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

基本信息

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
项目类别：
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

项目摘要

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（总体而言，SIL和Dandekar）拟议中的球孢合作研究中心（CCRC）的总体主题是确定球虫宿主 - 病原体界面处的分子和途径。我们的长期目标是分析对话框在模型（巨噬细胞和小鼠）的背景下，真菌与宿主免疫系统之间以及在慢性和传播感染的背景（在人类中）。我们具有基本真菌学的专业知识将有助于我们确定对引起疾病至关重要的球球菌因子。我们丰富的临床样品来源从加利福尼亚州地方性地区以及我们获得技术创新的机会将有助于我们确定的能力与允许或限制性的患者环境相关的分子，细胞，代谢物和途径进行传播。我们通过数据分析的专业知识将促进我们的分子发现的整合到对与疾病状态和临床结果相关的宿主反应途径产生了解。此外，我们将评估球虫剂抗原和宿主生物标志物的诊断潜力，从而在诊断球菌病的诊断中缩小现有差距。同时，我们将制作关键基本微生物生物学和宿主反应的发现，推动了真菌发病机理和医学真菌学领域向前。最后，通过整合项目和核心的数据，我们希望确定抗真菌发展以及可能由新颖或现有生物制剂作为目标的宿主途径免疫反应支持宿主。