SYNTHESIS OF N-ACETYLGALACTOSAMINE IN ENCYSTING GIARDIA

描述（改编自应用摘要）：贾第虫是主要的 人类传染性水传播肠道疾病的原因。 然而，尽管如此， 人们对贾第虫的基础生物学知之甚少，具体来说，它的 包囊形成机制，这是寄生虫传播所必需的， 一个接一个 因此，本项目的总体目标是 提供有关包囊合成途径的详细知识 壁特异性氨基己糖，N-乙酰半乳糖胺（GalNAc）， 并且在贾第虫包囊形成期间被特异性地诱导。 这一总体目标范围 将通过完成以下具体目标来实现：1） 利用同位素技术确定GalNAc合成的可能途径 用已知的GalNAc标记体外成囊贾第虫滋养体 前体 2)用半乳糖醛酸合成酶表征关键的半乳糖醛酸合成酶 就其动力学、底物特异性和对已知的 抑制剂的 该项目的完成应提供重要的信息，为追求 长期目标如下：1）了解 在分子水平上研究包囊形成及其调控，2）开发新的 靶向GalNAc合成或其他包囊形成途径的化疗，和 3)改进检测人体贾第虫的诊断方法， 环境样品。

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.