Maureen M. Barr
Associate Professor

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.

Selected Publications

Bae YK, Barr MM. (2008) Sensory roles of neuronal cilia: Cilia development, morphogenesis, and function in C. elegans. Front Biosci. 13:5959-74.

Bae YK, Lyman-Gingerich J, Barr MM, Knobel KM. (2008) Identification of genes involved in the ciliary trafficking of C. elegans PKD-2. Dev Dyn. Apr 13. [Epub ahead of print]

Jauregui AR, Nguyen KC, Hall DH, Barr MM. (2008) The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure. J Cell Biol. 180(5):973-88.

Knobel KM, Peden EM, Barr MM. (2008) Distinct protein domains regulate ciliary targeting and function of C. elegans PKD-2. Exp Cell Res. 314(4):825-33.

Liu T, Kim K, Li C, Barr MM. (2007) FMRFamide-like neuropeptides and mechanosensory touch receptor neurons regulate male sexual turning behavior in Caenorhabditis elegans.
J Neurosci. 27(27):7174-82.

Hu, J., Wittekind, S.G., and Barr, M.M. (2007) STAM and Hrs downregulate ciliary receptors and signaling in C. elegans. Molecular Biology of the Cell 18(9):3277-89.

Bae, Y-K., Qin, H., Knobel, K.M., Hu, J., Rosenbaum, J.L. and Barr, M.M. (2006) General and cell type specific mechanisms target TRPP2/PKD-2 to cilia. Development 133:3859-3870.

Hu, J., Bae, Y.K., Knobel, K.M. and Barr, M.M. (2006) Regulation of ciliary sensory receptors by opposing activities of casein kinase II and calcineurin, Molecular Biology of the Cell 17:2200-11.

Qin, H., Burdette, D., Bae, Y.K., Forscher, P., Barr, M.M., and Rosenbaum, J.L. (2005). Intraflagellar transport is required for the vectorial movement of TRPV channels in the ciliary membrane. Current Biology 15:1695-9.

Jauregui, A.R. and Barr, M.M. (2005) Functional characterization of the C. elegans nephrocystins NPHP-1 and NPHP-4 and their role in cilia and male sensory behaviors. Experimental Cell Research 305:333-42.

Peden, E. M. and Barr, M.M. (2005) KLP-6 is a kinesin required for polycystin ciliary localization and male mating behavior in Caenorhabditis elegans. Current Biology 5: 394-404.

Hu, J. and Barr, M. M. (2005) The PLAT domain of LOV-1 interacts with ATP-2 to regulate polycystin signaling in C. elegans. Molecular Biology of the Cell 16:458-469

Barr, M.M., DeModena, J., Braun, D.,Nguyen, C.Q,. Hall, D.H. and Sternberg, P. (2001) The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway. Current Biology 11:1341-6.

Qin, H., Rosenbaum, J.S., and Barr, M.M. (2001) An ARPKD gene homologue is involved in Intraflagellar transport in C. elegans ciliated sensory neurons. Current Biology 11:457-461.

Barr, M.M. and Sternberg, P. (1999) A polycystic kidney-disease gene homologue required for male mating behaviour in Caenorhabditis elegans. Nature 401:386-389.

Invited Reviews

Barr, M.M. and Garcia, L.R. (2005) Book Chapter “Male mating behavior” in “WormBook,”ed. Martin Chalfie, Electronic publication, www.wormbook.org.

Barr, M.M. (2005) C. elegans as a Model of Renal Development and Disease: Sexy Cilia. Journal of the American Society for Nephrology 16:305-312.