Centre for Molecular Biology (ZMBH)
University of Heidelberg
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.
The PhD student will use biochemical approaches, conventional light and super resolution microscopy (STED; SIM)and electron microscopyfor the analysis of the NPCs. CRISPR technology will be used for genomic tagging of human NUPs.
Relevant recent publications:
1 Ruthnick, D. & Schiebel, E. Duplication of the Yeast Spindle Pole Body Once per Cell Cycle. Mol Cell Biol36, 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. Cells7, 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 Biol209, 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 A115, 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 Biol217, 877-894, doi:10.1083/jcb.201706024 (2018).
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 willbe a member of the Heidelberg Biosciences International Graduate School (HBIGS) (http://www.hbigs.uni-heidelberg.de/).The PhD position is funded for 3 years.
Please send applications (CV, motivation letter, two references, bachelor and master transcripts) toE. Schiebel (email@example.com).