Julie Brill , PhD
University of Toronto
Collaborative Program in Developmental Biology
Department of Molecular Genetics
Institute of Medical Science
Alternate Contact: Mary Ann Gueco (Secretary)
Alternate Phone: (416) 813-7654 x303045
- 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 & Lymphoma Society Special Fellowship.
Phosphatidylinositol (PI) phosphates (PIPs) are membrane lipids with critical roles in cell growth, signaling and morphogenesis. Alterations in the levels of PIPs are associated with human diseases such as cancer. However, little is known about the normal roles of PIPs during animal development. My research investigates the roles of PIPs and their regulatory enzymes using powerful molecular genetic approaches available in the fruit fly Drosophila melanogaster. We have created Drosophila mutants and transgenic lines that enable us to perturb and study PIPs in different tissues in the fly. We have also generated transgenic flies expressing fluorescent protein fusions that allow us to examine the distribution of PIPs and PIP pathway targets and enzymes in individual cells and tissues in real time. Using these tools, we have uncovered roles for PI 4-phosphate (PI4P) and PI 4,5-bisphosphate (PIP2) and PIP pathway enzymes in cytokinesis, gametogenesis and organelle biogenesis. Our current studies focus on understanding the roles of PIPs in these processes; deciphering how the activity of PIP regulatory enzymes is controlled in response to cellular and developmental signals; and identifying downstream targets and effectors of PIP signaling. As PIPs and their regulatory enzymes are found in all eukaryotes, our research will identify conserved cellular mechanisms fundamental to human development and disease.
Tan, J. and Brill, J. A. (2014) Cinderella story: PI4P goes from precursor to key signaling molecule. Crit Rev Biochem Mol Biol 49: 33-58. PMID: 24219382
Jović, M., Kean, M. J., Dubankova, A., Boura, E., Gingras, A.-C., Brill, J. A. and Balla, T. (2014) Endosomal sorting of VAMP3 is regulated by PI4K2A. J Cell Sci. Epub date: 7 July 2014.
Tan, J., Oh, K., Burgess, J., Hipfner, D. R. and Brill, J. A. (2014) PI4KIIIα is required for cortical integrity and cell polarity during Drosophila oogenesis. J Cell Sci 125: 954-66. PMID: 24413170. [Cover article]
Murray, M. J., Ng, M. M., Fraval, H., Tan, J., Liu, W., Smallhorn, M., Brill, J. A., Field, S. J. and Saint, R. (2012) Regulation of Drosophila mesoderm migration by phosphoinositides and the PH domain of the Rho GTP exchange factor Pebble. Dev Biol 372: 17-27. PMID: 23000359.
Fabian, L. and Brill, J. A. (2012) Drosophila spermiogenesis: Big things come from little packages. Spermatogenesis 2 (3): 197-212. Open access article (Landes Biosciences). [Cover article.]
Hernández, G., Han, H., Gandin, V., Fabian, L., Ferreira, T., Zuberek, J., Sonenberg, N., Brill, J. A. and Lasko, P. (2012) Eukaryotic initiation factor 4E-3 is essential for meiotic chromosome segregation, cytokinesis and male fertility in Drosophila. Development 139: 3211-3220. PMID: 22833128
Burgess, J., Del Bel, L. M., Ma, C.-I. J., Barylko, B., Polevoy, G., Rollins, J., Albanesi, J. R., Krämer, H. and Brill, J. A. (2012) Type II phosphatidylinositol 4-kinase regulates trafficking of secretory granule cargo in Drosophila. Development 139: 3032-3039. PMID: 22791894 [Cover article.]
Jović, M., Kean, M. J., Szentpetery, Z., Polevoy, G., Gingras, A.-C., Brill, J. A. and Balla, T. (2012) Two PI 4-kinases control lysosomal delivery of the Gaucher disease enzyme, β-glucocerebrosidase. Mol Biol Cell 23: 1533-45. PMID: 22337770
Brill, J. A., Wong, R. and Wilde, A. (2011) Phosphoinositide function in cytokinesis. Current Biol 21: R930-R934. PMID: 22115464
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. PMID: 21490149 [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. PMID: 21686256 [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. PMID: 21343365 [Cover article.]
Fabian, L.,* Wei, H.-C.,* Rollins, J., Noguchi, T., Polevoy, G., Blankenship, J. T., Bellamkonda, K., Gervais, L., Guichet, A., Fuller, M. T. and Brill, J. A. (2010) PIP2 directs spermatid cell polarity and exocyst localization in Drosophila. Mol Biol Cell 21: 1546-1555. PMID: 20237161 [Cover article. Ranked as Excptional in Faculty of 1000.]
Goldbach, P., Wong, R., Beise, N., Sarpal, R., Trimble, W. S. and Brill, J. A. (2010) Stabilization of the actomyosin ring enables spermatocyte cytokinesis in Drosophila. Mol Biol Cell 21: 1482-1493. PMID: 20237160 [Featured in High Mag blog.]
Polevoy, G.,* Wei, H.-C.,* Wong, R., Szentpetery, Z., Kim, Y. J., Goldbach, P., Steinbach, S. K., Balla, T. and Brill, J. A. (2009) Dual roles for the Drosophila PI 4-kinase Fwd in regulating Rab11 localization during cytokinesis. J Cell Biol 187: 847-858. PMID: 19995935 [Reviewed in Faculty of 1000 Biology. Note that this evaluation reached the top 3% of User Accesses at the time of submission.]
Wei, H.-C., Rollins, J., Fabian, L., Hayes, M., Polevoy, G., Bazinet, C. and Brill, J. A. (2008) Depletion of plasma membrane PtdIns(4,5)P2 reveals essential roles for phosphoinositides in flagellar biogenesis. J Cell Sci 121: 1076-1084. PMID: 18334551 [Cover article.]
Wong, R., Fabian, L., Forer, A. and Brill, J. A. (2007) Phospholipase C and myosin light chain kinase inhibition define a common step in actin regulation during cytokinesis. BMC Cell Biol 8: 15. PMID: 17509155
Parsons, A. B., Lopez, A., Givoni, I. E., Williams, D. E., Gray, C., Porter, J., Chua, G., Sopko, R., Brost, R. L., Ho, C.-H., Wang, J., Ketela, T., Brenner, C., Brill, J. A., Fernandez, G. E., Lorenz, T. C., Payne, G. S., Ishihara, S., Ohya, Y., Andrews, B., Hughes, T. R., Frey, B. J., Graham, T. R , Andersen, R. J. and Boone, C. (2006) Exploring the mode-of-action of bioactive compounds by chemical-genetic profiling in yeast. Cell 126: 611-6. PMID: 16901791
Jin, Z., Homola, E.M., Goldbach, P., Choi, Y.H., Brill, J. A. and Campbell, S.D. (2005) Drosophila Myt1 is a Cdk1 inhibitory kinase that regulates multiple aspects of cell cycle behavior during gametogenesis. Development 132: 4075-4085. PMID: 16107480
Wong, R., Hadjiyanni, I., Wei , H.-C., Polevoy, G., McBride, R., Sem, K.-P. and Brill, J.A. (2005) PIP2 hydrolysis and calcium release are required for cytokinesis in Drosophila spermatocytes. Current Biol 15: 1401-1406. PMID: 16085493 [Featured in Nature "Research Highlights."]
Saul, D., Fabian, L., Forer, A. and Brill, J. A. (2004) Continuous phosphatidylinositol metabolism is required for cleavage of crane-fly spermatocytes. J Cell Sci 117: 3887-3896. PMID: 15265984 [Cover article. Cover illustration included in textbook (Cell and Molecular Biology, 5th edition, by G. Karp).]
Wei, H.-C., Sanny, J., Shu, H., Baillie, D. L., Brill, J. A., Price, J. V. and Harden, N. (2003) The Sac1 lipid phosphatase regulates cell shape change and the JNK cascade during dorsal closure in Drosophila. Current Biol 13: 1882-1887. PMID: 14588244
Xu, H., Brill, J. A., Hsien, J., McBride, R., Boulianne, G. L. and Trimble, W. S. (2002) Syntaxin 5 is required for cytokinesis and spermatid differentiation in Drosophila. Dev Biol 251: 294-306. PMID: 12435359
Brill, J. A., Hime, G. R., Scharer-Schuksz, M. and Fuller, M. T. (2000) A phospholipid kinase regulates actin organization and intercellular bridge formation during germline cytokinesis. Development 127: 3855-3864. PMID: 10934029 [Cover article.]
Hime, G. R,* Brill, J. A.* and Fuller, M. T. (1996) Assembly of ring canals in the male germline from structural components of the contractile ring. J Cell Sci 109: 2779-2788. *Co-first authors. PMID: 9013326 [Cover article.]