Supervisor: Jordan Raff

Eukaryotic cells are packed full of many different structurally complex organelles that perform a myriad of functions. Organelle number and size appear to be tightly regulated. In proliferating cells, for example, the amount of each organelle doubles prior to cell division, but the mechanisms that ensure cells make the right amount of each organelle at the right time and at the right place are poorly understood. Centrioles are an excellent model for studying this problem, as almost every cell in the human body is born with just a single pair of centrioles. These tiny structures organise two crucial organelles—cilia and centrosomes—that have vital roles in many aspects of cellular organisation (e.g. cell division, cell polarity, cell signalling). The dysfunction of these organelles has been linked to many different human diseases, including cancer, obesity, retinal degeneration and microcephaly/dwarfism, but the mechanisms linking these pathologies to organelle dysfunction are poorly understood. These structures are composed of multiple copies of hundreds of different types of protein yet, in rapidly dividing Drosophila embryos, they can assemble in just a few minutes. We want to understand how cells build these complicated machines with such precision.

We individually knocked-out most of the ~13,000 genes in fly cells and found that, surprisingly, only ~15-20 are essential for centriole and centrosome assembly. Similar studies in worms identified a similar set of genes, indicating that the centrioles and centrosome assembly pathways are highly conserved. In this project you will use advanced microscopy to study fluorescently tagged versions of normal and mutated versions of these key assembly proteins in living fly embryos. In these embryos we can observe 100s of centrioles and centrosomes proceeding through multiple rounds of very rapid assembly at an unprecedented spatial and temporal resolution. We have developed sophisticated tools to extract quantitative information from these large imaging datasets, allowing us to formulate and test models and so define the principles that ensure that centrioles and centrosomes assemble at the right time, in the right place, and grow to the right size. Excitingly, these studies have recently allowed us to reconstitute centriole and centrosome assembly on the surface of synthetic beads injected in to embryos. These studies are revealing the principles that govern organelle assembly, providing a blueprint that might one day allow us to design and construct our own complex biological nanomachines.

Publications:

1. Wong, S-S. et al., (2025). Centrioles generate two scaffolds with distinct biophysical properties to build mitotic centrosomes. Sci. Adv., Doi: 10.1126/sciadv.adq9549
2. Wong, S-S et al. (2024). Regulation of centrosome size by the cell-cycle oscillator in Drosophila embryos. EMBO J., Doi: 10.1038/s44318-023-00022-z
3. Aydogan, et al. (2020). An autonomous oscillation times and executes centriole biogenesis. Cell, Doi: 10.1016/j.cell.2020.05.018.
4. Conduit P.T., et al. (2015). Centrosome function and assembly in animal cells. Nat. Rev. Cell and Mol. Biol. Doi: 10.1038/nrm4062.