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About Sickkids
About SickKids

Julie Brill, PhD

Research Institute
Senior Scientist
Cell Biology

University of Toronto
Director
Collaborative Program in Developmental Biology

Professor
Department of Molecular Genetics

Member
Institute of Medical Science


Phone: 416-813-8863
Fax: 416-813-8456
e-mail: julie.brill@sickkids.ca
Alternate Contact: Mary Ann Gueco (Secretary)
Alternate Phone: (416) 813-7654 x303045

Brief Biography

Dr. Julie Brill graduated with Distinction in Biology from Swarthmore College. She received her PhD in Biology from M.I.T. As a Postdoctoral Fellow at Stanford School of Medicine and a Visiting Postdoc at University of Washington, she discovered a phosphatidylinositol (PI) 4-kinase (PI4KIIIβ, or Fwd) required for cytokinesis in Drosophila melanogaster spermatocytes. This discovery led Dr. Brill to further investigate PI4Ks and PI phosphates (PIPs) in her own lab, where she and her colleagues have uncovered novel roles for PIPs and PIP regulatory enzymes in cytokinesis, sperm tail formation, maintenance of cortical integrity, cell polarization and biogenesis of regulated secretory granules.

Academic Background

  • BA with Distinction in Biology, Swarthmore College, Swarthmore, PA
  • PhD in Biology with Dr. G. R. Fink, Massachusetts Institute of Technology, Cambridge, MA
  • Postdoctoral training at Stanford University School of Medicine with Dr. M. T. Fuller and at University of Washington with Dr. B. T. Wakimoto

Awards and Honours

  • Recipient of National Institutes of Health National Research Scholarship Award, Leukemia & Lymphoma Society Special Fellowship
  • Elected 2015 Fellow of the American Association for the Advancement of Science (AAAS)

Research Interests

  • Cytokinesis
  • Differentiation
  • Spermatogenesis
  • Cell morphogenesis
  • Organelle biogenesis
  • Membrane trafficking
  • Cytoskeletal organization
  • Phosphoinositide signaling
  • Post-transcriptional regulation

Research Activities

Phosphatidylinositol (PI) phosphates (PIPs) are membrane lipids with crucial 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 development. Our 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. In addition, we have generated transgenic flies expressing fluorescent protein fusions that enable 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 mechanisms by which PI 4-phosphate (PI4P), PI 4,5-bisphosphate (PIP2) and PIP pathway enzymes control cytokinesis, gametogenesis, cell morphogenesis and organelle biogenesis. Current studies focus on 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. Because PIPs and PIP regulatory enzymes are found in all eukaryotes, our research will identify conserved cellular mechanisms fundamental to human development and disease.

External Funding

  • Canadian Institutes of Health Research
  • Natural Sciences & Engineering Research Council

Publications

For a full list of Dr. Brill’s publications, see PubMed

Invited Reviews

Brill, J. A., Yildirim, S. and Fabian, L. (2016) Phosphoinositide signaling in sperm development. Semin Cell Dev Biol 59: 2-9. PMID: 27321976 [Cover article]

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
Fabian, L. and Brill, J. A. (2012) Drosophila spermiogenesis: Big things come from little packages. Spermatogenesis 2 (3): 197-212. PMID: 23087837. [Cover article.]

Brill, J. A., Wong, R. and Wilde, A. (2011) Phosphoinositide function in cytokinesis. Current Biol 21: R930-R934. PMID: 22115464
 

Research Articles

Giansanti, M. G., Vanderleest, T. E., Jewett, C. E., Sechi, S., Frappaolo, A., Fabian, L., Robinett, C. C., Brill, J. A., Loerke, D., Fuller, M. T. and Blankenship, J. T. (2015) Exocyst-Dependent Membrane Addition Is Required for Anaphase Cell Elongation and Cytokinesis in Drosophila. PLoS Genetics 11: e1005632. PMID: 26528720

Wen, J., Duan, H., Bejarano, F., Okamura, K., Fabian, L., Brill, J. A., Bortolamiol-Becet, D., Martin, R., Ruby, J. G. and Lai, E. C. (2015) Adaptive regulation of testis gene expression and control of male fertility by the Drosophila hairpin RNA pathway. Mol Cell 57: 1-14. PMID: 25544562

Sing, A., Tsatskis, Y., Fabian, L., Hester, I., Rosenfeld, R., Bietenhader, M., Shanbhag, R., Jurisicova, A., Brill, J. A., McQuibban, G. A. and McNeill, H. (2014) The atypical cadherin fat directly regulates mitochondrial function and metabolic state. Cell 158: 1293-1308. PMID: 25215488 [Featured in Leading Edge Preview, Cell.]

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 127: 3745-56. PMID: 25002402  

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

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 proteins 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 phosphatidylinositol 4-kinases control lysosomal delivery of the Gaucher disease enzyme, β-glucocerebrosidase. Mol Biol Cell 23: 1533-45. PMID: 22337770

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) Phosphatidylinositol 4,5-bisphosphate directs spermatid cell polarity and exocyst localization in Drosophila. Mol Biol Cell 21: 1546-1555. PMID: 20237161  [Cover article. Ranked as Exceptional 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 four wheel drive in localizing Rab11 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 germ line from structural components of the contractile ring. J Cell Sci 109: 2779-2788. *Co-first authors. PMID: 9013326 [Cover article.]