With Drosophila as an experimental system we can use a wide variety of methods, including both forward and reverse genetics as well as biochemical and imaging approaches. Drosophila research has a rich history at the University of Texas at Austin (the picture above is of a stone carving on the former Experimental Sciences Building), with important early contributions from Muller, Painter, and Patterson.
Recent insights from our characterization of cis-acting elements in the osk RNA include the surprising discovery that regulatory elements in one molecule of osk mRNA can influence repression and activation of translation of another molecule of osk mRNA. This effect is dependent on assembly of osk mRNAs into cytoplasmic particles. Presumably, the close proximity of different osk mRNA molecules in the particles enables this phenomenon of 'regulation in trans'.
We also recently found that cis-acting elements responsible for the initial step in localization of osk mRNA are, and must be, individually weak, even though this step of localization is efficient and essential. Our evidence strongly suggests that these localization signals must be weak to allow transfer of osk mRNA to the machinery that directs the subsequent steps in localization.
We have studied the molecular mechanisms responsible for setting up the body plan of the Drosophila embryo. This patterning process relies on deployment of several key proteins at specific locations in the oocyte and embryo. Deployment of the proteins is acheived by a combination of mechanisms:
- mRNA localization
- repression and activation of the translation of the localized mRNAs
- anchoring of the proteins encoded by the localized mRNAs
Projects in the lab have addressed these mechanisms, primarily localization of bicoid mRNA, and localization and translational regulation of oskar mRNA.
During this work we have often focused on the cis-acting sequences present in mRNAs that direct their localization and translational status, and the proteins that bind these sequences. We identify, map and characterize the cis-acting elements to learn about their roles. Knowing that a certain cis-acting element performs an important and interesting function, we then look for the protein that binds the element to mediate this function. Through genetic and biochemical characterization of such a binding protein we can determine if it does indeed mediate the function of the cis-acting element, and begin to understand how it acts.