一个全新转录因子Msd1调控新生隐球菌细胞形态命运和有性生殖的作用机制研究

新生隐球菌是一种临床上致病性和致死率最高的的病原真菌之一。作为一种酵母-菌丝双态性真菌，新生隐球菌的形态分化与其毒力紧密相关，并且在交配诱导下菌丝形态分化与有性生殖紧密偶联，但其中详细的调控机制并不清楚。前期研究中，我们鉴定一个全新的调控新生隐球菌细胞形态命运的转录因子Msd1，其基因的敲除会导致菌丝形态分化能力急剧降低，并且在交配诱导条件下表现出有性生殖缺陷，因此我们推测Msd1在偶联调控菌丝形态分化和有性生殖过程中发挥了关键作用。本项目拟围绕Msd1如何调控新生隐球菌形态分化和有性生殖展开，通过Msd1遗传学功能的深入探究、靶基因及相互作用蛋白的深入鉴定和功能研究，构建其详细的分子调控网络，从多个层面和维度深入揭示Msd1调控形态分化和有性生殖的分子机制。最后，通过动物实验深入阐明该转录因子对隐球菌致病性和毒力的影响。通过本项目研究的开展，将为寻找安全有效的抗隐球菌策略提供新的思路。

Cryptococcus neoformans is one of the human fungal pathogens with the highest pathogenicity and mortality rate in clinic. As a yeast-hypha dimorphic fungus, the morphogenesis of Cryptococcus neoformans is closely related to its virulence. The yeast-hyph morphological differentiation is closely linked to sexual reproduction under mating induction, but the detailed regulatory mechanism is not clear. In this the study, we identified a novel transcription factor Msd1 that regulates the morphological fate of Cryptococcal cells. The deletion of this gene leads to a sharp decrease in the ability of hyphae morphogenesis and sexual reproduction defects under the mating inducing condition. Therefore, we speculate that Msd1 plays a key role in the coordination of hyphae morphological differentiation and sexual reproduction. This project aims to focus on how Msd1 regulates the morphological differentiation and sexual reproduction in Cryptococcus neoformans. We will construct a detailed molecular regulatory network of Msd1 through in-depth investigation of the genetic function of Msd1 and in-depth identification of its target genes and interacting proteins. Furthermore, the effects of this transcription factor on the pathogenicity and virulence of Cryptococcus will be further investigated through animal experiments. We hope to find new ideas for seeking safe and effective anti-cryptococcus strategies through the work and effort of this project.