锥虫蛋白质乳酸化修饰及生物学意义分析

锥虫是一类具有广泛宿主的单细胞鞭毛原虫，流行于世界各大洲。锥虫病仍然是对人畜健康危害巨大的重要人兽共患病之一。由于锥虫具有非常复杂的抗原变异能力，控制或消灭锥虫病的危害主要以研发新的药物和控制媒介昆虫为主。目前治疗人和动物锥虫病的药物非常有限，现有药物的副作用较大，迫切需要研制新型抗锥虫药物用于临床治疗和疫病防控。蛋白质翻译后修饰在生命体中具有十分重要的作用，使蛋白质结构更为复杂,功能更完善,调节更精细,作用更专一。本课题围绕锥虫蛋白质翻译后的修饰及作用机理这一关键科学问题开展研究，在前期锥虫基因组、蛋白质组及大量修饰组学研究的基础上，开展锥虫糖代谢过程中乳酸代谢对锥虫的调控机理研究。重点揭示布什锥虫、伊氏锥虫在发育过程中蛋白质组的乳酸化修饰及对虫体的调控作用。确定乳酸化抑制剂对蛋白质功能及虫体活性的影响，目的是在解析锥虫系统生物学的基础上，确定新的药物靶，为研制新的抗锥虫药物奠定基础。

Trypanosoma species are flagellar protozoan, the causive agents of human and animal trypanosomiases, which are still endemic world-wide and post great threat to human and animal health. Currently, control the impact of the diseases has been relied on the development of novel drugs and insecticides. Due to the sophisticated antigenic variation capacity, it is almost impossible to generate effective vaccines to prevent the diseases. Protein posttranslational modification (PTM) has been realized as the advance regulation of protein structure, subcellular localization and protein function. Here, in the study, we propose, based on our solid knowledge on genome, proteome and PTMome or various protozoan parasites including T. brucei and T. evansi, to systematically dissect the lactylome of both T. brucei and T. evansi. Genome-wide lactylation of the two parasites with a resolution of single protein level will be achieved. And the mechanism of functional regulation of lactates on protein function, especially on the sugar metabolism will be revealed. The data generated from this study will pave a way for the development of novel and urgently-needed drugs for trypanosomiases.