Susan K. Dutcher, Ph.D.

Cell Biology and Physiology

Molecular Genetics and Genomics Program
Molecular Cell Biology Program
Human and Statistical Genetics Program
Plant and Microbial Biosciences Program

Research Abstract:

Cilia are implicated directly in multiple developmental and homeostatic processes that include 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 left-right asymmetry. Although the exact role has not been elucidated, sensory cilia present on neuronal cells have a variety of receptors embedded in their ciliary membrane. Centrioles/basal bodies are highly conserved structures that fulfill important cellular functions, such as nucleation of cilia and flagella and organization of pericentriolar material to form the centrosome for spindle assembly and function. Because of the conservation of these organelles, we use a model organism (Chlamydomonas) to study cilia and basal bodies using genetics, biochemistry, microscopy, and computational biology techniques to understand how they are assembled and function. Recently, we have become interested in a unique region that is found between the plasma membrane and the ciliary membrane; this region is called the transition zone. We are interested in two structures called the ciliary necklace and the ciliary bracelet. Using established mutants as well as forward screens coupled to whole genome sequencing, we have identified mutants lacking the ciliary necklace and one class of mutants with an expanded ciliary bracelet. We are using proteomics to understand their role in transport and recycling of ciliary proteins. Genes of particular interest include CNK10 and RPGRIP1L. We are also interested in motile cilia and how motor proteins are assembled and docked on the cilia of the respiratory tract where they help to move bacteria and viruses out of the lungs. Finally, we are interesting in understanding the assembly of basal bodies and the control of their duplication using forward genetics together with EM tomography to analyze their phenotypes.

Selected Publications:

Cao, M., Ning J., Hernandez, C.I., Belzile, O., Wang, Q., Dutcher, S.K., Liu, Y., and Snell, W.J. (2015). Uni-directional ciliary membrane protein trafficking by a cytoplasmic retrograde IFT motor and ciliary ectosome shedding. eLife, 4:e05242. PMC4362204.

O’Toole, E. and Dutcher, S. K. (2014). Site-specific basal body duplication in Chlamydomonas. Cytoskeleton 71: 108-118. PMCID: PMC4067263

Lin, H., Miller, M.L., Granas, D.M., and Dutcher, S.K. (2013). Whole genome sequencing identifies a deletion in protein phosphatases 2A that affects its stability and localization in Chlamydomonas reinhardtii. PLoS Genetics 9: e1003841. PMCID:PMC3784568

Horani A., Druley TE, Zariwala MA, Levinson BA, Van Arendonk LG, Thornton KC, Giacalone JC, Albee AJ, Wilson KS, Turner EH, Nickerson DA, Shendure J, Patel AC, Bayly PV, Leigh MW, Knowles MR, Brody SL, Dutcher SK, and Ferkol TW. (2012). Whole exome capture and sequencing identifies HEATR2 mutation as a cause of primary ciliary dyskinesia AJHG, 91:685-693.

Bayly P, Lewis BL, Ranz E, Okamoto R, Pless RB and Dutcher SK. Propulsive forces on the flagellum during locomotion of Chlamydomonas reinhardtii. Biophys J. 2011 27: 16-25.

Lin H, Kwan, AL, and Dutcher SK. Synthesizing and salvaging NAD+: Lessons learned from Chlamydomonas reinhardtii. PLoS Genet. 2010 Sep 9;6(9). pii: e1001105.

Bayly P, Lewis BL, Kemp PL, Pless RB, and Dutcher SK. High-resolution spatiotemporal analysis of the flagellar waveform of Chlamydomonas reinhardtii Cell Motil 2010 67:56-69.

Iomini C, Li L, Esparza JM, and Dutcher, S.K.(2009). Retrograde IFT mutants identify complex A proteins with multiple genetic interactions in Chlamydomonas reinhardtii. Genetics 183:885-896.

Iomini C, Li L, Mo W, Dutcher SK, Piperno G. T (2006). Two flagellar genes, AGG2 and AGG3, mediate orientation to light in Chlamydomonas. Current Biology 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.

Last Updated: 8/11/2015 5:03:30 PM

The ciliary bracelet using quick freeze deep etch microscopy
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