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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI066538-03
Application #
7226286
Study Section
Special Emphasis Panel (ZRG1-F13 (20))
Program Officer
Mcgugan, Glen C
Project Start
2005-06-01
Project End
2008-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
3
Fiscal Year
2007
Total Cost
$50,428
Indirect Cost
Name
Stanford University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Zeiner, Gusti M; Boothroyd, John C (2010) Use of two novel approaches to discriminate between closely related host microRNAs that are manipulated by Toxoplasma gondii during infection. RNA 16:1268-74
Zeiner, Gusti M; Norman, Kara L; Thomson, J Michael et al. (2010) Toxoplasma gondii infection specifically increases the levels of key host microRNAs. PLoS One 5:e8742
Zeiner, Gusti M; Cleary, Michael D; Fouts, Ashley E et al. (2008) RNA analysis by biosynthetic tagging using 4-thiouracil and uracil phosphoribosyltransferase. Methods Mol Biol 419:135-46