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The Barr laboratory is interested in two seemingly unrelated questions in biology: the generation of sexual behaviors 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. We use several approaches to study animal physiology and behavior, including dissection of neural circuits, the identification of genes required for nervous system development and function, in vivo imaging of neuronal protein trafficking, and, most recently, electrophysiology. C. elegans has been an outstanding model for studying sexual dimorphism at the levels of X-chromosome dosage compensation, germ line and somatic sex determination, and anatomical development. Very little is known regarding the molecular genetic determinants of sexual dimorphism in the C. elegans adult nervous system. The core nervous system (shared between hermaphrodites and males) is composed of 294 neurons. The sex-specific nervous system has eight hermaphroditic and 89 male-specific neurons. We have identified genes that act in the core and male-specific nervous systems to regulate mating behaviors. How do these core and sex-specific nervous systems communicate? How do gender-specific modifications of the core nervous system contribute to copulatory behaviors? Genetics coupled with ongoing reconstruction of the male C. elegans nervous system (by David Hall and Scott Emmons at Albert Einstein) will enable us to identify the molecular pathways and neural circuitries that generate complex behaviors. Cilia are motile or sensory organelles found on almost every non-dividing human cell. The mechanism of ciliary development is evolutionarily conserved in organisms ranging from alga to man. In contrast, the processes governing ciliary specialization are not known. Recent studies have revealed that defects in cilia are linked to human cystic kidney diseases. C. elegans is an exceptional model for the study of cilia-related human diseases. The simple and transparent anatomy of C. elegans enables visualization of ciliogenesis and ciliary transport in a living organism. In addition to the 60 core ciliated sensory neurons, the male possesses 48 sex-specific ciliated neurons. All of these cilia exhibit diverse morphologies and express distinct sensory receptors on their surface. Many of the genes required for the formation, maintenance, and function of C. elegans cilia have human counterparts that, when mutated, cause diseases with renal pathologies. Our laboratory has successfully developed C. elegans cystic kidney disease models and is in the unique position to address the underlying molecular bases and interconnections of these devastating disorders.
Barr Lab Publications (last 3 years) 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. 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.
Lab Support Dr. Juan Wang, Research Associate |
Research
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