Paul M MacdonaldProfessor
Mr. and Mrs. Robert P. Doherty, Jr. Regents Chair in Molecular BiologyHow mRNAs become localized within cells, and how their translation is firstname.lastname@example.org
The University of Texas at Austin
Molecular Biosciences, College of Natural Sciences
100 West 24th Street
Austin, TX 78712
A key challenge in biology is understanding how proteins are directed to the subcellular domains in which they function. We use Drosophila to address this question, focusing on factors localized to restricted regions of the oocyte, where they initiate events that specify the spatial organization of the embryo. The large size of the oocyte, together with the wealth of powerful genetic approaches using Drosophila, offers many advantages for mechanistic studies.
Our work has provided basic insights into the roles of mRNA localization and translational regulation in controlling subcellular protein localization. Current projects address the mechanisms of translational repression and activation, and how translational activation is coordinated with mRNA localization to achieve highly restricted protein distributions.
In addition, we are studying a remarkable phenomenon we recently discovered: some translational control elements can act in trans, with the regulatory elements within one mRNA affecting the expression of other mRNAs. We hypothesize that regulation in trans is made possible by assembly of mRNAs into particles, in which close proximity allows communication between mRNAs.
2012 Reveal B, Garcia C, Ellington A and Macdonald PM, Multiple RNA binding domains of Bru confer recognition of diverse binding sites for translational repression. , RNA Biology 8: 1047-60
2011 Macdonald PM, mRNA localization: assembly of transport complexes and their incorporation into particles, Curr Opin Genet Dev. 21: 407-413
2010 Reveal B, Yan N, Snee MJ, Pai CI, Gim Y, Macdonald PM, BREs mediate both repression and activation of oskar mRNA translation and act in trans, Developmental Cell 18: 496-502
2009 Lyon AM, Reveal BS, Macdonald PM, Hoffman DW, Bruno protein contains an expanded RNA recognition motif, Biochemistry 48: 12202-12
2009 Reich J, Snee MJ, Macdonald PM, miRNA-dependent translational repression in the Drosophila ovary., PLoS One 4: e4669
2009 Snee MJ, Macdonald PM, Dynamic organization and plasticity of sponge bodies., Dev. Dynamics 238: 918-920
2009 Snee MJ, Macdonald PM, Bicaudal C and trailer hitch have similar roles in gurken mRNA localization and cytoskeletal organization, Dev Biol. 328: 434-444
2008 Snee M, Benz D, Jen J, Macdonald PM., Two distinct domains of Bruno bind specifically to the oskar mRNA, RNA Biol 5: 1-9
2007 Jones JR, Macdonald PM, Oskar controls morphology of polar granules and nuclear bodies in Drosophila, Development 134: 233-236
2006 Geng C, Macdonald PM, Imp associates with Squid and Hrp48 and contributes to localized expression of gurken, Molecular and Cellular Biology 26: 9508-9516