CELL AND DEVELOPMENTAL BIOLOGY OF TRYPANOSOMATID PARASITES

利什曼原虫是人类的专性细胞内原生动物寄生虫。 在受感染的病人体内，这种生物体的各种物种栖息， 破坏皮肤或内脏（肝、脾）内的巨噬细胞 和骨髓）。因此，他们要么导致溃疡，不愈合， 毁容性皮肤病变或退行性病变，最常见的是致命的 内脏疾病这些疾病折磨着1200多万患者， 热带和新热带地区。我们的研究旨在 了解参与这一病理生理机制， 有机体 在这方面，基本的细胞、分子和发育 利什曼原虫和相关的锥虫原虫的生物学是 作为人类寄生虫的模型进行研究。 这些寄生虫是如何生存，获取营养，繁殖和 在它们的昆虫载体和哺乳动物宿主中的差异是 这些问题对于理解寄生虫的基本本质至关重要， 这些生物的进化适应。因为这些寄生虫 直接与他们的主机，知识的组成， 其表面膜的功能似乎是必不可少的。为此， 独特的寄生虫表面膜酶和其他生理 鉴定相关蛋白质并进行生物化学表征， 决定了它们在这些生物体生存中的功能作用。 此外，正在鉴定编码这些蛋白质的基因， 第一次，为了定义他们的表达， 在寄生虫生长、分化和 发展此外，涉及靶向缺失 这些基因和功能无效突变体寄生虫的产生， 进行中。这些突变体的生存能力将在原位进行测试。 后一项研究的结果应该证明， 事实上，这些基因编码的基因对这些生物的生存至关重要。 病原体在其昆虫载体和/或哺乳动物宿主内。因此 目前的研究旨在确定这些人的内在需求， 生物体，并确定其关键性质。另外这些 这些研究对于证明是否 寄生虫酶是1）鉴定/设计 新的化疗药物，2）开发新的诊断 工具和/或3）针对这些人类病原体的潜在疫苗。

Leishmania are obligate intracellular protozoan parasites of humans. Within infected patients, various species of this organism inhabit and destroy macrophages within the skin or internal organs (liver, spleen and bone marrow). Thus, they cause either ulcerative, nonhealing, disfiguring cutaneous lesions or degenerative and most often fatal visceral disease. These diseases afflict over 12 million patients in the tropics and neo-tropics worldwide. Our studies are aimed at understanding the mechanisms involved in the pathophysiology of this organism. In that regard, the basic cell, molecular and developmental biology of Leishmania and related trypanosomatid protozoa are investigated as models of human parasitism. How these parasites are able to survive, access nutrients, multiply and differentiate within their insect vector and mammalian hosts are questions central to understanding the basic parasitic nature and evolutionary adaptations of these organisms. Since these parasites interact directly with their hosts, knowledge of the composition and functions of their surface membranes seems essential. To that end, unique parasite surface membrane enzymes and other physiologically relevant proteins are identified and biochemically characterized to determine their functional roles in the survival of these organisms. Further, the genes encoding such proteins are being identified and characterized for the first time, toward defining their expression and regulation during course of parasite growth, differentiation and development. Further, experiments involving the targeted-deletion of such genes and the production of functionally null mutant parasites are in progress. The viability of such mutants will be tested in situ. Results of the latter studies should demonstrate whether the proteins encoded by these genes are, in fact, essential for the survival of these pathogens within their insect-vector and/or mammalian hosts. Thus, the current studies are aimed at defining the intrinsic needs of these organisms and determining their critical nature. In addition, these studies are of practical relevance toward demonstrating whether such parasite enzymes are logical targets for 1) the identification/design of new chemotherapeutic drugs, 2) the development of new diagnostic tools and/or 3) potential vaccines against these human pathogens.