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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：
10261376
负责人：
Aaron M Neiman
金额：
$ 35.89万
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 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10261376
关键词：
Antifungal Agents Appearance Biochemistry Biological Assay Biological Models Candida albicans Cell Wall Cell physiology Cells Chemical Structure Chimera organism Chitin Synthase Chitosan Complex Cryptococcus neoformans Cytology Development Drug Targeting Encapsulated Environment Enzyme Inhibitor Drugs Enzymes Evolution Genes Genetic Genetic Screening Genome Goals Grant HIV Haploidy Immunocompromised Host In Vitro Infection Lipids Mannans Mass Spectrum Analysis Mediating Meiosis Membrane Molecular Morphogenesis Mycoses Organelles Pathway interactions Patients Pharmaceutical Preparations Play Polymers Polysaccharides Population Public Health Reaction Regulation Reproduction spores Resistance Role Rupture Saccharomyces cerevisiae Saccharomycetales Signal Transduction Stress Structure Testing Work Yeast Model System Yeasts beta-Glucans cancer therapy dityrosine drug development drug resistant pathogen effective therapy environmental stressor enzyme activity fungal genetics fungus gene function glucan synthase insight metabolomics novel pathogenic fungus polyphenol resistant strain side effect

项目摘要

7. PROJECT SUMMARY/ABSTRACT Fungal infections are a significant public health problem and one difficulty in treatment of these infections is the small number of available antifungal drugs. Moreover, existing treatments suffer both from significant side effects and the frequent appearance of resistant strains. The cell wall is an essential organelle of the fungal cell. Because the cell wall is essential for viability, drugs that inhibit fungal cell wall assembly are potential antifungal agents. Indeed, one major class of current antifungals targets β-glucan synthase, a key enzyme in cell wall synthesis. In budding yeast, the haploid genomes produced by meiosis are encapsulated by a multi-layered spore wall, which allows spores to resist a variety of environmental stresses. The inner layers of the spore wall are composed of mannan and β-glucan, similar to the vegetative cell wall. The outer layers of the spore wall are comprised of the polysaccharide chitosan, the polyphenol dityrosine and a third, poorly characterized component termed Chi. These outer spore wall components are absent from vegetative cell walls and primarily responsible for the stress resistance of spores. Importantly, although chitosan and dityrosine are absent from vegetative cell walls in budding yeast, they are present in the walls of pathogenic fungi. The budding yeast spore wall therefore provides an excellent model system to study fungal wall morphogenesis. This grant is focused on understanding the activity and regulation of conserved enzymes involved in synthesis and assembly of different spore wall components with the long-term goal of identifying new targets for antifungal drug development

7. 项目总结/文摘