Two-component Signaling in candidiasis and aspergillosis

描述（由申请人提供）：本提案是对Fogarty国际中心研究白色念珠菌和烟曲霉的组氨酸激酶[HK]的资金申请。R Calderone博士[乔治敦大学]和李若愚博士[北京大学第一医院，中国北京]的合作努力将用于了解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，以表征来自白色念珠菌的特定HK，而Li博士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在目标1中，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。沿着这一目标，将跟踪感染动物中细胞因子的产生，以评估特异性宿主对野生型和基因缺失突变体的反应。具体目标2将重点转移到体外条件下，并将研究烟曲霉和相应基因缺失菌株与人中性粒细胞的相互作用。在具体目标3中，将通过RT-PCR筛选来自口腔或阴道念珠菌感染患者以及过敏性或侵袭性曲霉病患者的临床标本的HK基因转录。在目标4中，Calderone实验室将完成最初由Li实验室发现的烟曲霉HK基因的分离，并构建基因缺失菌株用于功能研究。总之，李实验室将在免疫研究方面提供专门知识，而卡尔德龙实验室将在分子生物学方面协助李实验室。由于HK在宿主反应中的作用将被确定，因此在这次合作中将产生协同作用，同时我们也将进一步扩大我们对这些生物HK基因功能的理解。

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