Research Interests
Our lab studies the fruit fly Drosophila melanogaster to understand the mechanisms that underlie pattern formation and size control in metazoans. The events we study involve post-transcriptional gene regulation mediated by signals in the 3'-untranslated regions (UTRs) of various mRNAs.
Translational regulation is responsible for establishing the posterior part of the embryonic body plan. We have shown that regulation of maternal hunchback (hb) mRNA relies on assembly of a large complex of proteins, nucleated by the binding of Pumilio to sites in the 3' UTR. In collaboration with Thomas Edward and Aneel Aggarwal, we are continuing to explore the structure and function of this complex.
One of the co-factors recruited to hb mRNA by Pumilio is named Nanos. Regulated translation and localization of its mRNA ensures that Nanos protein accumulates only where it is needed, in the posterior of the embryo and the primordial germ cells. We have identified one of the key regulators of nanos mRNA, a site-specific RNA-binding protein named Smaug. Like Pumilio, Smaug appears to work in collaboration with other RNA-bound factors. We are currently using genetic and molecular methods to identify these factors.
Another of the co-factors recruited by Pumilio plays a much broader role in regulating organismal size. Brain Tumor (Brat) originally was described as a tumor suppressor in the CNS. We have shown that Brat can also regulate size in the imaginal discs. Currently, we are investigating the mechanism by which Brat and two related proteins coordinately regulate proliferation, apoptosis, and cellular size to set organismal size.
We also study cell cycle regulation during Drosophila development. Current work is focused in three areas: (1) studies of the mechanism of cell cycle-dependent degradation of the ORC1 replication factor; (2) analysis of the role of E2F in transcription of G2/M regulators; (3) a genomic-wide scan for E2F regulatory targets involved in cell cycle and apoptosis.
Source: Wharton lab webpage
