I. Identification of mRNA decay networks in the nervous system We have developed a novel technique that allows measurement of mRNA decay in the nervous system of Drosophila. This technique provides the foundation for a systems-level approach that we are using to construct a neural development mRNA decay network comprised of the following information:genome-wide mRNA decay rates in neural cells of intact embryos, the cis-elements that target mRNAs for decay, the trans-acting RNA-binding proteins (RBPs) and microRNAs that recognize these cis-elements, and the spatial dynamics of mRNA-RBP interactions within neurons. Our long-term goal is to generate a comprehensive and predictive map of neural mRNA decay dynamics, thus filling a significant gap in current models of gene expression during neural development. II. Capturing physiological maps of neural gene expression Understanding brain function requires maps of neural connections and complementary measurements of neural activity. Gene expression is an essential component of neural activity: neurons change their gene expression in response to different stimuli and these changes have short-term and long-term effects on brain function. Identification of gene expression patterns in intact brains presents significant technical challenges. We are developing an improved RNA-tagging and purification technique (similar to TU-tagging) that will allow us to capture "snapshots" of gene expression in specific populations of neurons. Our current focus is on developing the necessary tools and applying this technique to the study of gene expression following ethanol exposure (in collaboration with Professor Fred Wolf at UC Merced). This work is supported by a grant from Cal-BRAIN.

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