Roles of cilia and mechanisms of ciliogenesis in animal development

Wheaton College, Norton MA

Investigators

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Abstract

DESCRIPTION (provided by applicant): Cilia are complex and essential cellular machines that propel fluid over cells and sense stimuli in the environment. Recent discoveries about the central role that ciliary defects play in many human diseases and birth defects have energized the field of ciliary research. Motile cilia play critical roles in defining body axes in the early vertebrate embryo, and sensory cilia transduce fate-determining signals after body axes are set. But while lists of ciliary components and basic mechanisms of ciliogenesis have been identified in the single celled Chlamydomonas and the nematode Caenorhabditis elegans, model systems that express the variety of cilia found in humans with the complex regulative development found in humans are few. To uncover how ciliogenesis in developing organisms can produce motile propulsive and immotile sensory cilia with a spectrum of tissue-specific morphologies and functions, the principal investigator proposes to study ciliogenesis in early sea urchin embryos. With a research team of exclusively undergraduate collaborators, he has identified the cytoskeletal and motor protein genes in the recently completed sea urchin genome assembly and now wish to apply these discoveries to the developmentally critical process of ciliogenesis. He proposes to investigate the roles of cilia and ciliary proteins in the early animal development to better understand the processes that lead to birth defects. By combining cell biological and genomics approaches, the investigator and students will a.) define a ciliary proteome to identify proteins with potential importance in ciliogenesis and thereby, in development, b.) characterize the patterns of ciliogenesis and the roles of ciliogenic proteins by microscopy and gene knock-downs, and c.) identify other marine models in which to study mechanisms of ciliogenesis outside of sea urchin season. Carrying out this research plan at Wheaton College during the year and at the Marine Biological Laboratory during the summers will allow the investigator and his students to clarify the basic mechanisms of ciliogenesis among deuterostomes, and thereby improve our understanding of many human diseases and birth defects recently discovered to be cilia-based. PUBLIC HEALTH RELEVANCE: Cilia are long appendages of cells that beat like paddles to move fluid over the cell or stand straight like antennae to receive signals from the outside world. Because embryonic cilia help coordinate development and adult cilia help maintain ion balance and move fluids in lungs and reproductive tracts, defects in cilia produce a spectrum of birth defects and human diseases. To better understand human ciliary disease, the investigator's laboratory studies mechanisms of cilia formation on sea urchin embryos where a similar variety of ciliary forms to those in humans exist and where ciliary defects can be readily modeled, analyzed, and understood.