Title:
Senior Scientist

Institute:
The Hospital for Sick Children

Department:
Program in Cell Biology

Province:
Ontario

Training:
Postdoctoral fellow, Department of Developmental Biology, Stanford University School of Medicine, Palo Alto, CA, USA
PhD, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
BSc with Distinction in Biology, Swarthmore College, Swarthmore, PA, USA
other (specifiy): Visiting Postdoctoral fellow, Department of Zoology, University of Washington, Seattle, WA, USA

Research interests:
Phosphoinositides, Cytokinesis, Cancer Signaling

Career highlights:
Helped show functional redundancy of two MAP kinases in yeast pheromone signal transduction. This was the first demonstration of the power of yeast genetics to identify redundant pathways and has served as a paradigm for this type of analysis.
Demonstrated that intercellular bridges that connect developing male germ cells arise from stabilization of components of the contractile ring. This helped establish Drosophila spermatocytes as a model for studying mechanisms of animal cell cytokinesis.
Discovered that a lipid kinase (phosphatidylinositol 4-kinase IIIb) is required for Drosophila spermatocyte cytokinesis, an observation that suggested membrane composition is critical for cytokinesis. This idea was further substantiated by the discovery that phosphatidylinositol 4,5-bisphosphate (PIP2) and PIP2 hydrolysis are also required for successful cell cleavage. Indeed, a requirement for PIP2 in cytokinesis has been shown to be conserved in mammalian cells.

Research Projects

Project title:
Identifying the PI 4-kinases that drive oncogenic GOLPH3 signaling in Drosophila

Funding period: 
2011-2013

Program:
Operating Grant (Basic Research)

Summary:
The trillions of cells that make up our bodies are each enclosed in membranes. Surprisingly, the lipid composition of these cellular membranes − that is the nature of the various fats and related substances that make them up − must be precisely regulated to prevent inappropriate cell growth. Indeed, imbalances in the phosphatidylinositol (PI) lipids, a class of regulatory lipids, have been directly implicated in tumor formation in humans. To understand how PI lipids control cell growth, we are studying fruit flies with mutations in key enzymes termed PI 4-kinases (PI4Ks) that control PI lipid production. This allows us to use the powerful genetic tools available in the fly system to teach us about how these enzymes function in complex animals such as humans. Studies outlined in the current application will use fly genetics, molecular biology and specialized microscopy techniques to uncover the roles of PI4Ks in a newly discovered cancer signaling pathway.

CRS publications:

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. DOI: 10.4161/cl.1.2.15512  

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.

Past CRS projects:

2004 Control of cell growth by PI4KIIIa and PI4KIIa in Drosophila.

2006 Control of cell division, cell growth and survival by two novel PI 4-kinases in Drosophila.