C. elegans cilia development, morphogenesis, and function: a human disease model
The Barr laboratory is interested two seemingly unrelated questions in biology: the generation of sexual identity and the molecular basis of human genetic diseases of cilia. In particular, we study male mating behavior and ciliary specialization in the nematode Caenorhabditis elegans. My laboratory currently uses several approaches to study animal physiology and behavior, including dissection of neural circuits, the identification of genes required for nervous system development and function, and in vivo imaging of neuronal protein trafficking. Chemical genetics and electrophysiology are being explored.
Several human genetic disorders, including autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive PKD, Nephronophthisis (NPHP), Meckel-Gruber syndrome (MKS) and Bardet-Biedl Syndrome (BBS) share two common features: ciliary localized gene products and kidney cysts. Given that it is prohibitively difficult in humans to study the connection between cilioprotein function, localization, and disease, alternative experimental systems are necessary. In C. elegans it is feasible to study how human disease gene orthologs affect cilia formation, morphogenesis, and signaling. The Barr laboratory has well-established C. elegans models for ADPKD and NPHP, and is currently developing a worm model for MKS, the leading syndromic cause of neural tube defects in humans. Results of our studies will broaden our understanding of how cilia develop, form, and function in normal and pathological states and provide new insight into the molecular basis of human ciliopathies.