Abstract

Members of the order kinetoplastida are the causative agents of African sleeping sickness (Trypanosoma brucei subspecies), leishmaniasis (Leishmania spp.) and Chagas' disease (Trypanosoma cruzi). There is no vaccine against any of these diseases and current treatments are toxic. The parasite possesses a unique subcellular organelle, the clycosome, which is a distant relative of the peroxisome found in higher eukaryotes. The glycosome houses many of the enzymes of the Embden-Meyerhof pathway of glycolysis, as well as enzymes involved in nucleotide biosynthesis, ether-lipid biosynthesis, Beta-oxidation of fatty acids, purine salvage and pyrimidine biosynthesis. Given the importance of these metabolic pathways to the parasite, the glycosome and its constitution's have been recognized as a possible target for the development of new chemotherapies. Their studies are aimed at understanding glycosomal biogenesis and protein input and the relationship of these processes and the molecules involved to peroxisome biogenesis in the human host.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022635-18
Application #
6748120
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Rogers, Martin J
Project Start
1986-12-01
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2006-05-31
Support Year
18
Fiscal Year
2004
Total Cost
$478,542
Indirect Cost

  Institution

Name
Seattle Biomedical Research Institute
Department
Type
DUNS #
070967955
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Haanstra, Jurgen R; van Tuijl, Arjen; Kessler, Peter et al. (2008) Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes. Proc Natl Acad Sci U S A 105:17718-23
Saveria, Tracy; Halbach, Andre; Erdmann, Ralf et al. (2007) Conservation of PEX19-binding motifs required for protein targeting to mammalian peroxisomal and trypanosome glycosomal membranes. Eukaryot Cell 6:1439-49
Saveria, Tracy; Kessler, Peter; Jensen, Bryan C et al. (2007) Characterization of glycosomal RING finger proteins of trypanosomatids. Exp Parasitol 116:14-24
Kessler, Peter S; Parsons, Marilyn (2005) Probing the role of compartmentation of glycolysis in procyclic form Trypanosoma brucei: RNA interference studies of PEX14, hexokinase, and phosphofructokinase. J Biol Chem 280:9030-6
Banerjee, Sanjiban K; Kessler, Peter S; Saveria, Tracy et al. (2005) Identification of trypanosomatid PEX19: functional characterization reveals impact on cell growth and glycosome size and number. Mol Biochem Parasitol 142:47-55
Furuya, Tetsuya; Kessler, Peter; Jardim, Armando et al. (2002) Glucose is toxic to glycosome-deficient trypanosomes. Proc Natl Acad Sci U S A 99:14177-82
Parsons, M; Furuya, T; Pal, S et al. (2001) Biogenesis and function of peroxisomes and glycosomes. Mol Biochem Parasitol 115:19-28
Mannion-Henderson, J; Flaspohler, J A; Lemley, K R et al. (2000) Isolation and characterization of Leishmania mutants defective in glycosomal protein import. Mol Biochem Parasitol 106:225-37
Flaspohler, J A; Lemley, K; Parsons, M (1999) A dominant negative mutation in the GIM1 gene of Leishmania donovani is responsible for defects in glycosomal protein localization. Mol Biochem Parasitol 99:117-28
Anderson, S A; Carter, V; Hagen, C B et al. (1998) Molecular cloning of the glycosomal malate dehydrogenase of Trypanosoma brucei. Mol Biochem Parasitol 96:185-9

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