Research Abstract:
Cilia and basal bodies have been implicated directly in several developmental processes including left-right asymmetry, heart development, maintenance of the renal epithelium, respiratory function, electrolyte balance in the cerebrospinal fluid, and reproductive fecundity. Nodal cilia in early development are fundamental to initiate the molecular cascade that ultimately leads to the visceral asymmetry in. A lack or dysfunction of sensory cilia in the epithelium of renal tubules underlies polycystic kidney disease, although the exact process of cyst formation is not understood. In the retina, successful translocation of several molecules from the cell body to the outer segment of the photoreceptor depends on transport along a modified cilium; defective transportation of certain proteins results in the retinal degeneration associated with retinitis pigmentosa. Although the exact role has not been elucidated, sensory cilia present on neuronal cells have somatostatin receptors embedded in their ciliary membrane. Defective basal bodies have been implicated in the pathogenesis of the pleiotropic Bardet-Biedl syndrome (BBS). This multisystemic disorder is characterized by retinal dystrophy, obesity, renal malformations, and learning disabilities. We use Chlamydomonas reinhardtii as a model system to study these organelles using genetics, biochemistry, microscopy, and computational biology techniques to understand how they are assembled and function. We have developed antibodies for six of the BBS genes and they are localized to the the basal body regions. RNA interference can be used to “knockdown” the message level and examine the phenotypes of novel genes as well as homologs of known human disease genes.
Selected Publications:
Dutcher SK. Finding treasures in frozen cells: New centriole intermediates. Bioessays 2007 29:630-634.
Iomini C, Li L, Mo W, Dutcher SK, Piperno G. Two flagellar genes, AGG2 and AGG3, mediate orientation to light in Chlamydomonas. Current Biology 2006 16:1147-1153.
Li JB, Gerdes JM, Haycraft CJ, et al. Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell 2004 117:541-552.
Dutcher SK. Elucidation of basal body and centriole functions in Chlamydomonas reinhardtii. Traffic 2003 4:443-451.
O'Toole ET, Giddings TH, McIntosh JR, Dutcher SK. Three-dimensional organization of basal bodies from wild-type and delta-tubulin deletion strains of Chlamydomonas reinhardtii. Mol Biol Cell 2003 14:2999-3012.
Last Updated: 11/20/2007 |