The cytoskeleton, fibres of actin, microtubules and intermediate filaments spatially organize cells. Defects in the microtubule network contribute to cancer and can cause brain defects (e.g. microcephaly) due to brain stem cell death and ciliopathies because of the malfunction of cilia in various organs. Here we will analyse how microtubules are spatially assembled and regulated in cultured cells and in tissues. In focus of the research are the microcephaly proteins pericentrin and CDK5RAP2 that interact with and regulate the gamma-tubulin ring complex. You will use state of the art techniques to address the function of pericentrin and CDK5RAP2 such as cell engineering with CRISPR/Cas9, super resolution microscopy (SIM, PALM, STED), light sheet microscopy and electron microscopy.
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 (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 (E13/60%) is funded for 3 years.
1 Chinen, T. et al. The gamma-tubulin-specific inhibitor gatastatin reveals temporal requirements of microtubule nucleation during the cell cycle. Nat Commun 6, 8722, doi:10.1038/ncomms9722 (2015).
2 Lin, T. C. et al. Cell-cycle dependent phosphorylation of yeast pericentrin regulates gamma-TuSC-mediated microtubule nucleation. Elife 3, e02208, doi:10.7554/eLife.02208 (2014).
3 Gombos, L. et al. GTP regulates the microtubule nucleation activity of gamma-tubulin. Nat Cell Biol 15, 1317-1327, doi:ncb2863 [pii]10.1038/ncb2863 (2013).
4 Erlemann, S. et al. An extended γ-tubulin ring functions as a stable platform in microtubule nucleation. J Cell Biol 197, 59-74, doi:jcb.201111123 [pii]10.1083/jcb.201111123 (2012).
Lin, T. C., Neuner, A. & Schiebel, E. Targeting of gamma-tubulin complexes to microtubule organizing centers: conservation and divergence. Trends Cell Biol 25, 296-307, doi:10.1016/j.tcb.2014.12.002 (2015).