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.

摘要(总体、Sill和Dandekar) 拟议的球虫协作研究中心(CCRC)的首要主题是确定 球孢子虫寄主-病原体界面上的分子和途径。我们的长期目标是分析对话 真菌和宿主免疫系统在模型(巨噬细胞和小鼠)和 慢性和传播性感染的背景(在人类中)。我们在基础真菌学方面的专业知识将有助于我们的 球虫类致病因子的测定。我们丰富的临床样本来源 和我们获得技术创新的机会将有助于我们识别 分子、细胞、代谢物和途径，与允许或限制的患者环境相关 以供传播。我们在数据分析方面的专业知识将促进我们的分子发现与 了解与疾病状态和临床结果相关的宿主反应途径。 此外，我们将评估球虫抗原和宿主生物标记物的诊断潜力，从而 填补球孢子菌病诊断方面的现有空白。同时，我们将使关键基础 微生物生物学和宿主反应的发现，推动了真菌发病机制和医学真菌学领域的发展 往前走。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标 抗真菌的发展以及可能被新的或现有的生物制品作为靶点的宿主途径 有利于宿主的免疫反应。