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 Dr. 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.

Dr. 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 in my 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, we 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, we 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. We are 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
• National Cancer Institute of Canada
• Natural Sciences and Engineering Research Council
• Heart and Stroke Foundation of Ontario

Publications

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

Wasylnka JA, Bakowski MA, Szeto JRT, Olson MB, Trimble WS, Miller SI, Brumell JH. (2008) SopB activates myosin II to regulate positioning of Salmonella-containing vacuoles. Infect. Immun. 76:2722-2735

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 JD, Estey MP, Froese CD, Renaud D, Pace-Asciak C, Trimble WS. (2007) Septin 12 is a component of the sperm annulus. Cell Motil. Cytoskel. 64:794-807.

Yan M, Grinstein S, Trimble WS. (2007) Coronin function is required for chemotaxis and phagocytosis in human neutrophils. J. Immunol. 178:5769-78.

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

Joo E*, Tsang CW*, Trimble WS. (2005) Septins: traffic control at the cytokinesis intersection. Traffic 6:626-34 *indicates equal contribution.

Yan M, Collins RF, Grinstein S, Trimble WS. (2005) Coronin1 is required for phagocytosis in RAW cells. Mol. Biol. Cell 16: 3077-87.

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.

Collins RF, Schreiber AD, Grinstein S, Trimble WS. (2002) Syntaxin 13 and 7 function at distinct steps during phagocytosis. J. Immunol. 169: 3250-3256.

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.

Gaisano HY, Lutz M, Lesser J, Sheu L, Lynch G, Tang L, Tamori Y, Trimble WS, Salapatek AM. (2001) Supramaximal cholecystokinin displaces Munc18c from the pancreatic acinar basal surface, redirecting apical exocytosis to the basal membrane. J. Clin. Invest. 108: 1597-1611.

Stewart BA, Mohtashami M, Zhou L, Trimble WS, Boulianne GL. (2001) Dominant negative NSF mutants implicate a role for SNARE-dependent transport in Notch signaling at the wing margin in Drosophila. Dev. Biol. 234: 13-23.

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.

Coppolino MG, Kong C, Mohtashami S, Grinstein S, Trimble WS. (2001) Requirement for NSF at different stages of phagocytosis and bacterial invasion. J. Biol.Chem. 276: 4772-4780.

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.

Trimble WS. (1999) Septins: a highly conserved family of membrane-associated GTPases with functions in cell division and beyond. Journal of Membrane Biology, 169: 75-81.

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