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, super resolution in vivo imaging of ciliary transport and extracellular vesicle (EV) shedding, and EV biochemistry/EVomics.

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 such as autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive PKD, Nephronophthisis (NPHP), Bardet-Biedl Syndrome (BBS), and Meckel Gruber Syndrome (MKS). 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 as a model to study ADPKD, NPHP, and MKS and is in the unique position to address the underlying molecular bases and interconnections of these devastating disorders.

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