CELL AND DEVELOPMENTAL BIOLOGY OF TRYPANOSOMATID PARASITES

利什曼原虫是人类特有的细胞内原生动物。 在受感染的患者体内，这种微生物的各种物种栖息在 破坏皮肤或内脏(肝、脾)内的巨噬细胞 和骨髓)。因此，它们要么导致溃疡，要么无法愈合， 毁容的皮肤损害或变性，通常是致命的 内脏疾病。这些疾病折磨着全世界1200多万名患者。 全球热带和新热带地区。我们的研究目的是 了解这一疾病的病理生理机制 有机体。在这方面，基本细胞、分子和发育 利什曼原虫和相关锥虫原虫的生物学 作为人类寄生虫的模型被研究。 这些寄生虫是如何生存、获取营养、繁殖和 在它们的昆虫媒介和哺乳动物宿主中进行区分 了解寄生的基本性质和 这些有机体的进化适应。因为这些寄生虫 直接与主持人互动，了解作曲和 它们的表面膜功能似乎是必不可少的。为此， 寄生虫独特的表膜酶和其他生理活性 相关蛋白质的鉴定和生化特征 确定它们在这些生物生存中的功能作用。 此外，编码这种蛋白质的基因正在被识别和 第一次被描述为，朝着定义他们的表达和 寄生虫生长、分化和发育过程中的调控 发展。此外，涉及靶向删除的实验 这些基因和功能零突变寄生虫的产生是 正在进行中。这些突变体的生存能力将在现场进行测试。 后一项研究的结果应该证明，这些蛋白质 事实上，由这些基因编码的基因对于这些生物的生存是必不可少的 病原体在它们的昆虫媒介和/或哺乳动物宿主中。因此， 目前的研究旨在确定这些人的内在需求 并确定它们的批判性。此外，这些 研究具有实际意义，可以证明这种情况 寄生虫酶是1)鉴定/设计的合乎逻辑的目标 新的化疗药物，2)新诊断药物的发展 针对这些人类病原体的工具和/或潜在的疫苗。

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.