Pum1对新生隐球菌核内复制的调控研究

项目名称： Pum1对新生隐球菌核内复制的调控研究

项目编号： No.31501008

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 何光军

作者单位： 中国科学院微生物研究所

项目金额： 20万元

中文摘要： 由于在细胞分化、发育和肿瘤发生过程中的重要作用，核内复制作为一种重要的染色体倍化机制在高等真核生物中被深入研究。然而在真菌中，核内复制参与的生物学功能及其分子调控机制所知甚少。在环境致病真菌的模式菌新生隐球菌中，核内复制在α同性生殖和致病性相关的形态分化过程中都扮演了重要的角色，说明其可能作为关键的生物学机制链接了隐球菌的α同性生殖和致病性，然而目前对新生隐球菌核内复制的分子和遗传机制并不清楚。Pum1是新生隐球菌中的多功能调控因子，参与了隐球菌的同性生殖、形态分化和性孢子形成。本项目的预实验结果显示，Pum1在新生隐球菌的核内复制过程中也扮演了重要的调控角色。本项目拟采用生物信息学、遗传学、生物化学和小鼠感染等方法，系统揭示Pum1参与调控新生隐球菌核内复制的关键机制，从分子层面上确立核内复制在链接α同性生殖与致病性相关的形态分化上扮演的关键角色，为全面解析隐球菌的致病机制提供理论基础。

中文关键词： 人类致病真菌；新生隐球菌；有性生殖；泰坦细胞；RNA结合蛋白

英文摘要： Endoreplication by the selective loss of mitotic cyclin-dependent kinase (CDK) activity and bypassing the stage of mitosis in response to certain physiological stresses is one of the causal factors in the development of cancer. In the important human fungal pathogen C. neoformans, endoreplication serves as the core mechanism for diploidization prior to meiosis during α unisexual reproduction, which helps balance adaptive fitness (the production of infectious spores) and lineage benefit (the evolution of virulence and antifungal resistance). On the other hand, endoreplication is engaged in the formation of “Titan cell morphology”, a morphotype closely related to cryptococcal pathogenicity. These results support the idea that endoreplication bridges α unisexual reproduction and pathogenesis in C. neoformans. However, little is known about the molecular basis underlying cryptococcal endoreplication and the key regulatory circuit involved. It is demonstrated that a Pumilio-family protein Pum1 plays a pleiotropic role in the coordinated control of morphogenesis, sexual reproduction and sporulation in C. neoformans. Our preliminary results are indicative of the significant involvement of this regulator in the regulation of endoreplication. The main objectives of this proposal are to explore the signaling components of Pum1 pathway and dissect the regulatory mechanism underpinning its control of endoreplication. The results are expected to provide new insight into the critical biological mechanism in orchestrating the unisexual reproduction and pathogenicity in Cryptococcus neoformans.

英文关键词： human pathogenic fungi;Cryptococcus neoformans;sexual reproduction;Titan cell;RNA binding protein