CRYPTOCOCCUS NEOFORMANS--A MODEL FOR PATHOGENIC FUNGI

新型隐球菌——病原真菌的模型

• 批准号: 6591620
• 负责人: John R. Perfect
• 金额: $ 4.01万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6591620
• 关键词: Cryptococcus neoformans; fungal genetics; virulence

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.

这个医学真菌学单位的计划项目的重点是一个 跨学科的研究方法，以增加我们对 医学上重要的真菌通过模式病原体的病理生物学， 新型隐球菌。在本建议中，我们将使用相互关联的 分子生物学方法来识别和验证目标， 诊断、疫苗和治疗的发展。实现这些 目标，该提案分为四个不同的，但 相互关联的项目，重点是新型隐球菌作为一种 病原真菌的模型系统。项目1是基因型， C.表型进化新人类在这些人口研究中， 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， 疫苗开发和帮助分子诊断接口， 预后因素项目2将研究信号转导途径 调节C.新人类在这一建议中，两个保守的 和独特的特征将被解剖， 用于抗真菌药物靶点的基因表达。项目 3涉及C. 新人类使用酿酒酵母作为替代物， 温度生长必需基因的探索及需求 C中的氨基酸和维生素将执行新形式。项目 4是控制寄主温度增长的遗传因子。新人类 在许多方面，最简单但最重要的毒力表型 C.新形式（生长在37摄氏度）将被探索。在这 项目，直接分析必要的基因或 将确定在37摄氏度下生长所必需的。一 可以使用从项目2 - 4中的实验中产生的毒性突变体 用于活疫苗或用于筛选组合文库的工具 在校园里制造的抗真菌化合物这个程序 强调关注单一病原体， 和高度互动的基因组方法进行科学研究 这可以推广到其他真菌。