ANALYSIS OF PROGRAMMED CELL DEATH IN FILAMENTOUS FUNGI

丝状真菌细胞程序性死亡的分析

• 批准号: 6628850
• 负责人: N Louise GLASS
• 金额: $ 27.56万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6628850
• 关键词: Neurospora; apoptosis; cell cycle; fungal genetics; fungal proteins; genetic regulation; microorganism culture; microorganism growth; protein localization

The aim of this grant proposal is to genetically and molecularly characterize vegetative incompatibility in the filamentous fungus, Neurospora crass. Vegetative incompatibility is a type of programmed cell death that can prevent transfer of infectious agents such as mycoviruses, throughout a fungal population. Vegetative incompatibility is universal in filamentous fungi, but is apparently absent from S. cerevisiae and S. pombe, presumably because of their unicellular or pseudohyphal growth habit. Unlike other filamentous fungi, N. crassa has a genetically well-defined vegetative incompatibility system (het loci) and both genetic and molecular tools are available. We have previously cloned and characterized three het loci, mating-type, het-c and het-6. This grant proposal describes experiments to elucidate the mechanism of vegetative incompatibility mediated by het-c in N. crassa. Our hypothesis concerning the basis of het-c mediated vegetative incompatibility states that the co-localization of alternative het-c polypeptides in a common cytoplasm triggers death by interference with the regulation of mitosis. We believe that an analysis of vegetative incompatibility in N. crassa will reveal links between cell cycle regulation and induction into programmed cell death in a simple eukaryote. The Specific Aims of this grant proposal are 1. To delineate the requirements for het-c allelic specificity, 2. Localize HET-C within the cell during growth and during programmed cell death, 3. To dissect the mechanism of vegetative incompatibility using both biochemical and genetic analyses. The analysis of vegetative incompatibility using both biochemical and genetic analyses. The analysis of vegetative incompatibility in filamentous fungi will provide information on the evolution of programmed cell death and may uncover mechanisms of cell cycle regulation and cell death that are not accessible by other means. Understanding the pathway of programmed cell death in filamentous fungi may provide unique targets for the development of fungal-specific drugs to combat human diseases caused by filamentous fungi.

这项资助计划的目的是从遗传学和分子生物学的角度研究丝状真菌粗糙脉孢菌的营养体不相容性。营养体不亲和性是一种程序性细胞死亡，可以防止感染因子如真菌病毒在整个真菌种群中的转移。营养体不亲和性在丝状真菌中普遍存在，但在S.酿酒酵母和酿酒酵母。pombe，大概是因为它们的单细胞或假菌丝生长习惯。与其他丝状真菌不同，N. crassa具有遗传上明确的营养体不亲和性系统（het基因座），并且遗传和分子工具都可用。我们以前已经克隆和表征三个het基因座，交配型，het-c和het-6。本基金申请描述了阐明在N.粗鲁。我们关于het-c介导的营养体不亲和性的基础的假设指出，在共同的细胞质中的替代性het-c多肽的共定位通过干扰有丝分裂的调节而触发死亡。我们认为，营养体不亲和性的分析，N。crassa将揭示细胞周期调节和诱导简单真核生物程序性细胞死亡之间的联系。本基金的具体目标是1。描述het-c等位基因特异性的要求，2。在生长期间和程序性细胞死亡期间将HET-C定位在细胞内，3.从生化和遗传两方面剖析营养体不亲和性的机理。营养体不亲和性的生化和遗传分析。丝状真菌营养体不相容性的分析将提供有关程序性细胞死亡的进化信息，并可能揭示细胞周期调控和细胞死亡的机制，这是无法通过其他手段。了解丝状真菌中程序性细胞死亡的途径可能为开发真菌特异性药物以对抗丝状真菌引起的人类疾病提供独特的靶点。