Assembly and Function of the Yeast Spore Wall

性状（申请方提供）：芽殖酵母S.酿酒酵母为真菌细胞壁组装的研究提供了一个强大的，易处理的模型。该基金的重点是阐明孢子壁外两层的结构和组装机制。这两层由多糖壳聚糖和多酚二酪氨酸组成，营养细胞中不存在，使孢子能够抵抗各种环境胁迫。重要的是，虽然壳聚糖和二酪氨酸不存在于芽殖酵母的营养细胞壁中，但它们存在于许多致病真菌如白色念珠菌的细胞壁中。在哺乳动物细胞外基质中没有发现壳聚糖和双酪氨酸，这意味着可以发现特异性抑制真菌细胞壁组装而不影响哺乳动物细胞的药物。芽殖酵母孢子壁是研究真菌孢子壁形态发生的理想模型。本基金的实验分为三个相互关联的目标：（1）确定孢子外壁的组成和结构，并阐明合成和整合到孢子壁中的组分的生物合成途径;（2）详细说明我们的研究，这些研究表明，长萜醇是营养细胞中糖基化所需的一种必需脂质，（3）应用我们在孢子壁组装研究中获得的知识，定义了构建白色念珠菌细胞壁中壳聚糖/双酪氨酸模块所必需的保守遗传工具包。

DESCRIPTION (provided by applicant): The de novo formation of the spore wall during the process of sporulation in the budding yeast S. cerevisiae provides a powerful, tractable model for the study of fungal cell wall assembly. This grant is focused on elucidating the structure and mechanism of assembly of the outer two layers of the spore wall. These two layers, comprised of the polysaccharide chitosan and the polyphenol dityrosine, are absent from vegetative cells and enable spores to resist a variety of environmental stresses. Importantly, although chitosan and dityrosine are absent from vegetative cell walls in budding yeast they are present in the walls of many pathogenic fungi such as Candida albicans. Chitosan and dityrosine are not found in mammalian extracellular matrices, meaning that drugs may be found that specifically inhibit fungal cell wall assembly without affecting mammalian cells. The budding yeast spore wall provides an excellent model system to study fungal wall morphogenesis. Experiments in this grant are divided into three interrelated aims: (1) define the composition and structure of the outer spore wall and elucidate the biosynthetic pathways by which the components are synthesized and incorporated into the spore wall; (2) elaborate on our studies which have indicated that dolichol, an essential lipid required for glycosylation in vegetative cells, has a novel role in coordinating outer spore wall formation and (3) apply the knowledge gained from our studies of spore wall assembly to define the conserved genetic toolkit essential for construction of the chitosan/dityrosine module of in cell walls of Candida albicans.