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Identification and Characterization of Microbial Metabolites in Immunity

免疫中微生物代谢物的鉴定和表征

基本信息

批准号：
10513037
负责人：
Daniel Bartholomew Graham
金额：
$ 78.31万
依托单位：
BROAD INSTITUTE, INC.
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：
2022-05-26 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10513037
关键词：
Agonist Allergic Disease Anatomy Antigen Receptors Antigens Autoimmune Autoimmune Diseases Autoimmunity Cells Chemicals Communicable Diseases Consensus Cues Dendritic Cells Digestion Disease Ecosystem Epigenetic Process Epithelial Evolution Exposure to Fractionation G-Protein-Coupled Receptors GPR35 gene Gene Cluster Genetic Glycolipids Health Human Human Microbiome Hypersensitivity Immune Immune response Immunity Immunologic Receptors Inflammatory Innate Immune Response Libraries Ligands Lymphocyte Machine Learning Maps Mediating Metabolic Metagenomics Microbe Molecular Nature Nutrient Pathology Pathway interactions Patients Physiological Reporter Role Shapes Signal Transduction T cell differentiation Training Xenobiotics base cell behavior commensal microbes conditioning cytokine desensitization host microbiome immune function immune system function immunoregulation innate immune pathways innovation microbial microbiome novel peripheral tolerance receptor response small molecule therapeutic development uptake

项目摘要

PROJECT SUMMARY The human microbiome is a key regulator of host immune function, and growing consensus suggests this relationship is likely mediated by host interactions with microbial derived small molecules (i.e., metabolites). Accordingly, microbial derived metabolites have been associated with numerous autoimmune, allergic, and infectious diseases. However, the host-microbiome circuits that form the molecular basis of these associations have not been fully characterized, and many microbial derived metabolites have not even been formally identified. In this proposal, we describe a strategy to identify and functionally characterize microbial derived metabolites isolated from patients in health and autoimmunity. Our collaborative team will isolate and characterize novel metabolites from the human microbiome, map these associations to human immune pathways, and identify the specific host receptors that engage microbial derived metabolites. This proposal will establish causal relationships between microbial metabolites and human immune system function.

项目总结人类微生物群是宿主免疫功能的关键调节器，越来越多的共识表明这一点这种关系可能是通过宿主与微生物衍生的小分子(即代谢物)的相互作用来调节的。因此，微生物衍生的代谢物与许多自身免疫、过敏和传染病。然而，构成这些联系的分子基础的宿主-微生物组回路尚未得到充分的表征，许多微生物衍生的代谢物甚至还没有正式确认身份。在这项提案中，我们描述了一种鉴定和功能表征微生物来源的策略从健康和自身免疫患者中分离出的代谢物。我们的协作团队将隔离和从人类微生物组中鉴定新的代谢物，将这些关系映射到人类免疫系统途径，并确定与微生物衍生代谢物结合的特定宿主受体。这项提议将建立微生物代谢产物与人体免疫系统功能之间的因果关系。