Regulation of mRNA stability during development

Stanford University, Stanford CA

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Abstract

DESCRIPTION (provided by applicant): Toxoplasma gondii infects as many as one in every six people in the United States. Central to the high global prevalence of T. gondii, is its efficient means of infection of a very large number of warm-blooded animal species, and its successful evasion of the host immune response. These two properties of T. gondii are enabled by the tachyzoite to bradyzoite stage-conversion, a key cellular differentiation event that is central to T. gondii persistence and reactivation in human infections. Preliminary experiments implicate mRNA stability as playing a key role in this developmental pathway. The overall goal of this grant is to determine how transcript stability is regulated during tachyzoite to bradyzoite differentiation. To do this we will use a combination of reverse genetic approaches and a recently developed microarray technology that exploits a T. gondii nucleoside salvage pathway to directly assay temporal changes in mRNA stability across the entire transcriptome. T. gondii thus represents an uniquely suited model system to study the role of mRNA stability in eukaryotic developmental biology.