TOXOPLASMA BRADYZOITE CYST WALL STRUCTURE/BIOSYNTHESIS

描述：(改编自申请者摘要)弓形虫是一种 先天感染婴儿和患者的重要疾病原因 免疫系统的改变。这种疾病在自然界中是永久存在的 寄生虫的包囊形式，要么是被组织感染的未煮熟的肉 被猫粪便污染的食物或水中的包囊或卵囊。这个 这项提议的总体目的是破译所涉及的分子事件 在这个过程中，重点关注碳水化合物的结构和功能 在囊壁中发现残留物。该提案的具体目标是有针对性的。 A)阐明N-乙酰氨基葡萄糖的结构和生物合成方面 (GlcNAc)和N-乙酰半乳糖胺(GalNAc) 已在囊壁中发现的，以及b)将这些方面与 这些结构在寄生虫分化中的生物学作用。这个 第一个目标是确定GalNAc和GlcNAc的结构和连接 包囊糖偶联物中的残留物及其长期目标 生物合成和确定它们是否作为 细胞壁的合成是分化过程中的一个关键事件。第二 目的是鉴定和纯化发育中的甲壳素合成酶 参与甲壳素生物合成的调节酶。这些研究将 促进制定基因控制的长期目标 鉴定孢子特异基因在分子水平上的分化 编码参与生物合成的发育调节蛋白 细胞壁多糖。最后一个目标是将在 结构和生化水平对红豆杉生长分化的影响 体外寄生虫以及体内寄生虫感染小鼠弓形虫病模型。这个 最终目标是设计战略来遏制差异化，中断 寄生虫的生命周期，并控制疾病的传播。

DESCRIPTION: (Adapted from Applicant's Abstract) Toxoplasma gondii is a significant cause of disease in congenitally infected infants and patients with alterations of the immune system. The disease is perpetuated in nature by encysted forms of the parasite, either as undercooked meat infected with tissue cysts or as oocysts in food or water contaminated with cat excrement. The overall purpose of this proposal is to decipher the molecular events involved in this process, focusing on the structure and function of carbohydrate residues found in the cyst wall. The specific aims of the proposal are directed at a) elucidating structural and biosynthetic aspects of N-acetylglucosameine (GlcNAc) and N-acetylgalactosomaine (GalNAc) containing carbohydrate moieties which have been identified in cyst walls and b) relating these aspects to the biological role of these structures in differentiation of the parasite. The first aim is to determine the structure and linkage of GalNAc and GlcNAc residues in cyst glycoconjugates with the long term objective of studying their biosynthesis and ascertaining whether they serve as precursor moieties for the synthesis of the cell wall which is a key event in differentiation. The second aim is to characterize and purify chitin synthase which is developmentally regulated enzyme involved in the biosynthesis of chitin. These studies will facilitate the long term objective of delineating genetic control for differentiation at the molecular level by identifying cyst specific genes encoding developmentally regulated proteins involved in the biosynthesis of cell wall polysaccharides. The last aim is to relate the findings obtained at the structural and biochemical level to growth and differentiation of the parasite in vitro as well as in vivo in the murine model of toxoplasmosis. The ultimate goal is to design strategies to arrest differentiation, interrupt the life cycle of the parasite, and control spread of disease.