The proposed research is to study gene regulation in Trypanosome cruzi, the protozoan parasite which causes Chagas' disease. The long-term objective is to gain an understanding of the molecular mechanisms responsible for regulating the stage-specific expression of the FL-160 surface antigen on T. Cruzi. FL-160 surface proteins are found only on the mammalian trypomastigote form but not the insect epimastigote stage. Understanding the regulation of stage-specific surface proteins will help in understanding the mechanisms of adaptation of the parasite to the mammalian host. Preliminary evidence, presented in this grant. suggests that FL-I 60 stage.specific regulation occurs as a post.transcriptional event, perhaps by differential RNA stability. Transient transfection experiments suggest that a cis-acting element in the 3 untranslated region (UTR) of the FL-160 gene is responsible for the stage-specific regulator.
The Specific aims of this project are to : I) confirm that the cis-acting element in the 3' UTR is responsible for the stage-specific regulation using stable transfection; 2) map the cis-acting regulatory element within the 3' UTR; and 3) test for the presence and characterize trans- acting factors that participate in the regulatory mechanisms. In the future it is hoped that trans-acting genes can be identified that are responsible for regulating stage-specific expression of surface antigens. By altering the function of the trans-acting genes. it may be possible to alter the expression of these surface antigen genes to discover their role in infection and pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI009235-03
Application #
2457668
Study Section
Immunology, Virology, and Pathology Study Section (IVP)
Project Start
1998-02-28
Project End
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195