Centrioles are barrel-shaped structures that form two important cell organelles: centrosomes and cilia. These organelles play an important part in many aspects of cell organisation, and their dysfunction has been linked to a plethora of human pathologies including cancer and microcephaly (small brain). Our overarching goal is to understand how these organelles assemble and function at the molecular level, using a combination of biochemistry, genetics, live-cell imaging, computational/structural analysis and mathematical modelling.
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A pair of centrioles (middle schematic). In most non-dividing cells the centrioles organise cilia (left panel). In dividing cells, the centrioles duplicate and recruit 100s of proteins (collectively called the PCM) around themselves to form two centrosomes that form the poles of the mitotic spindle (right panel).
In Drosophila embryos, 100s of centrosomes (green) duplicate and form mitotic spindles (red) in tight synchrony. This allows us to extract high quality quantitative data detailing the behaviour of centrosomes and individual centrosome proteins.
Most cells in the human body are born with a pair of centrioles that can form two important cell organelles: cilia and centrosomes. These organelles play an important part in many aspects of cell organisation, including cell division, establishing and maintaining cell polarity, and positioning other organelles within the cell.
In dividing cells, the centrioles must duplicate once, and only once, during each round of cell division. Once duplicated, the centrioles have to be segregated equally between the two daughter cells. The centrioles do this by rapidly recruiting 100s of proteins (collectively termed pericentriolar material—PCM) around themselves to form centrosomes. The PCM contains many proteins that organise MTs, so the centrosomes form the two poles of the mitotic spindle, thus ensuring their accurate segregation into the two new daughter cells. Our overarching goal is to understand the molecular mechanisms that regulate centriole and centrosome assembly.
In the early Drosophila embryo, hundreds of centrioles and centrosomes synchronously assemble every few minutes as the embryos rapidly progress through repeated rounds of division. By combining live-cell imaging, computational analyses and mathematical modelling we have been generating quantitative descriptions of centrosome assembly with a precision that is not possible in other systems. We find that local oscillations in the levels of the key enzymes that initiate centriole and centrosome assembly are normally entrained by the CDK/Cyclin cell cycle oscillator to ensure that centrosomes assemble at the right time and place, and then grow to the right size. Our studies not only shed important light on centriole and centrosome assembly, but also potentially provide transformative new insights into how cells regulate and coordinate the biogenesis of their many organelles.
2022
Centriole growth is limited by the Cdk1/Cyclin-dependent phosphorylation of Ana2/STIL.
Steinacker, T.L., Wong, S-S., Novak, S.A., Saurya, S., Gartenmann, L., van Houtum, E.J.H., Sayers, J.R., Lagerholm, B.C. and Raff, J.W.
J Cell Biol. – 221(9): e202205058.
2022
Centrioles generate a local pulse of Polo/PLK1 activity to initiate mitotic centrosome assembly.
Wong, S-S., Wilmott, Z.M., Saurya, S., Alvarez-Rodrigo, I., Zhou, F.Y., Chau, K-Y., Goriely, A. and Raff, J.W.
EMBO J. – 41(11): e110891.
2020
An autonomous oscillation times and executes centriole biogenesis.
Aydogan, M.G., Steinacker, T.L., Mofatteh, M., Wilmott, Z., Zhou, F.Y., Gartenmann, L., Wainman, A., Saurya, S., Novak, Z.A., Wong, S.S., Goriely, A., Boemo, M.A. and Raff, J.W.
Cell – 181(7):1566-1581.e27.
2020
Drosophila Sas-6, Ana2 and Sas-4 self-organise into macromolecular structures that can be used to probe centriole and centrosome assembly.
Gartenmann, L., Vicente, C.C., Wainman, A., Novak, Z.A., Sieber, B., Richens, J.H. and Raff, J.W.
J Cell Sci. – 133(12): jcs244574.
2019
Evidence that a positive feedback loop drives centrosome maturation in fly embryos.
Alavarez Rodrigo, I., Steinacker, T.L., Saurya, S., Conduit, P.T., Baumbach, J., Novak, Z.A., Aydogan, M.G., Wainman, A. and Raff, J.W.
eLife – 8: e50130.
2018
A homeostatic clock sets daughter centriole size in flies.
Aydogan, M.G., Wainman, A., Saurya, S., Steinacker, T.L., Caballe, A., Novak, Z.A., Baumbach, J., Muschalik, N. and Raff, J.W.
J Cell Biol. – 217(4): 1233-1248.
2017
Structural basis for mitotic centrosome assembly in flies.
Feng, Z., Caballe, A., Wainman, A., Johnson, S., Haensele, A.F.M., Cottee, M.A., Conduit, P.T., Lea, S.M. and Raff, J.W.
Cell – 169(6): 1078-1089
Protein phosphorylation-mediated control of centriole growth
August 2022
Published in the Journal of Cell Biology, work by the Raff lab uncovers a key new mechanism mediated by protein phosphorylation that regulates centriole growth and duplication during the cell cycle. The cell cycle is a highly regulated cellular process required for tissue development and homeostasis, whose dysregulation is associated with cancer. Centrioles are microtubule-based...
Pulse to the beat: centrosome assembly requires a pulse of Polo kinase activity
June 2022
In a story published in the EMBO Journal, Wong, Wilmott et al. shed light on the mechanism of Polo action in the assembly of the centrosome. Cell division is an essential function of cells, and appropriate partitioning of DNA and other cellular materials is critical for the daughter cells’ functioning and survival. In animals, this process...
Susan Lea and Jordan Raff elected Fellows of the Royal Society
May 2022
Many congratulations to Susan and Jordan for this prestigious honour, recognising their contributions to structural and centrosome biology, respectively.
Jordan Raff receives Excellence in Science Award
April 2022
Awarded by the Biochemical Society, this honour recognises his leading role in the field of centriole and centrosome biology.