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First published online March 4, 2009
doi: 10.1242/10.1242/jcs.050203
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JCS Prize |
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). The $1000 prize is awarded annually to the first author of the paper that is judged by the Editors and Editorial Board to be the best published in the Journal that year. To be considered for the prize, the first author must be a student or a postdoc of no more than 5 years' standing. Jennifer was born in Cromwell, Connecticut, and received her B.S. in Molecular and Cell Biology from the University of Connecticut. As an undergraduate, she performed research in the laboratory of Dr Juliet Lee, where she studied transient increases in intracellular Ca2+ during cell migration. Although she initially planned to attend medical school after graduation, she found cell biology, and specifically the cytoskeleton, fascinating and chose instead to go to graduate school to pursue her research interests.
Jennifer entered the PhD program in Cell and Molecular Biology at the University of Pennsylvania, where she did her dissertation research in the laboratory of Dr Erika Holzbaur. Her pursuits there advanced the recent finding that a mutation in the gene encoding the p150Glued subunit of dynactin (an activator of the microtubule motor, cytoplasmic dynein) caused motor neuron disease in a human kindred (Puls et al., 2003). She found that this mutation causes both a loss of function, as it weakens the association between the polypeptide and microtubules and EB1, and a gain of function, as the mutation causes aberrant aggregation of the polypeptide. Furthermore, she showed that aggregation of the mutant polypeptide causes cell death in neuronal cells, and that this death can be rescued by overexpression of the molecular chaperone Hsp70. These findings resulted in a first-author publication in 2006 in the Journal of Cell Biology (Levy et al., 2006).
After publication of the findings on the human mutation, Jennifer returned to studying cell migration. Several reports have suggested that dynein plays a role in nuclear and centrosomal positioning during cell migration. However, inhibition of dynein after polarization suppresses motility, suggesting that there is an additional role for dynein during persistent cell migration (Dujardin et al., 2003). To elucidate a mechanism for dynein in fibroblast motility, Jennifer used RNAi to knock down the microtubule-binding subunits of dynein and dynactin. Surprisingly, she observed that many cells in the control samples had nuclei that rotated upon stimulation of migration. Although this was itself an interesting finding, Jennifer was excited to see that depletion of microtubules or dynein diminished nuclear rotations and caused the nuclei to mislocalize to the rear of the cell. This, together with the observation that nuclear rotations occur independently of centrosome position, suggests that nucleus-associated dynein molecules `walk' along microtubules to maintain the nucleus in the center of the cell as it translocates forward. This role for dynein in nuclear positioning appears to be independent of an additional role for dynein in maintaining centrosome position during migration (Levy and Holzbaur, 2008).
Jennifer recently took a position as a postdoctoral research scholar in the laboratory of Dr Kevin Campbell at the Howard Hughes Medical Institute and the University of Iowa Roy J. and Lucille A. Carver College of Medicine, where she will study the cell biology of the dystroglycan-dystrophin complex.
References
Dujardin, D. L., Barnhart, L. E., Stehman, S. A., Gomes, E. R., Gundersen, G. G. and Vallee, R. B. (2003). A role for cytoplasmic dynein and LIS1 in directed cell movement. J. Cell Biol. 163, 1205-1211.
Levy, J. R. and Holzbaur, E. L. (2008). Dynein drives nuclear rotation during forward progression of motile fibroblasts. J. Cell Sci. 121, 3187-3195.
Levy, J. R., Sumner, C. J., Caviston, J. P., Tokito, M. K., Ranganathan, S., Ligon, L. A., Wallace, K. E., LaMonte, B. H., Harmison, G. G., Puls, I. et al. (2006). A motor neuron disease-associated mutation in p150Glued perturbs dynactin function and induces protein aggregation. J. Cell Biol. 172, 733-745.
Puls, I., Jonnakuty, C., LaMonte, B. H., Holzbaur, E. L., Tokito, M., Mann, E., Floeter, M. K., Bidus, K., Drayna, D., Oh, S. J. et al. (2003). Mutant dynactin in motor neuron disease. Nat. Genet. 33, 455-456.[CrossRef][Medline]
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