SYNTHESIS OF N-ACETYLGALACTOSAMINE IN ENCYSTING GIARDIA

描述(改编自《应用摘要》)：贾第鞭毛虫是主要 人类传染性水源性肠道疾病的原因。不过， 人们对贾第虫的基本生物学知之甚少，特别是它的 囊化机制，这是寄生虫从 一台主机到另一台主机。因此，该项目的总体目标是 详细介绍包囊合成途径(S) 壁特异性氨基己糖，N-乙酰半乳糖胺(GalNAc)，需要 并在贾第鞭毛虫包囊期间被特别诱导。这一总体目标 将通过完成以下具体目标来实现：1) 用同位素确定GalNAc合成的可能途径 已知GalNAc标记体外包囊贾第鞭毛虫滋养体 先驱物。2)关键的GalNAc合成酶的表征 关于它们的动力学、底物专一性和对已知的敏感性 抑制剂。 该项目的完成应为后续工作提供重要信息 以下是长期目标：1)了解 包膜及其在分子水平上的调控，2)开发新的 以GalNAc合成或其他包囊途径为靶点的化疗，以及 3)改进检测人体贾第鞭毛虫的诊断方法 环境样本。

DESCRIPTION (Adapted from the Applicat's Abstract): Giardia is the major cause of infectious waterborne intestinal disease in humans. Nevertheless, little is known about the basic biology of Giardia, specifically, its mechanism of encystment, which is required for parasite transmission from one host to the next. Thus, the overall objective of this project is to provide detailed knowledge on pathway(s) of synthesis of the cyst wall-specific amino hexose, N-acetylgalactosamine (GalNAc), required for and specifically induced during Giardia encystment. This overall objective will be accomplished by completing the following specific aims: 1) Determination of the possible pathways of GalNAc synthesis using isotopic labeling of in vitro encysting Giardia trophozoites with known GalNAc precursors. 2) Characterization of key GalNAc synthetic enzymes with respect to their kinetics, substrate specificity, and sensitivity to known inhibitors. Completion of this project should give important information for pursuing the following long range goals: 1) to understand the mechanism of encystment and its regulation at the molecular level, 2) to develop new chemotherapy targeting GalNAc synthesis or other encystment pathways, and 3) to improve diagnostic methods for detecting Giardia in human and environmental samples.