The overall issue addressed by this proposal is to understand regulatory processes governing stage-specific elaboration of the flagellum in Leishmania mexicana. A profound change in flagellar morphology is one of the features distinguishing the insect and mammalian stages of the human pathogen Leishmania. Despite classical recognition of these changes in flagellar morphology occurring curing the life cycle, very little is known about how the structural components of the flagellum are assembled and disassembled in correspondence with the life cycle. Focusing on the paraflagellar rod, this proposal describes experiments to study the regulatory mechanisms deployed by these parasites to control production and demolition of the flagellum and to understand the role played by this motility organelle in the biology of the organism. We will explore regulation at the level of mRNA production, translation, protein transport to the parasites' biology could reveal new targets for antiparasitic therapies. The functional importance of the PFR coupled with its proven potential as a vaccine candidate justify a more complete characterization of this complex structure.
| Holzer, Timothy R; Mishra, Krishna K; LeBowitz, Jonathan H et al. (2008) Coordinate regulation of a family of promastigote-enriched mRNAs by the 3'UTR PRE element in Leishmania mexicana. Mol Biochem Parasitol 157:54-64 |
| Holzer, Timothy R; McMaster, W R; Forney, James D (2006) Expression profiling by whole-genome interspecies microarray hybridization reveals differential gene expression in procyclic promastigotes, lesion-derived amastigotes, and axenic amastigotes in Leishmania mexicana. Mol Biochem Parasitol 146:198-218 |
