Blood borne parasitic diseases are major causes of human morbidity and mortality, particularly in the tropical world. African trypanosomes, the protozoa of the Trypanosoma brucei complex, are such parasites that live extracellularly in the blood and tissue fluids of the vertebrate host, utilizing blood glucose as their sole source of energy eventually leading to hypoglycemia dn disease syndrome known as African sleeping sickness. Mitochondrial biogenesis is an essential part of the digenetic life cycle of this protozoa. These cells suppress their mitochondrial activities when they live in the bloodstream of its mammalian host. During blood-meal, parasites are transferred to the insect gut and they regenerate their mitochondrial activities. Import of a vast majority of nuclear encoded mitochondrial protein is a necessary process for mechanisms in African trypanosomes so as to understand their role sin mitochondrial biogenesis. The initial requirement to accomplish this goal is the isolation and characterization of the trypanosome proteins involved in mitochondrial protein import.
The specific aims of this proposal are: (i) to clone and mitochondrial membrane from T. brucei; (ii) to identify and characterize different cytosolic and mitochondrial chaperone proteins involved in this import process; and (iii) to assess the roles of these cloned proteins in protein important during mitochondrial biogenesis of this parasite. Characterization of the mitochondrial import machinery in this parasite may provide insight into genetic control mechanism in trypanosomes where, in contrast to most eukaryotes, developmental regulation of gene expression is almost entirely post-transcriptional. Understanding of this developmental process will elucidate one of the major aspects of trypanosomal parasitism. This in turn will help us to design rational trypanocidal chemotherapeutic strategies.
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