REGULATION OF FLAGELLUM AND PFT IN LEISHMANIA

这项提案涉及的总体问题是了解管理墨西哥利什曼原虫鞭毛特定阶段细化的调控过程。鞭毛形态的深刻变化是区别人类病原体利什曼原虫昆虫和哺乳动物阶段的特征之一。尽管经典地认识到鞭毛形态的这些变化发生在生命周期中，但人们对鞭毛的结构成分如何根据生命周期进行组装和拆卸知之甚少。这项建议以副鞭毛为重点，描述了研究这些寄生虫用来控制鞭毛的产生和破坏的调节机制，以及了解这种运动细胞器在生物体生物学中所起的作用的实验。我们将探索在mRNA产生、翻译、蛋白质转运到寄生虫生物学水平上的调控，以揭示抗寄生虫治疗的新靶点。PFR在功能上的重要性，再加上其作为疫苗候选者的已被证明的潜力，证明了对这种复杂结构的更完整的表征。

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.