Centriole and centrosome assembly

Centrioles and centrosomes have many important roles in eukaryotic cells, and their dysfunction has been linked to various human diseases, ranging from cancer to dwarfism. Our overarching goal is to understand how these organelles assemble and function at the molecular level. We have developed sophisticated imaging and computational methods to quantify the dynamic behaviour of fluorescently-tagged proteins in the early, syncytial Drosophila embryo, where hundreds of centrioles and centrosomes synchronously assemble every few minutes. This has allowed us to quantify the behaviour of individual proteins during the assembly process with a precision that is currently not possible in any other system. We are deriving mathematical models of the assembly processes and testing them by combining the powerful genetics available in flies with our precise measurements that allow us to detect even subtle changes in assembly kinetics. Our recent studies have led to several surprising and important discoveries—most notably that centriole assembly is timed and executed by a centriole-associated oscillator. Our work will ultimately generate a complete molecular and mathematical description of centriole and centrosome assembly in flies. We expect that the principles we discover will apply to centriole, centrosome and organelle assembly in other systems.