Two-component Signaling in candidiasis and aspergillosis

描述(由申请人提供)：这项建议是向福格蒂国际中心申请资金，以研究白色念珠菌和烟曲霉的组氨酸激酶[HK]。将利用R Calderone博士[乔治敦大学]和李若瑜博士[北京大学第一医院，北京，中国]的合作努力，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，以确定来自白色念珠菌的特定HK的特征，而Li博士则研究宿主免疫和曲霉病的发病机制，因此，该建议结合了不同重点实验室的努力该项目有四个具体目标：目标1，将在每种疾病的动物模型中研究两种生物的HK基因的时间表达。根据这一目标，将在感染动物中产生细胞因子，以评估特定宿主对野生型和基因缺失突变体的贡献2将重点转移到体外条件下，并将研究烟曲霉菌和相应的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，对口腔或阴道念珠菌病患者以及过敏性或侵袭性曲霉病患者的临床标本进行RT-PCR检测HK基因转录。在目标4中，Calderone实验室将完成Li实验室最初发现的A fumigatus HK基因的分离，并构建用于功能研究的基因缺失菌株。总而言之，LI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LI实验室进行分子生物学研究。在这次合作中，由于HK在宿主反应中的作用将被明确，同时我们也将如预期的那样进一步扩大我们对这些生物的HK基因功能的理解，这一合作也将为NIH父母对卡尔德隆博士的资助提供新的方向

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