Assembly and Function of the Yeast Spore Wall

酵母孢子壁的组装和功能

基本信息

批准号：
8758020
负责人：
Aaron M Neiman
金额：
$ 33.02万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-12 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8758020
关键词：
Affect Antifungal Agents Behavior Control Biochemistry Biological Models Candida albicans Cell Wall Cells Chemical Structure Chemicals Chitin Synthase Chitosan Complex Cytoplasm Cytosol Data Development Dolichol Drug Targeting Encapsulated Endosomes Environment Enzymes Extracellular Matrix Family Genes Genetic Genome Grant Haploidy Homologous Gene Knock-out Knowledge Laboratories Link Lipids Mammalian Cell Mass Spectrum Analysis Mediating Meiosis Membrane Metabolic Pathway Methods Morphogenesis Morphology Names Nuclear Magnetic Resonance Organelles Pathway interactions Pharmaceutical Preparations Play Polymers Polysaccharides Population Process Property Proteins Regulation Reproduction spores Role Saccharomyces cerevisiae Saccharomycetales Signaling Molecule Stress Structure Study models Surface System Techniques Testing Time Tyrosine Video Microscopy Yeasts cell type dityrosine fungal genetics fungus glycosylation improved mutant novel polyphenol public health relevance research study solid state nuclear magnetic resonance two-dimensional

项目摘要

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.

描述（由申请人提供）：在发芽的酵母菌S.酿酒酵母中孢子的过程中孢子壁的从头形成提供了一种强大的，可拖延的模型，用于研究真菌细胞壁组件的研究。该赠款的重点是阐明孢子壁外部两层组装的结构和机理。这两个层由多糖壳聚糖和多酚二乙糖组成，是营养细胞中不存在的，使孢子能够抵抗各种环境应力。重要的是，尽管在萌芽的酵母中没有壳聚糖和dityrosine，但它们存在于许多致病真菌（例如白色念珠菌）的壁中。在哺乳动物的细胞外基质中未发现壳聚糖和二乙氨酸，这意味着可以发现药物专门抑制真菌细胞壁组装而不会影响哺乳动物细胞。萌芽的酵母菌壁为研究真菌壁形态发生提供了出色的模型系统。该赠款中的实验分为三个相互关联的目的：（1）定义孢子壁的组成和结构，并阐明将成分合成并掺入孢子壁的生物合成途径； (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.