CRYPTOCOCCUS NEOFORMANS--A MODEL FOR PATHOGENIC FUNGI

这是一个医学真菌学单位的项目，重点是 跨学科的研究方法，以增加我们对 通过模式病原体的医学重要真菌的病理生物学， 新生隐球菌。在本提案中，我们将使用相互关联的 识别和验证靶标的分子生物学方法 诊断学、疫苗和治疗学的发展。要实现这些目标 目标，该提案被分为四个不同的但 以新生隐球菌为重点的相互关联的项目 病原真菌模型系统。项目1是基因型和 新生葡萄球菌的表型进化。在这些人口研究中， 可以确定药物靶标的一般重要性和有效性； 可以评估酵母菌株漂移的鉴定，这可能会影响 疫苗开发并帮助分子诊断与 影响预后的因素。项目2将研究信号转导途径 调节新生芽孢杆菌的毒力。在这项提案中，双方都保守地 并将解剖独特的特征以允许这些中央通路 用于利用基因表达作为抗真菌药物的靶点。项目 3抗真菌药物靶标的遗传鉴定。 新形态主义者。使用酿酒酵母作为替代品， 温度生长必需基因及其需要量的探讨 对新生葡萄球菌中的氨基酸和维生素进行检测。项目 4是新生隐孢子虫寄主温度生长的遗传控制。 在许多方面，最简单但最重要的毒力表型 将探索新形藻(在37摄氏度下生长)。在这 项目，直接分析必需基因或必需基因 将确定在37摄氏度下生长所必需的物质。一个 从项目2-4的实验中产生的剧毒突变体可以被使用 无论是用于活疫苗还是用于筛选组合文库的工具 在校园里制造的抗真菌化合物的线索。本节目 强调对单一病原体的关注，具有基本但广谱的 和高度互动的基因组学方法进行科学研究 这可以推论到其他真菌。

This program project for a medical mycology unit is focused on an interdisciplinary research approach to increase our understanding of the pathobiology of medically important fungi through the model pathogen, Cryptococcus neoformans. In this proposal we will use interrelated molecular biological approaches to identify and validate targets for the development of diagnostics, vaccines and therapeutics. To achieve these goals, the proposal has been divided into four distinct but interconnected projects which focus on Cryptococcus neoformans as a model system for pathogenic fungi. Project 1 is the genotype and phenotypic evolution of C. neoformans. In these population studies, the general importance and validity of drug targets can be determined; identification of yeast strain drift can be assessed which may affect vaccine development and help molecular diagnostics to interface with prognostic factors. Project 2 will study signal transduction pathways regulating virulence in C. neoformans. In this proposal, both conserved and unique features will be dissected to allow these central pathways for gene expression to be exploited for antifungal drug targets. Project 3 concerns genetic identification of antifungal drug targets in C. neoformans. With the use of saccharomyces cerevisiae as a surrogate, exploration into essential genes for temperature growth and requirements for amino acids and vitamins in C. neoformans will be performed. Project 4 is the genetic controls for host temperature growth in C. neoformans. In many respects the most simple but important virulence phenotype of C. neoformans (growth at 37 degrees Celsius) will be explored. In this project, a direct analysis of genes necessary of genes necessary or essential for growth at 37 degrees Celsius will be identified. A virulent mutants created from experiments in Projects 2-4 can be used either for live vaccines or tools for screening combinatorial libraries made on-campus for leads to antifungal compounds. This program emphasizes a focus on a single pathogen with a basic but broad-spectrum and highly interactive genomic approach to scientific investigations which can be extrapolated to other fungi.