Paul M. Macdonald, Ph.D.

Research

A variety of post-transcriptional control mechanisms operate in early Drosophila development, and some of these play central and essential roles in the deployment of the spatial determinants that control body pattern. These determinants must be restricted to discrete regions of the oocyte or embryo. This restriction is achieved by a combination of mRNA localization, translational repression and activation, and protein anchoring. Projects in the lab have addressed each of these mechanisms, focusing primarily on the localization of bicoid mRNA, and on the localization and translational regulation of oskar mRNA. Current projects continue the work on the post-transcriptional regulation of mRNAs encoding the patterning determinants. We are extending our analysis of the role of Bruno in regulation of oskar and other mRNAs, with an emphasis on the molecular interactions of Bruno with regulatory elements and with other proteins. In another project we are examining the cellular context for the molecular interactions of post-transcriptional regulation. The binding of Bruno to oskar mRNA does not occur in isolation, but takes place in the complex environment of the cytoplasm. There are several classes of large ribonucleoprotein complexes (RNPs) that are enriched in Bruno or other regulatory factors. These include sponge bodies (which are enriched near nuclei), nuage (a perinuclear organelle that may be common to all animal germline cells) and polar granules (which are localized to the posterior pole of the oocyte and contain the determinants for posterior body patterning and germ cell formation). These RNPs are presumed to be important for regulation, but details of their functions remain largely unknown. We are also studying regulation of translation by microRNAs (miRNAs).