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PhD Position: Interphase nuclear pore complex biogenesis
Category:
Phd

Description:

The nuclear pore complex (NPC) is a large cylindrical structure with multiple copies of over 30 different proteins named nucleoporins. 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. Nucleoporins become deposited from within the nucleus to the inner nuclear membrane, deform this membrane and eventually the inner and outer nuclear membranes fuse. Recently, we discovered that Brr6 and Brl1, two conserved integral membrane proteins of the NE, play a role in NE fusion during NPC biogenesis. Furthermore, the yeast microtubule organizing centre, the spindle pole body (SPB), probably needs an NPC for its insertion into the NE. However, it is not understood if this NPC is delivering insertion factors or if the SPB uses the NPC to actively insert through the pore of the NPC into the NE. This NPC might be sacrificed during the SPB insertion process or could be release from the SPB sideways into the NE.

In this project we will study NPC biogenesis and how the SPB is using an NPC for its NE insertion. The NPC biogenesis project will be carried out in yeast and human cells as models. The PhD student will use biochemical approaches, conventional light microscopy and super resolution microscopy (STED; live cell analysis with SIM), electron microscopy and CRISPR/Cas9 technology, genomic tagging of human nucleoporins; auxin degron for protein depletion.

Relevant publications:

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 CNap1 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).

Your profile: 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 Heidelberg Biosciences International Graduate School (HBIGS) (http://www.hbigs.uni-heidelberg.de/).

We offer: The PhD position is funded for 3 years with starting date based on mutual agreement (as soon as possible). The remuneration is based on TV-L. Please notice that the received application documents will not be returned.

Application process and contact: Interested? Applications should be sent via Email to Prof. Elmar Schiebel (schiebel.elmar [ aT ] zmbh.uni-heidelberg.de) and contain the following documents (in English): CV, motivation letter, two references. We are looking forward to your application!