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About Sickkids
About SickKids

William Trimble, PhD, FRSC

Research Institute
Head and Senior Scientist
Cell Biology

University of Toronto
Professor
Biochemistry

Professor
Physiology

Chair Positions

Canada Research Chair
Molecular Cell Biology


Phone: 416-813-6889
Fax: 416-813-5028
Email: wtrimble@sickkids.ca
Alternate Contact: Rashna Irani
Alternate Phone: 416-813-5727
Alternate Email: rashna.irani@sickkids.ca

Brief Biography

William Trimble obtained his B.Sc. in microbiology in 1981 and PhD in cancer research in 1987, both at the University of Toronto. He then moved to Stanford University for postdoctoral studies with Dr. Richard Scheller where he identified the VAMP SNARE protein.

In 1990 Trimble returned to the University of Toronto where he established a laboratory as a Scientist within the Centre for Research in Neurodegenerative Diseases. He moved to The Hospital for Sick Children (SickKids) in 1995 and joined the Cell Biology program as a Senior Scientist. Trimble served as Associate Chief of Faculty Development for the Research Institute from 2000 to 2004 and was named the Program Head of the Cell Biology Program in 2006.

Trimble was awarded a Canada Research Chair in Molecular Cell Biology in 2005 and in 2006 was elected as a Fellow of the Royal Society of Canada. He is also a Professor in the Departments of Biochemistry and Physiology at the University of Toronto. Trimble’s current research interests focus on the regulation of membrane fusion in the brain, and the mechanisms controlling cell division in normal and cancer cells.

Research Interests

  • Membrane traffic
  • Neurotransmitter release
  • Secretion
  • Cytokinesis
  • Membrane cytoskeleton
  • Phagocytosis

Research Activities

Research Trimble's laboratory is aimed at understanding the mechanisms that control the fusion of intracellular membranes. Such fusion events are responsible for everything from the secretion of neurotransmitters in the brain, the release of hormones into the bloodstream, the maintenance of organelle structure, cell division and a host of other biological processes.

Specifically, he and his team are examining the SNARE proteins, which are thought to control the docking and fusion of secretory vesicles with the plasma membrane. These proteins, VAMP, syntaxin, and SNAP-23/25, form a stable complex which is disassembled by action of the soluble proteins SNAP and NSF. The assembly and disassembly of this complex is thought to represent the stages of secretory vesicle docking and fusion with the membrane respectively.

In addition, they have found an association between the SNARE proteins and a family of proteins which are thought to control the final step in the cell cycle, cytokinesis. These latter proteins, called septins, are filamentous GTPases.

Current work in the laboratory is aimed at determining the relationship between septins and SNAREs in the brain and how they may modulate neural function. The team is also examining the role of septins and SNAREs in cell division, to understand how they are regulated, to define their role in cytokinesis and to investigate their possible roles in aberrant cell division leading to cancer.

External Funding

  • Canadian Institutes for Health Research
  • Canadian Cancer Society
  • Natural Sciences and Engineering Research Council (NSERC) of Canada

Publications

Kim, MS, CD Froese, MP Estey and WS Trimble (2011) SEPT9 occupies the terminal positions in septin octamers and mediates polymerization-dependent functions in abscission. J. Cell Biol. 195:815-26.

Jaqaman, K, H Kuwata, N Touret, R. Collins, W Trimble, G Danuser and S Grinstein.  (2011) The cytoskeleton reduces the diffusional dimensionality of CD36 promoting its aggregation and signaling. Cell 146:593-606

Estey, MP, C DiCiano-Oliveira, MT Bejide, CD Froese, and WS Trimble (2010) Distinct roles of septins in cytokinesis: SEPT9 regulates exocyst localization during abscission. J. Cell Biol. 191:741-749

Yang, Y-M, M Fedchyshyn, G. Grande, J Aitoubah, CW Tsang, H. Xie, C.A. Ackerley, WS Trimble* and L-Y Wang* (2010) Septins regulate developmental switching from microdomain to nanodomain coupling of Ca2+ influx to neurotransmitter release at a central synapse. Neuron 67:100-115 (*co-corresponding authors).  

Tooley, AJ, J. Gilden, J Jacobelli, P Beemiller, WS Trimble, M Kinoshita and MF Krummel (2009) The septin cytoskeleton is essential for cortical integrity and persistent motility in amoeboid T lymphocytes. Nature Cell Biol. 11:17-26  

Tsang, CW, M Fedchyshyn, J Harrison, H Xie, J Xue, PJ Robinson, L-Y Wang and WS Trimble (2008) Superfluous role of mammalian septins 3 and 5 in neuronal development and synaptic transmission. Mol. Cell. Biol. 28:7012-7029

Huang YW, Yan M, Collins RF, DiCiccio JE, Grinstein S, Trimble WS. (2008) Mammalian septins are required for phagosome formation. Mol. Biol. Cell 19:1717-1726

Joo E, Surka M, Trimble WS. (2007) Mammalian Sept2 is required for scaffolding non-muscle myosin II and its kinases. Developmental Cell 13:677-690.

Trimble WS, Grinstein S. (2007) TB or not TB: is the crown important? Cell 130:12-4.

Steels J, Trimble WS. (2006) Resolving polarized views: septins do the twist. Developmental Cell 11:591-592.

Huynh H, Bottini N, Williams S, Cherepanov V, Musumeci L, Saito K, Bruckner S, Vachon E, Wang X, Kruger J, Chow C-W, Pellecchia M, Monosov E, Greer P, Trimble W, Downey G, Mustelin T. (2004) Control of vesicle fusion by a tyrosine phosphatase. Nature Cell Biol. 6: 831-839.

Surka M, Tsang C, Trimble WS. (2002) The mammalian septin MSF localizes with microtubules and is required for cytokinesis. Mol. Biol. Cell 13: 3532-3545.

Terebiznik M, Vieira O, Marcus S, Slade A, Yip CM, Trimble WS, Meyer T, Finlay BB, Grinstein S. (2002) Elimination of host cell PI(4,5)P2 by the phosphatase SopB/SigD promotes membrane fission during invasion by Salmonella. Nature Cell. Biol. 4:766-773.

Xu H, Boulianne GL, Trimble WS. (2002) Drosophila syntaxin 16 is a Q-SNARE implicated in Golgi dynamics. J. Cell Sci. 115: 4447-4455.

Xu H, Brill JA, Hsien J, Boulianne GL, Trimble WS. (2002) Syntaxin 5 is required for cytokinesis during spermatogenesis in Drosophila. Dev. Biol. 251:294-306.

Dent J, Kato K, Peng X-R, Martinez C, Cattaneo M, Poujol C, Nurden P, Nurden A, Trimble WS, Ware J. (2002) A prototypic platelet septin, CDCrel-1, and its participation in platelet secretion. Proc. Natl. Acad. Sci. USA 99:3064-3069

Peng X-R, Jia Z, Zhang Y, Ware J, Trimble WS. (2002) The Septin CDCrel-1 is Dispensable for normal development and neurotransmitter release. Mol. Cell. Biol. 22: 378-387.

Lu WY, Man H, Trimble WS, MacDonald JH, Wang YT. (2001) Activation of synaptic NMDA receptors induces membrane insertion of AMPA receptors and long-term potentiation in cultured hippocampal neurons. Neuron 29: 243-254.

Stewart BA, Mohtashami M, Trimble WS, Boulianne GL. (2000) Ca2+-cooperativity of synaptic transmission depends on the availability of SNARE proteins. Proc. Natl. Acad. Sci. USA 97:13955-13960.

Bajno L, Peng XR, Schreiber A, Moore HP, Trimble WS, Grinstein S. (2000) Focal secretion of VAMP-3 containing vesicle occurs at the phagosome during phagocytosis. J. Cell Biol. 149: 697-705.

Zhang J, Kong C, Xie H, McPherson PS, Grinstein S, Trimble WS. (1999) Phosphatidylinositol phospholipid binding to the mammalian septin H5 is modulated by GTP. Curr. Biol. 9:1458-1467.

Beites CL, Xie H, Bowser R, Trimble WS. (1999) The septin rCDCrel-1 binds syntaxin and inhibits exocytosis. Nature Neuroscience, 2: 434-9.