Two-component Signaling in candidiasis and aspergillosis

念珠菌病和曲霉病的双组分信号传导

• 批准号: 6692618
• 负责人: Richard Arthur Calderone
• 金额: $ 3.37万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-17 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6692618
• 关键词: Candida albicans; aspergillosis; biological signal transduction; candidiasis; clinical research; cytokine; enzyme linked immunosorbent assay; fungal genetics; gene deletion mutation; gene expression; genetic transcription; histidine; human subject; laboratory mouse; polymerase chain reaction; respiratory infections

DESCRIPTION (provided by applicant): This proposal is a request for funds from the Fogarty International Center to study the histidine kinases [HK] of Candida albicans and Aspergillus fumigatus The collaborative efforts of Dr R Calderone [Georgetown University] and Dr Ruoyu Li [Peking University First Hospital, Beijing, China] are to be utilized to understand the role of HK genes in the pathogenesis of candidiasis and aspergillosis. Dr Calderone is currently funded by the NIH-NIAID to characterize a specific HK from C albicans, while Dr. Li studies host immunity and the pathogenesis of aspergillosis Thus, the proposal combines the efforts of differently focused laboratories The project has four specific aims In aim 1, the temporal expression of HK genes from both organisms will be studied in animal models of each disease. Along with this objective, cytokine production in infected animals will be followed to assess the contribution of specific host responses to wild type and gene-deleted mutants Specific aim 2 will shift in emphasis to in vitro conditions, and the interaction ofA fumigatus and the corresponding gene-deleted strains with human neutrophils will be studied. In specific aim 3, clinical specimens from patients with oral or vaginal candidiasis infections as well as those with allergic or invasive aspergillosis will be screened by RT-PCR for HK gene transcription. In aim 4, the Calderone laboratory will complete the isolation of an A fumigatus HK gene originally found by the Li laboratory and construct gene-deleted strains for functional studies. In summary, the Li laboratory will provide expertise in the studies of immunity while the Calderone laboratory will assist the Li laboratory in molecular biology. Synergy will occur during this collaboration since the role of the HK in host responses will be defined while we will also further expand our understanding of the functions of HK genes from these organisms As expected, this collaboration will also provide new directions for the NIH parent grant of Dr Calderone

描述（由申请人提供）：本提案是向福格蒂国际中心申请资金研究白色念珠菌和烟曲霉的组氨酸激酶 [HK] R Calderone 博士 [乔治敦大学] 和李若宇博士 [北京] 的合作努力中国北京大学第一医院]将用于了解 HK 基因在念珠菌病和曲霉病发病机制中的作用。 Calderone 博士目前由 NIH-NIAID 资助，以描述白色念珠菌的特定 HK，而 Li 博士则研究宿主免疫和曲霉病的发病机制。因此，该提案结合了不同重点实验室的努力。该项目有四个具体目标如图 1 所示，将在每种疾病的动物模型中研究两种生物体 HK 基因的时间表达。除此目标外，还将跟踪受感染动物中细胞因子的产生，以评估特定宿主对野生型和基因删除突变体的反应的贡献具体目标 2 将重点转向体外条件以及烟曲霉和相应基因的相互作用-将研究具有人类中性粒细胞的删除菌株。在具体目标3中，将通过RT-PCR对口腔或阴道念珠菌病感染以及过敏性或侵袭性曲霉病患者的临床标本进行HK基因转录筛查。在目标4中，Calderone实验室将完成Li实验室最初发现的烟曲霉HK基因的分离，并构建基因缺失菌株用于功能研究。综上所述，李实验室将提供免疫研究方面的专业知识，而Calderone实验室将协助李实验室进行分子生物学研究。此次合作期间将产生协同作用，因为 HK 在宿主反应中的作用将被定义，同时我们还将进一步扩大我们对这些生物体 HK 基因功能的理解正如预期的那样，这次合作也将为 NIH 家长资助提供新的方向卡尔德龙博士的