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Decipher the CDC14 puzzle
Category:
Phd

Description:
CDC14 encodes a highly conserved phosphatase that is essential for mitotic exit in the model organism budding yeast. Human cells have two CDC14 paralogues, named hCDC14A and hCDC14B. Very surprisingly, the double knockout of hCDC14A and hCDC14B in human cells does not affect viability and cell cycle progression raising the question of the function of these human phosphatases. Recently we could show that hCDC14A is associated with the actin cytoskeleton where it regulates cell adhesion and cell migration. In addition, genomic knockout of hCDC14A in human colon cancer HCT116 cells makes cells more invasive than HCT116 control cells. This fits with the observation that downregulation of hCDC14A expression in cancer is associated with poor survival of patients. In this project we will identify substrates of hCDC14A and hCDC14B by comparing the phospho-proteome profiles of hCDC14A/B knockouts with wild type cells by SILAC and mass spectrometry analysis. In addition, we will identify proximity interactors of hCDC14A/B using the newly developed BioID approach. hCDC14A substrates will be analysed for their role in hCDC14A regulated cell migration and adhesion (cell engineering with CRISPR/Cas9 to obtain phospho-mimetic and -inhibitor mutants, mutant analysis for cell migration and adhesion defects; soft agar assays for anchorage independent cell growth). Moreover, since hCDC14B associates with the nucleolus, we expect that this phosphatase has different functions and substrates than hCDC14A.

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.

Relevant publications:

1          Chen, N. P., Uddin, B., Voit, R. & Schiebel, E. Human phosphatase CDC14A is recruited to the cell leading edge to regulate cell migration and adhesion. Proc Natl Acad Sci U S A 113, 990-995, doi:10.1073/pnas.1515605113 (2016).

2          Mocciaro, A. et al. Vertebrate cells genetically deficient for Cdc14A or Cdc14B retain DNA damage checkpoint proficiency but are impaired in DNA repair. J Cell Biol 189, 631-639, doi:jcb.200910057 [pii]10.1083/jcb.200910057 (2010).

3          Agircan, F. G., Hata, S., Nussbaum-Krammer, C., Atorino, E. & Schiebel, E. Proximity mapping of human separase by the BioID approach. Biochem Biophys Res Commun, doi:10.1016/j.bbrc.2016.08.002 (2016).

4          Pereira, G. & Schiebel, E. Separase regulates INCENP-Aurora B anaphase spindle function through Cdc14. Science 302, 2120-2124, doi:10.1126/science.1091936 (2003).

Reviews:

Mocciaro, A. & Schiebel, E. Cdc14: a highly conserved family of phosphatases with non-conserved functions? J Cell Sci 123, 2867-2876, (2010).

 

Contact details:

E. Schiebel

schiebel.elmar [ aT ] zmbh.uni-heidelberg.de