Abstract

The overall objective is to elucidate the mechanisms which regulate the expression of variant surface glycoprotein (VSG) genes in African trypanosomes. The immediate objectives are to characterize the molecular events that mediate antigenic switching (variation) and VSG production during the life cycle. Experiments are proposed to: 1. Identify and characterize telomeric regions that are relevant to the control of VSG gene expression. These experiments are designed to elucidate the processes of VSG gene duplication and control of VSG gene expression. 2. Characterize intrachromasomal VSG genes and their flanking sequences to elucidate the duplicative (ELC) mechanism of VSG gene expression and antigenic diversity. 3. Characterize the unit of VSG gene expression and transcriptional changes associated with changes in VSG gene expression. 4. Identify the molecular mediators of antigenic variation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI017375-08
Application #
3127192
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1982-02-01
Project End
1993-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Seattle Biomedical Research Institute
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Saxena, Alka; Worthey, Elizabeth A; Yan, Shaofeng et al. (2003) Evaluation of differential gene expression in Leishmania major Friedlin procyclics and metacyclics using DNA microarray analysis. Mol Biochem Parasitol 129:103-14
Dole, Vandana S; Myler, Peter J; Stuart, Kenneth D et al. (2002) Expression of biopterin transporter (BT1) protein in Leishmania. FEMS Microbiol Lett 208:89-91
Yan, Shaofeng; Martinez-Calvillo, Santiago; Schnaufer, Achim et al. (2002) A low-background inducible promoter system in Leishmania donovani. Mol Biochem Parasitol 119:217-23
Yan, S; Myler, P J; Stuart, K (2001) Tetracycline regulated gene expression in Leishmania donovani. Mol Biochem Parasitol 112:61-9
Sunkin, S M; McDonagh, P; Cunningham, M L et al. (2001) Conservation of the LD1 region in Leishmania includes DNA implicated in LD1 amplification. Mol Biochem Parasitol 113:315-21
Dole, V S; Raj, V S; Ghosh, A et al. (2000) Immunization with recombinant LD1 antigens protects against experimental leishmaniasis. Vaccine 19:423-30
Chiurillo, M A; Beck, A E; Devos, T et al. (2000) Cloning and characterization of Leishmania donovani telomeres. Exp Parasitol 94:248-58
Sunkin, S M; Kiser, P; Myler, P J et al. (2000) The size difference between leishmania major friedlin chromosome one homologues is localized to sub-telomeric repeats at one chromosomal end. Mol Biochem Parasitol 109:15-Jan
Ghosh, A; Madhubala, R; Myler, P J et al. (1999) Leishmania donovani: characterization and expression of ORFF, a gene amplified from the LDI locus. Exp Parasitol 93:225-30
Lemley, C; Yan, S; Dole, V S et al. (1999) The Leishmania donovani LD1 locus gene ORFG encodes a biopterin transporter (BT1). Mol Biochem Parasitol 104:93-105

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