白色念珠菌中与形态发生相关的蛋白磷酸酶功能分析

项目名称： 白色念珠菌中与形态发生相关的蛋白磷酸酶功能分析

项目编号： No.31470182

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 桑建利

作者单位： 北京师范大学

项目金额： 82万元

中文摘要： 白色念珠菌是一种常见的条件致病菌，同时也是研究细胞形态发生的模式生物。我们将在白色念珠菌细胞增殖及形态发生研究工作基础上，采用最新构建的带有营养缺陷型标记的白色念珠菌单倍体菌株，敲除已知的蛋白磷酸酶基因，创建基因缺失菌株库。通过对突变菌株多种表型分析，筛选出影响细胞形态发生的关键性蛋白磷酸酶，再经过敲除相同基因的二倍体菌株的表型检测，进一步确定关键性蛋白磷酸酶的类型及其对表型影响的特点。深入分析关键性蛋白磷酸酶缺失菌株中菌丝特异性基因表达，催化亚基与调节亚基之间的相互作用，催化反应底物的功能以及酶发挥作用时与菌丝生长信号转导通路的关联。同时通过动物试验检测菌丝生长受到显著影响的菌株的致病性。这一研究将系统回答蛋白磷酸酶与白色念珠菌菌丝生长的相关性及如何关联，并有助于揭示白色念珠菌的致病机制。

中文关键词： 白色念珠菌；蛋白磷酸酶；形态发生；调控机制

英文摘要： Candida albicans is a common opportunistic pathogen, and it is also a model organism used to study cell morphogenesis. Based on the research work about cell proliferation and morphogenesis of C. albicans, we knocked out the known protein phosphatase genes of the haploid C. albicans screened out recently to construct gene deletion library of C. albicans. According to the analysis of the phenotype of the mutant strains, we screened out the key protein phosphatase that influenced cell morphogenesis. And by knocking out the same genes of diploid strains to detect the phenotype, we further characterized the type of the key protein phosphatase and their impact on phenotype. We conducted in-depth analysis of the expression of the haphae-specific genes in the enzyme deletion strains, the interaction between the enzymes and their regulatory subunits, the function of the catalytic reaction substrates and their relationship with the signal transduction pathway of haphal development. Meanwhile by animal experiments we detected the pathogenicity of the strains that their haphal development was affected. This study will answer how protein phosphatase associate with haphal development of C. albicans, and it will also contribute to revealing the pathogenic mechanism of C. Albican.

英文关键词： Candida albicans;protein phosphatase;morphogenesis;regulation mechanism