This research program focuses on the molecular genetics of the parasitic protozoan Leishmania, with particular emphasis on functionally interesting membrane proteins whose expression is regulated during the life cycle of the parasite. In this proposal, several genes for glucose transporter-like proteins that are expressed in a developmentally regulated or stage-specific manner, are studied. An attempt is made to define the biochemical specificity of each transporter by either over- expressing the gene or by targeted gene disruption and studying the subcellular location of each transporter and of several isoforms to determine whether each is targeted to a different membrane domain. A study is also being made of the transcription of one of these genes and attempting to define its promoter, an entity which has not been previously identified for any Leishmania gene. In a new project separate from this proposal, a investigation of a family receptor-adenylate cyclases and their possible roles in signal transduction and in the developmental transformations which occur during the Leishmania life cycle. A long term objective for both of these projects is to understand how the parasite adapts to and survives in the very different environments of its insect vector and its mammalian host. These questions are of fundamental importance to understanding both disease transmission and host colonization for this important pathogen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Modified Research Career Development Award (K04)
Project #
5K04AI001162-03
Application #
2057261
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1993-08-01
Project End
1998-07-31
Budget Start
1995-08-01
Budget End
1996-07-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Seyfang, A; Landfear, S M (2000) Four conserved cytoplasmic sequence motifs are important for transport function of the Leishmania inositol/H(+) symporter. J Biol Chem 275:5687-93
Seyfang, A; Landfear, S M (1999) Substrate depletion upregulates uptake of myo-inositol, glucose and adenosine in Leishmania. Mol Biochem Parasitol 104:121-30
Snapp, E L; Landfear, S M (1999) Characterization of a targeting motif for a flagellar membrane protein in Leishmania enriettii. J Biol Chem 274:29543-8
Vasudevan, G; Carter, N S; Drew, M E et al. (1998) Cloning of Leishmania nucleoside transporter genes by rescue of a transport-deficient mutant. Proc Natl Acad Sci U S A 95:9873-8
Burchmore, R J; Landfear, S M (1998) Differential regulation of multiple glucose transporter genes in Leishmania mexicana. J Biol Chem 273:29118-26
Seyfang, A; Kavanaugh, M P; Landfear, S M (1997) Aspartate 19 and glutamate 121 are critical for transport function of the myo-inositol/H+ symporter from Leishmania donovani. J Biol Chem 272:24210-5
Snapp, E L; Landfear, S M (1997) Cytoskeletal association is important for differential targeting of glucose transporter isoforms in Leishmania. J Cell Biol 139:1775-83
Klamo, E M; Drew, M E; Landfear, S M et al. (1996) Kinetics and stoichiometry of a proton/myo-inositol cotransporter. J Biol Chem 271:14937-43
Drew, M E; Langford, C K; Klamo, E M et al. (1995) Functional expression of a myo-inositol/H+ symporter from Leishmania donovani. Mol Cell Biol 15:5508-15
Langford, C K; Kavanaugh, M P; Stenberg, P E et al. (1995) Functional expression and subcellular localization of a high-Km hexose transporter from Leishmania donovani. Biochemistry 34:11814-21

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