Molecules and Pathways at the Coccidioides Host-Pathogen Interface

总结（总体，Sil和Dandekar） 拟议的球孢子菌合作研究中心（CCRC）的首要主题是确定 在球孢子菌宿主-病原体界面的分子和途径。我们的长期目标是分析对话 在模型（巨噬细胞和小鼠）的背景下， 慢性和播散性感染（人类）的背景下。我们在基础真菌学方面的专业知识将有助于我们 确定引起疾病的关键球孢子菌因子。我们丰富的临床样本来源 从加州的流行地区，我们获得技术创新将促进我们的能力， 与患者环境相关的分子、细胞、代谢物和途径， 用于传播。我们在数据分析方面的专业知识将促进我们的分子发现的整合， 产生与疾病状态和临床结果相关的宿主反应途径的理解。 此外，我们将评估球孢子菌抗原和宿主生物标志物的诊断潜力，从而 填补了球孢子菌病诊断方面的现有空白。与此同时，我们将使关键的基本 微生物生物学和宿主反应方面的发现，推动了真菌发病机理和医学真菌学领域的发展 性新最后，通过整合来自项目和核心的数据，我们希望确定新的分子靶点， 抗真菌的发展以及宿主途径，可以靶向新的或现有的生物制剂，以提示 有利于宿主的免疫反应

Summary (Overall, Sil and Dandekar) The overarching theme of the proposed Coccidioides Collaborative Research Center (CCRC) is to identify molecules and pathways at the Coccidioides host-pathogen interface. Our long-term goal is to analyze the dialog between fungus and the host immune system in the context of models (macrophages and mice) and in the context of chronic and disseminated infections (in humans). Our expertise with basic mycology will facilitate our determination of Coccidioides factors that are critical for causing disease. Our rich source of clinical samples from the endemic region of California and our access to technological innovation will facilitate our ability to identify molecules, cells, metabolites, and pathways that correlate with a patient context that is permissive or restrictive for dissemination. Our expertise with data analysis will promote the integration of our molecular findings to generate an understanding of host response pathways that are correlated with disease state and clinical outcome. Additionally, we will evaluate the diagnostic potential of Coccidioides antigens and host biomarkers, thereby closing existing gaps in the diagnosis of coccidioidomycosis. At the same time, we will make key basic discoveries in microbial biology and host response, driving the field of fungal pathogenesis and medical mycology forward. Finally, by integrating the data from Projects and Cores, we hope to identify new molecular targets for anti-fungal development as well as host pathways that could be targeted by novel or existing biologics to tip the immune response in favor of the host.