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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.

项目摘要人类微生物组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由宿主与微生物衍生的小分子的相互作用介导的（即，代谢物）。因此，微生物衍生的代谢物与许多自身免疫性、过敏性和免疫性疾病相关。传染病然而，形成这些关联的分子基础的宿主-微生物组电路还没有得到充分的表征，许多微生物衍生的代谢产物甚至还没有正式的鉴定在这个建议中，我们描述了一种策略，以确定和功能特性的微生物来源，从健康和自身免疫患者中分离的代谢物。我们的合作团队将隔离和表征人类微生物组的新型代谢物，将这些关联与人类免疫映射途径，并确定参与微生物衍生代谢物的特定宿主受体。这项建议会建立微生物代谢产物和人体免疫系统功能之间的因果关系。