In vertebrates, cilia are indispensible cellular organelles that regulate cell development and signaling in response to changes in the external environment. Cilia are found on many different human cell types and play a role in a variety of cell functions. Dysfunctional cilia contribute to a number of different human developmental defects and diseases including congenital heart defects, autosomal dominant polycystic kidney disease, and obesity. The focus of this project is on understanding how proper protein receptor localization contributes to cilia function and appropriate responses to the environment. In order to address this broad question, this project will focus on receptor localization in primary cilia of the nematode, Caenorhabditis elegans. Two mutant strains of C. elegans will be studied: xbx-1(my17) mutants and cil-5(my13) mutants have defects in localization of PKD-2, a receptor which localizes to cilia of male-specific neurons. Both of these mutants are characterized by extensive defects in cilia-mediated sensory behaviors. In order to characterize retrograde transport, known proteins involved in transport and putative XBX-1 interact ring proteins will be analyzed using GFP fusion constructs in the xbx-1(my17) mutant background. The cil-5(my13) mutants will be tested for defects in a variety of sensory behaviors including chemosensation, osmosensation, and mating. In addition, preliminary data suggest that lipid storage in the cil- 5(my13) mutants is increased compared to wild-type suggesting that understanding the role of the cil-5 gene will be relevant for cilia diseases for which obesity is a symptom. This result will be further analyzed both by fluorescent microscopy analysis of lipid indicators and genetic analysis of cil-5(my13);bbs-1(mg409) doubles mutants. Additional genes involved in protein receptor localization to cilia will be identified by using RNAinterference to identify factors affecting PKD-2 localization. The results of this project will provide insight into several areas of cilia biology, including localization of ciliary receptors, retrograde transport, and specialization of cilia. In addition, these results will provide important insight into the links between cilia signaling and human health, including heart development, fat storage and obesity, and polycystic kidney disease.

Public Health Relevance

This research aims to investigate the link between cilia (organelles found on most types of human cells) and maintenance of human health by identifying the genes involved in cilia function and specialization. Through genetic analysis of cilia in the nematode, C. elegans, the project focuses on identifying how improper cilia signaling can contribute to such diverse symptoms as obesity and congenital heart defects.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Academic Research Enhancement Awards (AREA) (R15)
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Special Emphasis Panel (ZRG1-CB-N (52))
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Haft, Carol R
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University of Wisconsin Eau Claire
Schools of Arts and Sciences
Eau Claire
United States
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Braunreiter, Kara; Hamlin, Shelby; Lyman-Gingerich, Jamie (2014) Identification and characterization of a novel allele of Caenorhabditis elegans bbs-7. PLoS One 9:e113737