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Emily Crane - Graduate Student 131 Koshland Hall Mailing Address: |
| Research Summary |
| In Caenorhabditis elegans, sex is determined by the ratio of X chromosomes to sets of autosomes (X:A ratio). A ratio of 0.5 (1X:2A) specifies male development while a ratio of 1.0 (2X:2A) specifies hermaphrodite development. X signal elements (XSEs) such as sex-1, or autosomal signal elements (ASEs) communicate X or A signal, respectively. In males, ASEs activate the master sex determination gene xol-1 (XO-lethal); while in hermaphrodites, xol-1 is inhibited by the higher dose of XSEs. xol-1 negatively regulates sdc-2, a gene required for the hermaphrodite mode of sex determination and dosage compensation. Dosage compensation is a mechanism employed by organisms that have unequal numbers of sex chromosomes. This process equalizes X chromosome gene expression between the sexes. In C. elegans, dosage compensation is elicited by a multi-subunit complex, the dosage compensation complex (DCC), which is targeted to the X chromosomes in XX hermaphrodites where it reduces X-linked gene expression by half to match that of XO males. While there is much known about the localization and formation of the DCC, its exact mechanism of repression is still being elucidated. We have found a connection between dosage compensation and the small RNA machinery in C. elegans. Evidence exists in many organisms that non-coding RNAs play a role in dosage compensation. For example, Drosophila roX RNA's are essential for dosage compensation and mammals require Xist RNA to silence the X chromosome. We have shown in C. elegans that alg-2, one of the two argonautes that specifically process miRNAs, plays a role in dosage compensation; alg-2 mutants disrupt dosage compensation in sensitized backgrounds. Our analysis also revealed that an alg-2(ok304) mutant sensitized by a weak DCC mutation preferentially upregulates expression of dosage compensated genes on the X-chromosome. This evidence supports a model where ALG-2 processes a miRNA, which then downregulates an inhibitor of dosage compensation. I am currently investigating whether specific miRNAs affect dosage compensation, either through repression of a gene that inhibits dosage compensation, or through a novel mechanism. |
| Publications/Presentations |
| Jacob M Zahn, Rebecca Sonu, Hannes Vogel, Emily Crane, Krystyna Mazan-Mamczarz, Ralph Rabkin, Ron W. Davis, Kevin Becker, Art B. Owen, Stuart K Kim. (2006) Transcriptional Profiling of Aging in Human Muscle Reveals a Common Aging Signature. PLoS Genet 2(7) early online release.
Graham E. J. Rodwell, Rebecca Sonu, Jacob M. Zahn, James Lund, Julie Wilhelmy, Lingli Wang, Wenzhong Xiao, Michael Mindrinos, Emily Crane, Eran Segal, Bryan D. Myers, Ronald W. Davis, John Higgins, Art B. Owen and Stuart K. Kim. (2004) A Transcriptional Profile of Aging in the Human Kidney. PLoS Biology 2(12), 2191. |
| Education |
| 2004 - 2005 Stanford University, Stanford, CA Lab Tech 2000 - 2004 |