Tim O'Connor, University of British Columbia
Professor
Zoology
Vancouver, British Columbia
timothy.oconnor@ubc.ca
Office:
(604) 822-2578
(604) 822-9759
Expert In
Bio/Research
Dr. O'Connor's lab is interested in understanding the mechanisms that underlie neuronal growth and guidance during embryonic development. Elucidation of these developmental processes should direct enhanced repair of the injured adult nervous system.
During nervous system development, ner...
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During nervous system development, ner...
Click to Expand >>
Bio/Research
Dr. O'Connor's lab is interested in understanding the mechanisms that underlie neuronal growth and guidance during embryonic development. Elucidation of these developmental processes should direct enhanced repair of the injured adult nervous system.
During nervous system development, nerve processes (axons) extend over relatively large distances before synapsing with their appropriate targets. As an axon extends, the motile tip (the growth cone) contacts a wide variety of cellular surfaces and the many molecules situated on or secreted by these different cells. Despite this, neuronal axons make very few errors as they wire up the nervous system. Of the cues that have been identified that direct neurite growth, little is known about the signalling mechanisms that underlie their guidance function. Using the developing chick embryo and a model invertebrate system, his lab is taking two distinct approaches to determine how neurons are guided to their appropriate targets.
One approach is to isolate and test the function of specific cell surface and extracellular matrix molecules in guiding neurons. Two groups of molecules that we are currently working on include the Semaphorin family of neurite growth inhibitory molecules and extracellular matrix molecules that promote neurite outgrowth. They are using a battery of molecular, biochemical and pharmacological techniques to understand how these molecules have their effects on neurite outgrowth. They have recently found that some forms of Semaphorin may promote rather than inhibit neurite outgrowth. They are currently investigating whether this is a property of the different forms of the Semaphorin molecule or a property of the receptor type that interacts with Semaphorins. A second approach the lab is taking to understand how neurons grow is to determine the intracellular events that are responsible for neurite extension. This involves a number of techniques including videomicroscopy of a single or a few neurons as they grow in the developing embryo. Using a variety of fluorescently tagged molecules, they have described a sequence of cytoskeletal events that occur inside a growth cone as a neuron turns in response to a guidance cue. This sequence of events eventually leads to the selective invasion of microtubules down filopodia or lamellipodia that are in contact with high affinity substrates. They have found that F-actin plays a key and necessary role in directing this selective microtubule invasion. A major aim in the lab is to determine the mechanism by which F-actin plays this crucial role.
Using these approaches, Dr. O'Connor's lab will dissect the series of molecular events (from receptors at the cell surface to the assembly of the neuronal cytoskeleton) that occur during neurite outgrowth. This will lead to the development of improved biochemical and pharmacological approaches encouraging regeneration in the adult central nervous system.
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During nervous system development, nerve processes (axons) extend over relatively large distances before synapsing with their appropriate targets. As an axon extends, the motile tip (the growth cone) contacts a wide variety of cellular surfaces and the many molecules situated on or secreted by these different cells. Despite this, neuronal axons make very few errors as they wire up the nervous system. Of the cues that have been identified that direct neurite growth, little is known about the signalling mechanisms that underlie their guidance function. Using the developing chick embryo and a model invertebrate system, his lab is taking two distinct approaches to determine how neurons are guided to their appropriate targets.
One approach is to isolate and test the function of specific cell surface and extracellular matrix molecules in guiding neurons. Two groups of molecules that we are currently working on include the Semaphorin family of neurite growth inhibitory molecules and extracellular matrix molecules that promote neurite outgrowth. They are using a battery of molecular, biochemical and pharmacological techniques to understand how these molecules have their effects on neurite outgrowth. They have recently found that some forms of Semaphorin may promote rather than inhibit neurite outgrowth. They are currently investigating whether this is a property of the different forms of the Semaphorin molecule or a property of the receptor type that interacts with Semaphorins. A second approach the lab is taking to understand how neurons grow is to determine the intracellular events that are responsible for neurite extension. This involves a number of techniques including videomicroscopy of a single or a few neurons as they grow in the developing embryo. Using a variety of fluorescently tagged molecules, they have described a sequence of cytoskeletal events that occur inside a growth cone as a neuron turns in response to a guidance cue. This sequence of events eventually leads to the selective invasion of microtubules down filopodia or lamellipodia that are in contact with high affinity substrates. They have found that F-actin plays a key and necessary role in directing this selective microtubule invasion. A major aim in the lab is to determine the mechanism by which F-actin plays this crucial role.
Using these approaches, Dr. O'Connor's lab will dissect the series of molecular events (from receptors at the cell surface to the assembly of the neuronal cytoskeleton) that occur during neurite outgrowth. This will lead to the development of improved biochemical and pharmacological approaches encouraging regeneration in the adult central nervous system.
Click to Shrink <<