Mark van Breugel

Structure and assembly mechanisms of centrioles
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Centrioles are one of the largest protein assemblies in cells. They constitute the core of centrosomes and are strictly required to template cilia and flagella. Numerous human diseases such as infertility, ciliopathies and cancer are associated with the malfunction of centriolar components.

Despite their importance, the molecular architecture of centriole as well as their assembly, duplication and effector mechanisms are currently poorly understood. In the past we showed how a critical assembly intermediate of centrioles is organised and how this contributes to the establishment of centriole symmetry. The challenge ahead is to extend this assembly and also to structurally understand the architecture of entire centrioles.

The PhD candidate will combine biochemical and structural techniques, such as X-ray crystallography and cryo-EM to address these questions. Furthermore, the resulting models will be tested in vivo with cell biological and genetic methods. The PhD project provides an excellent opportunity for a multidisciplinary training and has the potential to uncover groundbreaking insights into a fascinating and essential cell organelle.


References:

van Breugel, M., Hirono, M., Andreeva, A., Yanagisawa, H.A., Yamaguchi, S., Nakazawa, Y., Morgner, N., Petrovich, M., Ebong, I.O., Robinson, C.V., Johnson, C.M., Veprintsev, D., Zuber, B. (2011)
Structures of SAS-6 suggest its organization in centrioles.
Science, 331(6021):1196-9.

Cottee, M.A., Muschalik, N., Wong, Y.L., Johnson, C.M., Johnson, S., Andreeva, A., Oegema, K., Lea, S.M., Raff J.W., van Breugel, M.  (2013).
Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly.
eLife2:e01071

van Breugel, M., Wilcken, R., McLaughlin, S.H., Rutherford, T.J., Johnson, C.M. (2014).
Structure of the SAS-6 cartwheel hub from Leishmania major.
Elife 3:e01812