOZART1 and gamma-tubulin complex receptors are both required to turn gamma-TuSC into an active microtubule nucleation template. J. Cell Biol 215, 823-840. pii:jcb.201606092 (2017).
2          Chinen, T. et al. The gamma-tubulin-specific inhibitor gatastatin reveals temporal requirements of microtubule nucleation during the cell cycle. Nat Commun 6, 8722, doi:10.1038/ncomms9722 (2015).           
3          Lin, T. C. et al. Cell-cycle dependent phosphorylation of yeast pericentrin regulates gamma-TuSC-mediated microtubule nucleation. Elife 3, e02208, doi:10.7554/eLife.02208 (2014).
4          Gombos, L. et al. GTP regulates the microtubule nucleation activity of gamma-tubulin. Nat Cell Biol 15, 1317-1327, doi:ncb2863 [pii]10.1038/ncb2863 (2013).
5          Erlemann, S. et al. An extended γ-tubulin ring functions as a stable platform in microtubule nucleation. J Cell Biol 197, 59-74, doi:jcb.201111123 [pii]10.1083/jcb.201111123 (2012).

Reviews:

Lin, T. C., Neuner, A. & Schiebel, E. Targeting of gamma-tubulin complexes to microtubule organizing centers: conservation and divergence. Trends Cell Biol 25, 296-307, doi:10.1016/j.tcb.2014.12.002 (2015).

 

 

June 2017

 


 

 

 

 


 

 

 

 

 

 

 

 

 

 

 







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