Research
Centrioles, Centrosomes, Primary Cilia, Cell Biology, Biochemistry, Structural Biology
Interests
Centrioles are barrel-shaped cell organelles and are one of the largest protein assemblies found in animal cells. They form the core of centrosomes and thereby influence the organisation of the microtubule cytoskeleton in cells. If too many centrioles are made, extra centrosomes are assembled which can result in problems in cell division and diseases such as cancer. Centrioles also can use their distal appendages to dock to the cell membrane and template the outgrowth of hair-like cell projections called cilia and flagella. Cilia/flagella can move in a wave-like manner and thereby move fluid across the cell surface or propel cells, as observed in sperm cells. Other cilia types are immotile and act as sensory devices with which cells perceive their environment, e.g. smells, light or signalling molecules. Due to their key role in cilia formation, centriole defects can cause infertility and a class of diseases called ciliopathies.
Because of their size and complexity, centrioles are challenging to study experimentally. While many centriole components have been identified by genetic, cell biological and biochemical methods, it is poorly understood how exactly they come together, what precise role and mechanism of action these components have and how diseases result from their dysfunction. My lab addresses these questions using a wide variety of methods ranging from structural techniques such as X-ray crystallography and electron microscopy as well as biochemical and cell biological approaches.
Publications

Publications of specific relevance to the Centre for Molecular Cell Biology
2023
Proteomic profiling of centrosomes across multiple mammalian cell and tissue types by an affinity capture methodCarden S, Vitiello E, Rosa E Silva I, Holder J, Quarantotti V, Kishore K, Roamio Franklin VN, D'Santos C, Ochi T,
van Breugel M and Gergely F
Developmental Cell,
Elsevier vol. 58 (21), 2393-2410.e9.
17-10-20232022
Structural validation and assessment of AlphaFold2 predictions for centrosomal and centriolar proteins and their complexesvan Breugel M, Rosa e Silva I and Andreeva A
Communications Biology,
Springer Nature vol. 5 (1)
05-04-20222021
Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathiesRosa e Silva I, Binó L, Johnson CM, Rutherford TJ, Neuhaus D, Andreeva A, Čajánek L and
van Breugel M Structure,
Elsevier vol. 30 (1), 114-128.e9.
08-09-20212020
CCDC61/VFL3 Is a Paralog of SAS6 and Promotes Ciliary FunctionsOchi T, Quarantotti V, Lin H, Jullien J, Rosa e Silva I, Boselli F, Barnabas DD, Johnson CM, McLaughlin SH, Freund SMV, Blackford AN, Kimata Y, Goldstein RE, Jackson SP, Blundell TL, Dutcher SK, Gergely F and
van Breugel M Structure,
Elsevier vol. 28 (6), 674-689.e11.
05-05-2020
Direct interaction between CEP85 and STIL mediates PLK4-driven directed cell migration.Liu Y, Kim J, Philip R, Sridhar V, Chandrashekhar M, Moffat J,
van Breugel M and Pelletier L
Journal of Cell Science,
Company of Biologists vol. 133 (8)
23-04-20202018
Disease-Associated Mutations in CEP120 Destabilize the Protein and Impair CiliogenesisJoseph N, Al-Jassar C, Johnson CM, Andreeva A, Barnabas DD, Freund SMV, Gergely F and
van Breugel M Cell Reports,
Elsevier vol. 23 (9), 2805-2818.
01-05-2018
Direct binding of CEP85 to STIL ensures robust PLK4 activation and efficient centriole assemblyLiu Y, Gupta GD, Barnabas DD, Agircan FG, Mehmood S, Wu D, Coyaud E, Johnson CM, McLaughlin SH, Andreeva A, Freund SMV, Robinson CV, Cheung SWT, Raught B, Pelletier L and
van Breugel M Nature Communications,
Springer Nature vol. 9 (1)
30-04-20182016
The Ciliopathy-Associated Cep104 Protein Interacts with Tubulin and Nek1 KinaseAl-Jassar C, Andreeva A, Barnabas DD, McLaughlin SH, Johnson CM, Yu M and
van Breugel M Structure,
Elsevier vol. 25 (1), 146-156.
22-12-20162014
Structure of the SAS-6 cartwheel hub from Leishmania majorvan Breugel M, Wilcken R, McLaughlin SH, Rutherford TJ and Johnson CM
Elife,
Elife vol. 3
01-01-20142013
Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly.Cottee MA, Muschalik N, Wong YL, Johnson CM, Johnson S, Andreeva A, Oegema K, Lea SM, Raff JW and
van Breugel M Elife,
Elife Sciences Publications Ltd vol. 2, e01071-e01071.
17-09-20132011
Structures of SAS-6 Suggest Its Organization in Centriolesvan Breugel M, Hirono M, Andreeva A, Yanagisawa H-A, Yamaguchi S, Nakazawa Y, Morgner N, Petrovich M, Ebong I-O, Robinson CV, Johnson CM, Veprintsev D and Zuber B
Science,
American Association For The Advancement of Science (Aaas) vol. 331 (6021), 1196-1199.
27-01-2011