Ellen Gottlieb
| Title: | Assistant Professor |  Video - PC Mac |
| Education: | Ph.D.: 1987, Yale University; A.B.: 1978, Smith College | |
| Postdoc.: | ||
| Research: | RNA trafficking; molecular basis of morphogenesis; cell polarity | |
| Office: | MBB 2.424AA | |
| Phone: | (512) 232-3436 Fax: (512) 471-2149 | |
| E-mail: | egottlieb@mail.utexas.edu | |
| Postal Address: | Institute for Cellular and Molecular Biology The University of Texas at Austin 1 University Sta. A4800 Austin, TX 78712 |
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| Courses taught: | BIO 379J "Regulation of Eukaryotic Gene Expression" BIO 394 "Problems in Microbial Physiology: Regulation of Eukaryotic Gene Expression" |
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The long term goal of our work is to define some of the principles, parameters and players in the exciting new field of RNA trafficking. To do so, we are taking a multidisciplinary approach involving techniques from molecular biology, biochemistry, cell biology and genetics. We make extensive use of synthetic RNA transcripts, cellular extracts and the battery of techniques used to investigate RNA-protein interactions in other steps of RNA biogenesis with clues provided by the genetics of the system. Present efforts include 1)identifying composite discrete cis-acting RNA localization signals; 2) employing these signals to characterize/isolate the trans-acting localization factors which recognize them; 3) examining the regulatory link between RNA localization and other post-transcriptional processes and 4) performing molecular screens to isolate additional localized messages. Our investigation will facilitate definition of the fundamental principles underlying the important process of mRNA trafficking, delineate the specificity used to localize molecules to different regions of a single cell and provide insights into both the molecular basis of morphogenesis and the creation of cell polarity.
The C elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Lin SY, Johnson SM, Abraham M, Vella MC, Pasquinelli A, Gamberi C, Gottlieb E, Slack FJ.
Dev. Cell, 2003 May;4(5):639-50.
ABSTRACT: hunchback regulates the temporal identity of neuroblasts in Drosophila. Here we show that hbl-1, the C. elegans hunchback ortholog, also controls temporal patterning. Furthermore, hbl-1 is a probable target of microRNA regulation through its 3'UTR. hbl-1 loss-of-function causes the precocious expression of adult seam cell fates. This phenotype is similar to loss-of-function of lin-41, a known target of the let-7 microRNA. Like lin-41 mutations, hbl-1 loss-of-function partially suppresses a let-7 mutation. The hbl-1 3'UTR is both necessary and sufficient to downregulate a reporter gene during development, and the let-7 and lin-4 microRNAs are both required for HBL-1/GFP downregulation. Multiple elements in the hbl-1 3'UTR show complementarity to regulatory microRNAs, suggesting that microRNAs directly control hbl-1. MicroRNAs may likewise function to regulate Drosophila hunchback during temporal patterning of the nervous system.
An anterior function for the Drosophila posterior determinant Pumilio. Gamberi C, Peterson DS, He L, Gottlieb E.
Development. 2002 Jun;129(11):2699-710.
ABSTRACT: Bicoid is a key determinant of anterior Drosophila development. We demonstrate that the prototypical Puf protein Pumilio temporally regulates bicoid (bcd) mRNA translation via evolutionarily conserved Nanos response elements (NRE) in its 3'UTR. Disruption of Pumilio-bcd mRNA interaction by either Pumilio or bcd NRE mutations caused delayed bcd mRNA deadenylation and stabilization, resulting in protracted Bicoid protein expression during embryogenesis. Phenotypically, embryos from transgenic mothers that harbor bcd NRE mutations exhibited dominant anterior patterning defects and we discovered similar head defects in embryos from pum(-) mothers. Hence, Pumilio is required for normal anterior development. Since bcd mRNA resides outside the posterior gradient of the canonical partner of Pumilio, Nanos, our data suggest that Pumilio can recruit different partners to specifically regulate distinct mRNAs.
Internally controlled poly(A) tail assay to study gene regulation.Gamberi C, Gottlieb E.
Biotechniques. 2002 Sep;33(3):476, 478, 480.
The 5' Untranslated region of localized maternal messages contains a conserved motif involved in mRNA localization.
Gottlieb, E.
Proceedings of the National Academy Sciences USA 89 (1992): 7164-7168.
ABSTRACT: Messenger RNA (mRNA) localization is emerging as a means of regulating gene expression. This process is operational in fly and frog development, where a subset of maternally inherited RNAs are asymmetrically distributed and thought to impart axial polarity to the embryo. Since most maternal mRNAs are uniformly distributed, an apparatus must exist to recognize and specifically transport these rare localized species. Here I report the identification of a nine-nucleotide motif, YUGUUYCUG, common to the 3' untranslated regions of four sequenced messages of this class: Drosophila bicoid and nanos mRNAs and Xenopus An2 and Vg1 mRNAs. To test the role of this nonamer sequence in the localization process, a Drosophila transient assay has been established. The assay reveals that bicoid mRNA specifically lacking this nonamer is partially mislocalized. In contrast, nonamer deletion is inconsequential to message stability. The existence of specific and general mRNA localization signals is proposed and it is suggested that this conserved motif belongs to the latter category.
Messenger RNA transport and localization.
Gottlieb, E.
Current Opinions in Cell Biology 2 (1990):1080-1086.
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