Molecular Cell & Developmental Biology
225 Sinsheimer Laboratories
Phone: 831.459.4986
Fax: 831.459.3139
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WILLIAM SULLIVAN Professor of MCD Biology B.A., University of California, San Diego Ph.D., University of Washington, Seattle SULLIVAN LAB

225 Sinsheimer Laboratories University of California Santa Cruz, CA 95064 phone 831.459.4295 fax 831.459.3139 sullivan@biology.ucsc.edu office hours

The molecular and cellular mechanisms driving cytokinesis. Animal cytokinesis relies on acto-myosin based constriction of the plasma membrane to produce two daughter cells.  Recent studies from a number of labs, including ours, demonstrate that membrane addition during cytokinesis plays an essential role as well. Our long term objective is to understand the role of membrane addition in key events of cytokinesis including the timing and positioning of contractile ring formation, recruiting and assembling contractile ring components, and furrow progression.  We have identified a link between vesicle-based membrane addition from the recycling endosome and the initial organization of F-actin at the site of cleavage furrow formation.  Currently, our focus is on addressing the following issues: What are the mechanisms that recruit and stabilize F-actin at the cleavage furrows?   How is vesicle-mediated membrane addition to the cleavage furrow coordinated with other mitotic events?  Which membrane trafficking components are specifically required for cytokinesis?

Genetic and Cellular Analysis of Bacteria-Host Interactions: Interactions between microbes and eukaryotic hosts have independently evolved numerous times during the history of life on our planet. We are interested in the defining the interactions between Wolbachia and its host at the cellular level. Wolbachia are obligate intracellular bacterial endosymbionts present in millions of insect species.  Manipulation of host reproduction and efficient maternal transmission have facilitated the global spread of Wolbachia.   Wolbachia are also present in worms and are the leading cause of blindness in Southern African due the inflammatory response upon release from their nematode host Onchocerca volvulus.  Our long term objective is to understand  how Wolbachia use and manipulate host cell machinery to their reproductive advantage.  Specifically we are interested in the host cellular events involved in Wolbachia-induced cytoplamic incompatibility (CI), maternal-transmission, germline incorporation and replication.   We will address these issues the natural host Drosophila melanogaster.  This is an excellent system as it is amenable to molecular, genetic and cellular approaches. Studies in our lab and others have demonstrated that the microtubule cytoskeleton plays a key role in Wolbachia transmission.  While interactions between intracellular pathogens and the host actin cytoskeleton have been intensively investigated, those between pathogens and the microtubule cytoskeleton remain largely unexplored.  Thus the Wolbachia-Drosophila system provides a powerful system for investigating pathogen interactions with the host microtubule cytoskeleton.

The role of cell cycle checkpoints during embryogenesis.  Recently we discovered that DNA damage produces a Chk1/Grp DNA damage dependent delay in metaphase.  This result is surprising because DNA damage checkpoints were thought to act specifically in interphase while the spindle assembly checkpoint in metaphase.  Currently we are using a combination of genetic, biochemical and cellular approaches to address the following issues: Does DNA repair occur during the checkpoint induced metaphase-arrest?  What is the molecular mechanism by which Chk1/Grp mediates a DNA damage induced metaphase delay.  Do DNA damage checkpoints alter the fate of acentric chromosome fragments induced by double-strand breaks?

Using the Drosophila embryonic divisions for real time profiling of anti-cancer drugs  The speed of the cortical syncytial divisions, combined with the ability to perform detailed real-time imaging, has enabled us to perform unprecedented detailed real-time morphological phenotypic analysis of cell cycle mutations. This analysis motivated us to perform similar studies with cell cycle inhibitors and anti-cancer drugs. A key advantage of this type of analysis is that it provides detailed temporal as well as morphological information on the effects of experimental therapies.


Selected Publications
Tram U, Fredrick K, Werren JH, Sullivan W.  (2006) Paternal chromosome segregation during the first mitotic division determines Wolbachia-induced cytoplasmic incompatibility phenotype.  J Cell Sci. 119: 3655-63.

Ferree PM, Sullivan W.  (2006) A Genetic Test of the Role of the Maternal Pronucleus in Wolbachia-Induced Cytoplasmic Incompatibility in Drosophila melanogaster.
Genetics 173(2): 839-47.

Ferree, P.M., McDonald, K., Fasulo, B., Sullivan, W.T. (2006) The origin of Centrosomes in Parthenogenetic Hymenopteran Insects.  Current Biol. 16: 801-807.

Albertson, R., Riggs, B., and Sullivan, W. (2005) Membrane traffic: a driving force in cytokinesis. Trends Cell Biol 15: 92-101.

Royou, A., Macias, H., and Sullivan, W. (2005) The Drosophila Grp/Chk1 DNA damage checkpoint controls entry into anaphase. Curr Biol, 15: 334-339.

Field, C.M., M. Coughlin, S. Doberstein, T. Marty, W. Sullivan.  (2005) Characterization of scraps mutants reveals an essential role for anillin in septing localization and cortex/plasma membrane integrity. Development 132: 2849-2860.

Kidd, T., R. Abu-Shumays, A.Katzen, J. Sisson, G.Jimenez, S. Pinchin, W. Sullivan, D. Ish-Horowicz. (2005) The epsilon subunit of mitochondrial ATP synthase is required for normal spindle orientation during the Drosophila embryonic divisions.  Genetics 170: 697-708.

Ferree, P.M., H.M. Frydman, J.M. Li, J. Cao, E. Wieschaus, W. Sullivan. (2005) Wolbachia utilize host microtubules and dynein for anterior localization in the Drosophila oocyte.  PLoS Pathogens 2: 0111-0124.

Royou, A., C. Field, J. Sisson, W. Sullivan and R. Karess (2004). Reassessing the role and dynamics of nonmuscle myosin II during furrow formation in early Drosophila embryos. Mol Biol Cell, 15: 838-850.

Tram, U., P. Ferree, and W. Sullivan. (2003) Identification of Wolbachia-host interacting factors through cytological analysis.  Microbes Infect 5(11): 999-1011.

Riggs, B., W. Rothwell, S. Mische, G.R.X. Hickson, G.W. Gould, T. Hays, and W. Sullivan. (2003) Actin cytoskeleton remodeling during early Drosophila furrow formation requires recycling endosomal components Nuclear-fallout and Rab11. Journal of Cell Biology, 163: 143-154.

Hickson G.R.X., J. Matheson, B. Riggs, V.H. Maier, A.B. Fielding, R. Prekeris, W. Sullivan, F.A. Barr, and G.W. Gould. (2003) Arfophilins are dual arf/rab11 binding proteins that regulate recycling endosome distribution and are related to Drosophila Nuclear-fallout. Molecular Biology of the Cell, 14: 2908-20.

Royou, A., W. Sullivan and R. Karess (2002). Cortical recruitment of nonmuscle myosin II in early syncytial Drosophila embryos: its role in nuclear axial expansion and its regulation by Cdc2 activity. Journal of Cell Biology, 158:127-137.

Tram, U., and W. Sullivan (2002) Role of delayed nuclear envelope breakdown and mitosis in Wolbachia-induced cytoplasmic incompatibility. Science. 296: 1124-1126.

Tram, U., B. Riggs, and W. Sullivan (2001). Cleavage and gastrulation in Drosophila embryos. Encyclopedia of Life Sciences. Macmillan Reference Ltd. In Encyclopedia of Life Sciences. Nature Publishing Group. London. www.els.net.

Debec, A., M. Grammont, G. Berson, B. Dastugue, W. Sullivan, J.L. Couderc. (2001) Toucan protein is essential for the assembly of syncytial mitotic spindles in Drosophila melanogaster. Genesis. 31: 167-175.

Tram, U., B. Riggs, C. Koyama, A. Debec, and W. Sullivan (2001). Methods for the study of centrosomes in Drosophila during embryogenesis. In Methods in Cell Biology: Centrosomes and Spindle Pole Bodies. R.E. Palazzo and T.N. Davis, Editors. Academic Press. San Diego. 67: 113-123.

Tram, U. and W. Sullivan (2001). Live confocal analysis of fertilization and early development. Microscopy and Microanalysis 7, 1012-1013.

MacDougall, N., Y. Lad, G.S. Wilke, H. Francis-Lang, W. Sullivan, and I. Davis (2001). Merlin, the Drosophila homologue of neurofibromin 2, is specifically required in posterior follicle cells for axis formation in the oocyte. Development 128, 665-673.

Sisson, J.C., C. Field, R. Ventura, A. Royou, and W. Sullivan. (2000) Lava Lamp, a Novel Peripheral Golgi Protein, Is Required for Drosophila melanogaster Cellularization. J. Cell Biol.151:905-918.

Morris, R.L., H.L. Brown, B.D. Wright, D.J. Sharp, W. Sullivan, and J.M. Scholey. (2001) Microinjection methods for analyzing the functions of kinesins in early embryos. Methods in Molecular Biology 164: 163-172.

Tram, U. and W. Sullivan. (2000) Reciprocal inheritance of centrosomes in the parthenogenetic Hymenopteran Nasonia vitripennis. Current Biology10:1413-1419.

Yu K. R., R. Saint, and W. Sullivan. (2000) The Grapes checkpoint coordinates nuclear envelope breakdown and chromosome condensation. Nature Cell Biology2:609-615.

Rothwell, W.F. and W. Sullivan. (2000) The centrosome in early Drosophila embryogenesis. Current Topics Developmental Biology 49:409-447.

Zhang C. X., W.F. Rothwell, W. Sullivan and T. Hsieh. (2000) Discontinuous actin hexagon, a protein essential for cortical furrow formation in Drosophila is membrane associated and hyper-phosphorylated. Molecular Biology of the Cell11:1011-1022.