NOTE:
I'm looking for motivated graduate students for 2004. If interested, please contact me....
NOTE:
I'm looking for motivated graduate students for 2004.
If interested, please contact me....
Research Interests:
How does a migrating cell know in which direction to turn? What steers an axon along the correct path during outgrowth? How does a cell or growth cone know when it has reached its final destination? These are the questions my laboratory is interested in. We have chosen the soil nematode Caenorhabditis elegans as a model system because of its powerful genetics and transparency, which allows for individual cells and their processes to be viewed by light microscopy.
Our starting point has been the study of the unc-53 gene, which is required for the directional guidance and extension of a subset of cells: the mechanosensory neurons, the excretory canals and the sex muscles in the anterior-posterior (longitudinal) axis of the worm. In vitro, UNC-53 protein binds actin and the SH2SH3 adapter protein SEM-5/GRB2, which is a key component of various receptor tyrosine kinase (RTK) signaling pathways. While extension of muscle cells in unc-53 mutants is reduced, overexpression of UNC-53 in muscle cells results in increased extension of these cells during embryogenesis. Together, the biochemical and genetic evidence suggest that UNC-53 may act to interpret or relay a signal from the cell surface to the actin cortex to promote a cytoskeletal rearrangement that favours outgrowth in a particular direction.
We are utilizing two basic approaches to identify additional molecules that are involved in pathfinding. The first approach utilizes genetic screens to identify mutants with defects in steering and outgrowth of the excretory canals and/or the mechanosensory neurons. The excretory cell is an excellent model growth cone to use in this type of analysis because the cell body is located in the anterior end of the animal and extends two short processes anteriorly and two long canals posteriorly along the length of the animal. This bi-directional and short vs. long trajectory allows us to select for mutations that specifically affect only certain aspects of longitudinal pathfinding. The second approach utilizes protein-protein interactions to identify interacting cell guidance molecules. The combination of these approaches should help to elucidate the molecules and processes which control the guidance of migrating or outgrowing cells.
Last updated 10/31/2003