Centriole Biogenesis for Centrosomes and Cilia
Microtubules are responsible for diverse cellular functions, ranging from trafficking and force generation to structural platforms for cellular sensation. Variations in microtubule function are achieved because their fascinating structures and dynamics can be modulated by different microtubule organizing centers (MTOC) and regulatory events. Integral to microtubule organization is the centriole, the core structure around which vertebrate centrosomes and cilia are assembled. Increasingly appreciated in human disease, defects in centrioles, centrosomes, and cilia contribute to both human cancer and ciliary diseases, or ciliopathies, that exhibit an array of pathologies including polydactyly, situs inversus, kidney cysts, blindness, respiratory illness, and mental retardation. This diversity in pathologies is a result of the many specialized cellular processes in which centrioles and cilia function to generate forces or to sense the surrounding environment.
Our lab is focused on the structural and molecular events for centriole biogenesis. Electron microscopy studies performed a half a century ago defined the morphological events leading to a mature centriole. However, the hundreds of molecules that comprise these structures were unknown. Now with a large inventory of centriole components from proteomic studies, we can explore how these proteins collaborate to assemble the nine-fold radially symmetric centriole structure. To do so, the lab is focused on several projects:
1) Determine the centriole cartwheel proteome.
2) Identify the functional complexes of the centriole.
3) Determine the localization domains and dynamics of centriole proteins.
4) Determine how centrioles mature and stabilize to resist to mechanical forces.
We use multiple model systems in conjunction with electron and high-resolution, quantitative fluorescence microscopy. We have developed Tetrahymena thermophila for molecular studies of centriole assembly and function. This ciliated protist, with its 750 centrioles per cell, is a fantastic system to study the assembly process. Tetrahymena has the unique advantage of genetic manipulability combined with hundreds of centriole assembly events per cell cycle. Results found for Tetrahymena are often expanded upon in our studies of human centrioles.
Thomas H. Giddings, Jr., Janet B. Meehl, Chad G. Pearson and Mark Winey (2010) Electron tomography and immuno labeling of Tetrahymena thermophila basal bodies. Meth. Cell Biol. (in press).
Chad G. Pearson, Daniel P.S. Osborne, Thomas H. Giddings Jr., Philip L. Beales, and Mark Winey. (2009) Basal body stability and ciliogenesis requires the conserved component Poc1. J. Cell Biol. 187(6) 905-20.
Chad G. Pearson, Thomas H. Giddings, and Mark Winey. (2009) Basal body components exhibit differential protein dynamics during nascent basal body assembly. Mol. Biol. Cell. 20(3) 904-914.
Chad G. Pearson and Mark Winey (2009) Basal body assembly in ciliates: the power of numbers. Traffic. 10(5) 461-471.
Chandra L. Kilburn*, Chad G. Pearson*, Edwin P. Romijn, Janet B. Meehl, Thomas H. Giddings, Jr., Brady P. Culver, John R. Yates III, and Mark Winey. (2007) New Tetrahymena basal body protein components identify basal body domain structure. J. Cell Biol. 178(6) 905-912. *Equal contribution
Philip L Beales, Elizabeth Bland, Jonathan L. Tobin, Chiara Bacchelli, Josephine Hill, Suzanne Rix, Chad G. Pearson, Masa Kai, Jane Hartley, Colin Johnson, Melita Irving, Nursel Elcioglu, Beyhan Tuysuz, Mark Winey, Masa Tada, Peter J. Scambler. (2007) IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy. Nat. Gen. 39(6) 727-729.
Chad G. Pearson, Brady Culver, and Mark Winey (2007) Centrioles want to move out and make cilia. Dev. Cell. 13(3) 319-321.
Chad G. Pearson, Melissa K. Gardner, Lecadia V. Paliulis, E.D. Salmon, David J. Odde, and Kerry Bloom. (2006) Measuring Nanometer Scale Gradients in Spindle Microtubule Dynamics Using Model Convolution Microscopy. Mol. Biol. Cell. 17(9) 4069-4079.
Chad G. Pearson, Elaine Yeh, Melissa Gardner, David Odde, E.D. Salmon and Kerry Bloom. (2004) Stable kinetochore-microtubule attachment constrains centromere positioning in metaphase. Curr Biol. 14(21) 1962-1967.
Chad G. Pearson and Kerry Bloom. (2004) Dynamic microtubules lead the way for spindle positioning. Nat Rev Mol Cell Biol. 5(6) 481-492.
Chad G. Pearson, Paul S. Maddox, Ted R. Zarzar, Edward D. Salmon and Kerry Bloom (2003) Yeast Kinetochores Do Not Stabilize Stu2p-dependent Spindle Microtubule Dynamics. Mol. Biol. Cell. 14(10) 4181-4195.
Chad G. Pearson, Paul S. Maddox, E.D. Salmon, and Kerry Bloom (2001) Budding yeast chromosome structure and dynamics during mitosis. J. Cell Biol. 152(6) 1255-1266.