TWO-COMPONENT SIGNAL PROTEINS OF ASPERGILLUS FUMIGATUS

烟曲霉的双组分信号蛋白

• 批准号: 6313418
• 负责人: Richard Arthur Calderone
• 金额: $ 4.03万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-07 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6313418
• 关键词: Aspergillus; Candida albicans; aspergillosis; biological signal transduction; disease /disorder model; enzyme activity; fungal genetics; fungal proteins; gene deletion mutation; gene targeting; genetic library; genetic strain; genetically modified animals; histidine; laboratory mouse; molecular pathology; phenotype; polymerase chain reaction; protein kinase; protein signal sequence; tissue /cell culture; virulence

DESCRIPTION: This is a Fogarty-NIH proposal which seeks funding for a study of two-component signal transduction proteins from the human pathogenic fungus, Aspergillus fumigatus. The parent grant is entitled, "The response regulator gene (CaSSK1) of Candida albicans, 1 R0l A147047-01. The study will be performed in the laboratories of Drs. Calderone (PI) and Latge (foreign collaborator). Dr. Latge's lab has made numerous contributions to our understanding of the pathogenesis of aspergillosis through both biochemical and molecular approaches. Dr. Calderone's lab has focused their research on the 2-component histidine kinases and the response regulator signal proteins of Candida albicans. He has shown that these proteins (Chk1p and Csk1p) are required for the formation of hyphae and the regulation of a hyphal cell surface protein. Strains deleted in their encoding genes are also avirulent. The long-term objective of this research is to establish the importance of these proteins in the growth and virulence of A. fumigatus. The hypothesis of this proposal is that regulation of growth and virulence in this organism is achieved through 2-component signaling. In other systems, 2-component signaling is required for the expression of multiple virulence factors. Thus, studies of signal pathways in this organism may reveal more about virulence factors than construction of a strain with a single-gene disruption. The specific aims of the proposal include: 1) genes encoding the homologs of the C. albicans Chk1p and Cssk1p are to be cloned and characterized. 2) Strains of A. fumigatus deleted in each of these genes will be constructed and their phenotypes characterized in vitro. 3) The gene deleted strains will be evaluated in an intranasal model of murine invasive aspergillosis. If determined to be important to this organism, our studies may suggest that 2-component proteins are relevant targets for the development of broad-spectrum antifungals.

描述：这是 Fogarty-NIH 的一项提案，旨在为一项研究寻求资金 来自人类病原真菌的双组分信号转导蛋白， 烟曲霉。家长补助金的标题是“响应监管机构 白色念珠菌的基因（CaSSK1），1 R01 A147047-01。该研究将是 在博士的实验室进行。 Calderone (PI) 和 Latge (国外) 合作者）。 Latge 博士的实验室为我们的研究做出了许多贡献 通过生物化学和方法了解曲霉病的发病机制 分子方法。 Calderone 博士的实验室将他们的研究重点放在 2 组分组氨酸激酶和反应调节信号蛋白 白色念珠菌。他证明这些蛋白质（Chk1p 和 Csk1p） 菌丝形成和菌丝细胞调节所需 表面蛋白。编码基因缺失的菌株也是无毒的。 本研究的长期目标是确定以下方面的重要性： 这些蛋白质与烟曲霉的生长和毒力有关。的假设 该建议是，对该生物体的生长和毒力的调节是 通过2分量信号实现。在其他系统中，2 分量信号 是多种毒力因子表达所必需的。因此，研究 该生物体中的信号通路可能比毒力​​因子更能揭示毒力因子 构建具有单基因破坏的菌株。具体目标 该提案包括：1）编码白色念珠菌Chk1p同源物的基因 和 Cssk1p 将被克隆和表征。 2) 烟曲霉菌株 将构建每个基因中的删除及其表型 体外表征。 3) 基因缺失菌株将在 鼠侵袭性曲霉菌病的鼻内模型。如果确定是 对于这种生物体很重要，我们的研究可能表明 2 组分蛋白质 是开发广谱抗真菌药物的相关目标。