The College of Natural Sciences at The University of Texas at Austin
The University of Texas at Austin

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Paul Macdonald
Mr. and Mrs. Robert P. Doherty, Jr. Regents Chair In Molecular Biology

Main Office: MBB 2.422A
Phone: 232-6292

Alternate Office: MBB 2.422
Alt. Phone: 232-6294

Mailing Address
The University of Texas at Austin - ICMB
1 University Station A4800
2500 Speedway
Austin ,TX 78712-0159

Paul Macdonald

Research Summary

Regulation of gene expression at the post-transcriptional level has long been recognized for its essential role in early development, and has more recently emerged as a widespread phenomenon affecting the majority of mRNAs. We study several forms of control in a setting - Drosophila oogenesis - where this regulation is extensive and crucial for the patterning processes that define the body plan of the embryo. A combination of mRNA localization, translational regulation, and protein anchoring act to deploy several molecules at specific positions within the egg, where they act as localized determinants of cell fate. Our work on mRNA localization included the initial discovery of mRNA localization signals, and the identification of the factors that recognize the signals. The main focus of the lab now is on translational regulation of the localized mRNAs, using the oskar mRNA as a model. The oskar mRNA must be translationally repressed prior to its localization at the posterior pole of the oocyte, and then selectively activated at that site. We have identified cis-acting elements and trans-acting factors involved in repression and activation. Using a combination of genetics, biochemistry, and cell and molecular biological approaches we are trying to explain the mechanisms of repression and activation, and how they are coordinated with mRNA localization. A surprising outcome of our work has been the discovery that translational control can be exerted in trans: the control elements on one molecule of oskar mRNA can influence the translation of other molecules of oskar mRNA. This property is likely to be dependent on assembly of oskar transcripts in large particles, with intermolecular interactions within the particles allowing the regulation in trans. Understanding trans regulation is another goal of the lab.



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