类泛素蛋白TgUrm1对弓形虫入侵和增殖的影响及其作用机制

Urm1（Ubiquitin-related modifier-1）是真核生物最古老的类泛素蛋白之一，与细胞的生长发育、硫转运、氮素合成及抗氧化应激等过程密切相关。目前，顶复门原虫中未见相关研究。弓形虫是重要的人兽共患病模式病原，明确Urm1在弓形虫中的作用及其机制是必要的。我们前期的研究发现弓形虫可能存在Urm1类泛素调控系统，但功能未知。为了探究TgUrm1在弓形虫生命活动中的关键作用，本申请项目拟鉴定弓形虫的Urm1类泛素调控系统，并明确TgUrm1对弓形虫入侵、增殖及致病的影响；筛选TgUrm1的泛素激活酶TgUba4，验证TgUrm1与TgUba4的互作修饰关系，初步阐明TgUrm1在弓形虫中发挥功能的分子基础；调控TgUba4的表达，明确TgUba4修饰作用对TgUrm1功能的影响。最终，初步揭示类泛素蛋白TgUrm1在弓形虫中的作用及其机制，为其他顶复门原虫的研究提供参考。

Urm1 (Ubiquitin-related modifier-1) is one of the most primitive ubiquitin-like proteins of eucaryon. Functions are related to the cell growth, sulfur transport, nitrogen synthesis and antioxidant stress. At present, there is no research about Urm1 in apicomplexan parasites. Toxoplasma gondii is a model pathogen of zoonosis, and to analyze the functions and mechanisms of Urm1 in T. gondii is necessary. Our previous studies have showed that Urm1 ubiquitin-like system may exist in Toxoplasma, and the function is unknown. To explore the key role of TgUrm1 in parasites, a program was designed to observe the expression and location of TgUrm1, and analyze the effects of TgUrm1 on parasite invasion, proliferation and pathogenicity; Screening the TgUrm1 activating enzyme TgUba4 , and verifying the modification relationship between TgUrm1 and TgUba4, are necessary works to elucidate the molecular basis of TgUrm1's functions in T. gondii. Regulate the expression of TgUba4 in parasites to further verify the key role of TgUba4 on TgUrm1 functions. Finally, we expect to show the functions and mechanisms of TgUrm1 in T. gondii , and provide references for the research of other apicomplexan parasites.