Exploring the role of a novel basal-body protein in construction of cilia in Drosophila

Cilia are highly structured eukaryotic organelles that perform a variety of motile and sensory functions in development and physiology. In humans, defects in cilium formation (i.e. ciliogenesis) result in so-called ciliopathies – multifaceted inherited diseases with features that reflect the range of processes that require cilia. Such features include sensory defects (e.g. photoreceptor degeneration, anosmia), kidney and lung problems (e.g. polycystic kidneys), and developmental defects (e.g. polydactyly). Studies of model organisms, including Drosophila, have greatly advanced our knowledge of the proteins required for ciliogenesis. The study of cilia in Drosophila is facilitated by that fact cilia are confined to just two cell types – sensory neurons and spermatozoa. Therefore, mutation of genes encoding ciliogenesis proteins characteristically result in sensory defects and male infertility. In addition to facilitating the discovery of new ciliogenesis genes, Drosophila provides an excellent model for the in vivo analysis of function of ciliogenesis proteins.

Recently we discovered a new gene involved in ciliogenesis. This gene, dilatory, encodes a coiled-coil protein that is located at the base of neuronal cilia. Here the protein localises to a structure known as the basal body, a modified centrosome that plays several key roles in constructing the cilium. When mutated, the flies are uncoordinated and males are infertile. Cilia are shortened, suggesting a defect in transport of components into the cilium (this work is currently in press). The regulation of transport into the cilium is a crucial but poorly characterised role of the basal body. In this project, the student will investigate dilatory’s function in detail to determine the molecular mechanism of its action and to find interacting partner proteins in the basal body. Avenues of research may include: localisation of Dilatory protein by immuno-electron microscopy; assaying ciliary transport in dilatory mutants (by live imaging; a genetic modifier screen to identify new protein partners of Dilatory protein.

The dilatory gene is conserved in humans, making it a candidate gene for ciliopathies. Anything learnt will be directly relevant to human physiology, development and disease. There may also be the possibility of exploring dilatory function in zebrafisy.

See the website for details on how to apply.