Molecules and Pathways at the Coccidioides Host-Pathogen Interface

球孢子菌宿主-病原体界面的分子和途径

• 批准号: 10364963
• 负责人: Satya Dandekar
• 金额: $ 173.6万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10364963
• 关键词: Acute; Antibodies; Antifungal Agents; Antigens; Automobile Driving; Behavior; Biological Markers; Biological Products; Biology; Blood; California; Cells; Cerebrospinal Fluid; Chronic; Clinical; Coccidioides; Coccidioidomycosis; Collaborations; Communication; Cytometry; Data; Data Analyses; Data Set; Development; Diagnosis; Diagnostic; Disease; Disease Outcome; Drug Screening; Foundations; Fungal Antigens; Future; Genetic Transcription; Goals; Growth; Human; Immune; Immune System Diseases; Immune response; Immune system; Infection; Learning; Lung nodule; Medical; Meningitis; Metabolic; Modeling; Molecular; Molecular Profiling; Molecular Target; Mus; Mycoses; Nature; Outcome; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Research; Role; Sampling; Source; Surveys; T cell response; Technology; Testing; The science of Mycology; Therapeutic; Time; Transcript; Treatment Failure; Virulence; Virulence Factors; cell type; chronic infection; desert fever; eosinophil; experimental study; fungus; immunological diversity; laboratory experiment; macrophage; metabolomics; microbial; mouse model; multidisciplinary; mutant; novel; pathogen; response; single-cell RNA sequencing; small molecule; sound; technological innovation; therapeutic development; transcriptome; transcriptomics

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.

总结（Sil 和 Dandekar 总体） 拟议的球孢子菌合作研究中心 (CCRC) 的首要主题是确定 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）和 慢性和播散性感染（人类）的背景。我们在基础真菌学方面的专业知识将有助于我们 确定对引起疾病至关重要的球孢子菌因子。我们丰富的临床样本来源 来自加利福尼亚州的流行地区，我们获得技术创新将有助于我们识别 与允许或限制的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 了解与疾病状态和临床结果相关的宿主反应途径。 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 缩小球孢子菌病诊断方面的现有差距。同时，我们将把关键基础 微生物生物学和宿主反应方面的发现，推动真菌发病机制和医学真菌学领域的发展 向前。最后，通过整合来自项目和核心的数据，我们希望能够确定新的分子靶点 抗真菌的发展以及宿主途径可以成为新型或现有生物制剂的目标，以推动 有利于宿主的免疫反应。