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Brill Lab

Brief Biography

• BA with Distinction in Biology, Swarthmore College, Swarthmore, PA.
• PhD in Biology with Dr. Gerald R. Fink, Massachusetts Institute of Technology, Cambridge, MA.
• Postdoctoral training at Stanford University School of Medicine with Dr. Margaret T. Fuller and at the University of Washington with Dr. Barbara T. Wakimoto.
• Recipient of Leukemia and Lymphoma Society Special Fellowship.

Research Interests

• cell morphogenesis
• phosphatidylinositol lipids
• membrane trafficking
• cytoskeleton
• cytokinesis
• spermatogenesis
• developmental biology
• cancer

Research Activities

My lab uses the fruit fly as a model system for studying sperm development. Using a combination of molecular genetics and modern cell biological techniques, we found that a class of membrane lipids called phosphatidylinositol phosphates (PIPs) is important for cytokinesis (the splitting of one cell into two) and sperm tail formation.

We showed that hydrolysis of PIP2, a key regulatory phospholipid, and calcium release are required during cytokinesis. Failure of either of these steps results in unstable cleavage furrows and cytokinesis failure. Depletion of PIP2 causes cytokinesis failure and defects in microtubule organization during sperm development, resulting in sterile flies.

Future Research Interests

Our current research focuses on the roles of three PI 4-kinases - enzymes that control cellular levels of PIPs - in fly development. We found that Fwd (fly PI4KIIIbeta) regulates membrane trafficking to the cleavage furrow during cytokinesis. PI4KIIIalpha controls membrane trafficking and actin organization at the plasma membrane in developing oocytes. PI4KII regulates secretory granule formation in salivary gland cells and controls pigmentation in the fly eye. In addition, we have identified a role for PIP2 in determining the polarity of developing fruit fly sperm.

Our future studies will identify the targets of regulation by PI 4-kinases and PIPs at different stages of fly development. Since these important enzymes and membrane lipids are conserved - and since development of fruit flies and humans is quite similar at the cellular level - we expect our research to lead to a better understanding of the roles for these enzymes and lipids in normal human development and disease.

External Funding

• CIHR
• NSERC
• CRS

Publications

Brill, J. A., Wong, R. and Wilde, A. (2011) Phosphoinositide function in cytokinesis. Current Biol 21:R930-R934.

Burgess, J., Jauregui, M., Tan, J., Rollins, J., Lallet, S., Leventis, P. A., Boulianne, G. L., Chang, H. C., Le Borgne, R., Krämer, H. and Brill, J. A. (2011) AP-1 and clathrin are essential for secretory granule biogenesis in Drosophila. Mol Biol Cell 22: 2094-2105. [Featured in High Mag blog.]

Szul, T., Burgess, J., Jeon, M., Marques, G., Brill, J. A. and Sztul, E. (2011) The Garz Sec7 domain guanine nucleotide exchange factor for ARF regulates salivary gland development in Drosophila. Cellular Logistics 1: 69-76. [Cover article.]

Zhou, X., Fabian, L., Bayraktar, J. L., Ding, H.-M., Brill, J. A. and Chang, H. C. (2011) Auxilin is required for formation of Golgi-derived clathrin-coated vesicles during Drosophila spermatogenesis. Development 138: 1111-1120. [Cover article.]

Goldbach P, Wong R, Beise N, Sarpal R, Trimble WS, Brill JA. Stabilization of the actomyosin ring enables spermatocyte cytokinesis in Drosophila. Mol Biol Cell 21: 1482-93. [Featured in High Mag blog.]

Fabian L, Wei H-C, Rollins J, Noguchi T, Polevoy G, Blankenship JT, Bellamkonda K, Gervais L, Guichet A, Fuller MT, Brill JA. PIP2 directs spermatid cell polarity and exocyst localization in Drosophila. Mol Biol Cell 21: 1546-55. [Cover article.]

Polevoy G, Wei H-C, Wong R, Szentpetery Z, Kim YJ, Goldbach P, Steinbach SK, Balla T, Brill JA. Dual roles for the Drosophila PI 4-kinase Fwd in regulating Rab11 localization during cytokinesis. J Cell Biol 187; 847-58. [Reviewed in Faculty of 1000 Biology]

Wei H-C, Rollins J, Fabian L, Hayes M, Polevoy G, Bazinet C, Brill JA. (2008) Depletion of plasma membrane PtdIns(4,5)P2 reveals essential roles for phosphoinositides in flagellar biogenesis. J Cell Sci, 121: 1076-84. [Cover article.]

Wong R, Fabian L, Forer A, Brill JA. (2007) Phospholipase C and myosin light chain kinase inhibition define a common step in actin regulation during cytokinesis. BMC Cell Biology 8: 15.

Parsons AB, Lopez A, Givoni IE, Williams DE, Gray C, Porter J, Chua G, Sopko R, Brost RL, Ho C-H, Wang J, Ketela T, Brenner C, Brill JA, Fernandez GE, Lorenz TC, Payne GS, Ishihara S, Ohya Y, Andrews B, Hughes TR, Frey BJ, Graham TR, Andersen RJ, Boone C. (2006) Exploring the mode-of-action of bioactive compounds by chemical-genetic profiling in yeast. Cell 126: 611-25.

Jin Z, Homola EM, Goldbach P, Choi YH, Brill JA, Campbell SD. (2005) Drosophila Myt1 is a Cdk1 inhibitory kinase that regulates multiple aspects of cell cycle behavior during gametogenesis. Development 132: 4075-85.

Wong R, Hadjiyanni I, Wei H-C, Polevoy G, McBride R, Sem K.-P, Brill JA. (2005) PIP2 hydrolysis and calcium release are required for cytokinesis in Drosophila spermatocytes. Current Biology 15: 1401-06.
[Featured in Nature, “Research Highlights,” Aug. 18, 2005.]

Saul D, Fabian L, Forer A, Brill JA. (2004) Continuous phosphatidylinositol metabolism is required for cleavage of crane-fly spermatocytes. J. Cell Sci. 117: 3887-96.
[Cover article. Featured in Albertson R, Riggs B, Sullivan W., Trends in Cell Biology (2005) 15:92-101.]

Wei H-C, Sanny J, Shu H, Baillie DL, Brill JA, Price JV, Harden N. (2003) The Sac1 lipid phosphatase regulates cell shape change and the JNK cascade during dorsal closure in Drosophila. Current Biology 13: 1882-87.

Xu H, Brill JA, Hsien J, McBride R, Boulianne GL, Trimble WS. (2002) Syntaxin 5 is required for cytokinesis and spermatid differentiation in Drosophila. Developmental Biology 251: 294-306.

Brill JA, Hime GR, Scharer-Schuksz M, Fuller MT. (2000) A phospholipid kinase regulates actin organization and intercellular bridge formation during germline cytokinesis. Development, 127:3855-3864.

Hime GR, Brill JA, Fuller MT. (1996) Assembly of ring canals in the male germ line from structural components of the contractile ring. J. Cell Sci., 109:2779-2788.