Ruprecht-Karls-Universität Heidelberg
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Schiebel0120 - Scientist (f/m) / PhD position
Project no:
Schiebel0120

Project leader:

Project supervisor:
Schiebel, Elmar
Application deadline:
31. Jan 2020
Start of PhD project:
1. Mar 2020

Project description:

Title:
Microtubules – building them at the right time, at the right place
Summary:
Microtubules are highly dynamic polymers with essential functions in chromosome segregation in mitosis and meiosis, intracellular organization, cell motility and neurogenesis. Microtubules are targets for drugs that are used in cancer therapy (Paclitaxel and Vinca alkaloids). Microtubule malfunction is associated with cancer, infertility and neurological diseases.

Using gamma-tubulin complexes, cells have developed mechanisms for the assembly of microtubules from tubulin subunits. We just have resolved the high resolution cryo-EM structure of the large vertebrate gamma-tubulin ring complex (γ-TuRC) composed of over 30 subunits (published in Nature 2019). Unexpectedly, we identified actin as a component of the γ-TuRC. The activity of the γ-TuRC is modulated in time and space by accessory factors, for example microtubule polymerases and activators such as the microcephaly protein CDK5RAP2.

In this project we aim to understand the role of actin in the γ-TuRC, when and where regulatory co-factors play a role, how they impact the structure of the γ-TuRC and how the activity of these regulators is changed in cancer and adapted in specific cell types, for example neurons.

Please send applications (CV, motivation letter, two references, bachelor and master transcripts) to E. Schiebel (schiebel.elmar@zmbh.uni-heidelberg.de).

References:
Liu P, Zupa E, Neuner A, Böhler A, Loerke J, Flemming D, Ruppert T, Rudack T, Peter C, Spahn C, Gruss OJ, Pfeffer S, Schiebel E (2019). Insights into the assembly and activation of the microtubule nucleator γ-TuRC. Nature. doi: 10.1038/s41586-019-1896-6.

Gunzelmann J, Ruthnick D, Lin TC, Zhang W, Neuner A, Jakle U, Schiebel E (2018) The microtubule polymerase Stu2 promotes oligomerization of the gamma-TuSC for cytoplasmic microtubule nucleation. Elife 7: e39932

Lin TC, Neuner A, Flemming D, Liu P, Chinen T, Jakle U, Arkowitz R, Schiebel E (2016) 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

Lin TC, Neuner A, Schiebel E (2015) Targeting of gamma-tubulin complexes to microtubule organizing centers: conservation and divergence. Trends Cell Biol 25: 296-307

Lin TC, Neuner A, Schlosser YT, Scharf AN, Weber L, Schiebel E (2014) Cell-cycle dependent phosphorylation of yeast pericentrin regulates gamma-TuSC-mediated microtubule nucleation. Elife 3: e02208

Gombos L, Neuner A, Berynskyy M, Fava LL, Wade RC, Sachse C, Schiebel E (2013) GTP regulates the microtubule nucleation activity of gamma-tubulin. Nat Cell Biol 15: 1317-27

Erlemann S, Neuner A, Gombos L, Gibeaux R, Antony C, Schiebel E (2012) An extended γ-tubulin ring functions as a stable platform in microtubule nucleation. J Cell Biol 197: 59-74

Knop M, Schiebel E (1998) Receptors determine the cellular localization of a γ-tubulin complex and thereby the site of microtubule formation. EMBO J 17: 3952-3967

Methods that will be used:
The PhD student will be using a broad range of techniques such as cryo-electron microscopy, CRISPR/Cas9 technology for genomic knockins and knockouts and live cell imaging to study microtubule assembly.
Cooperation partners:
Personal qualifications:
The highly motivated PhD student should have a background in biochemistry or cell biology.
Keywords: