Ruprecht-Karls-Universit├Ąt Heidelberg
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Schiebel0119 - Scientist (f/m) / PhD position
Project no:

Project leader:

Project supervisor:
Schiebel, Elmar
Application deadline:
31. Jul 2019
Start of PhD project:
1. Sep 2019

Project description:

Maintenance of the nuclear pore complex in aged cells and their plasticity in cancer
The nuclear pore complex (NPC) is a large cylindrical structure of over 30 different proteins named nucleoporins (NUPs) that is embedded in the nuclear envelope. It facilitates the essential process of nuclear-cytoplasmic transport of RNA molecules and proteins.

NPCs assemble in the intact nuclear envelope by an inside-out mechanism. How this process works, is modulated during aging and changed in cancer cells is largely unknown and will be studied in this project. We have developed a fast and highly efficient CRISPR approach for gene tagging. With this in hand, we will tag endogenous NUPs with fluorophores such as NeonGreen and degron tags and study their behaviour, function and biogenesis in different cell lines and under various growth conditions.
1 Ruthnick, 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).

2 Ruthnick, D. & Schiebel, E. Duplication and Nuclear Envelope Insertion of the Yeast Microtubule Organizing Centre, the Spindle Pole Body. Cells 7, doi:10.3390/cells7050042 (2018).

3 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).

4 Vlijm, R. et al. STED nanoscopy of the centrosome linker reveals a CEP68-organized, periodic rootletin network anchored to a C-Nap1 ring at centrioles. Proc Natl Acad Sci U S A 115, E2246-E2253, doi:10.1073/pnas.1716840115 (2018).

5 Zhang, W. et al. Brr6 and Brl1 locate to nuclear pore complex assembly sites to promote their biogenesis. J Cell Biol 217, 877-894, doi:10.1083/jcb.201706024 (2018).

Methods that will be used:
The PhD student will use biochemical approaches, conventional light and super resolution microscopy (STED; SIM) and electron microscopy for the analysis of the NPCs. CRISPR technology will be used for genomic tagging of human NUPs.
Cooperation partners:
Personal qualifications:
Highly motivated PhD students with a background in biochemistry, cell biology or molecular biology should apply.