Ruprecht-Karls-Universität Heidelberg

Open Positions in the Schiebel Lab

 

PhD position: “Role of Human Ubiquitin-like ISG15 in Cell Regulation and Cancer Development”
Centre for Molecular Biology (ZMBH)
Heidelberg University

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.
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.

 


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PhD position: “Centrosome duplication
Centre for Molecular Biology (ZMBH)
Heidelberg University

The centrosomes is the main microtubule organizing centre of human cells. As DNA centrosomes duplicate once per cell cycle. Malfunction of centrosome duplication is a hallmark of cancer cells and recent data suggest that centrosome overamplificaiton contributes to cell transformation. In addition, lack of centrosomes or to many centrosomes causes chromosome missegregation and p53 activation leading to cell cycle arrest in G1.

In this project we will study cell cycle dependent centrosome duplication and steps leading to centrosome maturation in G2 and mitosis. The PhD student will use biochemical approaches, super resolution microscopy (STED), electron microscopy, CRISPR/Cas9 technology and live cell imaging to study centrosome duplication in untransformed and cancer cells.
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:

1-51       Mardin, B. R., Agircan, F. G., Lange, C. & Schiebel, E. Plk1 Controls the Nek2A-PP1gamma Antagonism in Centrosome Disjunction. Curr Biol 21, 1145-1151, doi:S0960-9822(11)00605-1 [pii]
10.1016/j.cub.2011.05.047 (2011).
2          Mardin, B. R. et al. EGF-induced centrosome separation promotes mitotic progression and cell survival. Dev Cell 25, 229-240, doi:S1534-5807(13)00161-5 [pii]
10.1016/j.devcel.2013.03.012 (2013).
3          Mardin, B. R. et al. Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat Cell Biol 12, 1166-1176, doi:ncb2120 [pii]
10.1038/ncb2120 (2010).
4          Mardin, B. R. & Schiebel, E. Breaking the ties that bind: New advances in centrosome biology. J Cell Biol 197, 11-18, doi:jcb.201108006 [pii]
10.1083/jcb.201108006 (2012).
5          Rüthnick, D. & Schiebel, E. Duplication of the yeast spindle pole body once per cell cycle. Mol Cell Biol 36, 1324-1331, doi:10.1128/MCB.00048-16 (2016).

 

 

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PhD position: “Nuclear pore complex biogenesis
Centre for Molecular Biology (ZMBH)
Heidelberg University

The nuclear pore complex (NPC) is a large cylindrical structure with multiple copies of over 30 different proteins named nucleoporins (NUPs). The NPC is embedded in the nuclear envelope (NE) at fusion sites of the inner and outer nuclear membrane where it facilitates nuclear-cytoplasmic transport of RNA and proteins. NPCs assemble in the intact nuclear envelope (interphase human cells or yeast cells with a closed mitosis) by an inside-out mechanism. NUPs become deposited from within the nucleus to the inner nuclear membrane, deform this membrane and eventually the inner and outer nuclear membranes fuse. We recently have identified with Brr6 and Brl1 two conserved integral membrane proteins that may play a role in nuclear membrane fusion during NPC biogenesis.

In this project we will study NPC biogenesis using budding yeast and human cells as model systems. The PhD student will use biochemical approaches (Brr6 and Brl1 reconstitution into liposomes), super resolution microscopy (SIM and STED), electron microscopy, CRISPR/Cas9 technology and live cell imaging to study NPC assembly.
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 recent publications:

1          Zhang, W. et al. Brr6 1 and Brl1 locate to nuclear pore complex assembly sites to promote their biogenesis. J Cell Biol in press (2018).
2          Ruthnick, D. et al. Characterization of spindle pole body duplication reveals a regulatory role for nuclear pore complexes. J Cell Biol 216, 2425-2442, doi:10.1083/jcb.201612129 (2017).
3          Rüthnick, D. & Schiebel, E. Duplication of the yeast spindle pole body once per cell cycle. Mol Cell Biol 36, 1324-1331, doi:10.1128/MCB.00048-16 (2016).
4          Seybold, C. et al. Kar1 binding to Sfi1 C-terminal regions anchors the SPB bridge to the nuclear envelope. J Cell Biol 209, 843-861, doi:10.1083/jcb.201412050 (2015).

 

 

 

 

 


 

 

 

 

 

 

 

 

 

 

 







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