THE IMMUNE SELF-ASSOCIATED STORAGE ORGANELLE (SASO)

免疫自联存储细胞器 (SASO)

• 批准号: 10639168
• 负责人: MATTHEW F KRUMMEL
• 金额: $ 60.68万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-20 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10639168
• 关键词: Antigen Presentation; Antigen-Presenting Cells; Antigens; Area; Autoimmunity; Biological Models; Biological Process; Biology; CRISPR screen; Cell Death; Cells; Competence; Complement; Cytometry; Cytosol; Data; Dendritic Cells; Diagnostic; Educational process of instructing; Electron Microscopy; Engineering; Flow Cytometry; Generations; Genes; Genetic Screening; Goals; Grant; Health; Homeostasis; Image; Immune; Immune system; Immunoassay; Immunologics; Immunotherapeutic agent; In Vitro; Infection; Ingestion; Injury; Intention; Knock-out; Knowledge; Lead; Licensing; Life; Light; Macrophage; Malignant Neoplasms; Mass Spectrum Analysis; Membrane; Memory; Methods; Microscopy; Molecular; Myelogenous; Myeloid Cells; National Institute of Allergy and Infectious Disease; Organelles; Organism; Phagocytosis; Population; Process; Proteins; Proteomics; Reagent; Research; Research Personnel; Rest; Sampling; Self Perception; Self Tolerance; Specific qualifier value; Speed; Surface; Synapses; Systems Biology; T cell differentiation; T-Lymphocyte; Technology; Testing; Time; Tumor Antigens; Tumor Immunity; Tumor-associated macrophages; Vesicle; Work; analytical method; design; draining lymph node; exhaustion; genetic testing; high dimensionality; human disease; improved; in vivo; innovation; interest; lymph nodes; migration; mutant; next generation; novel; programs; tumor

PROJECT SUMMARY This study investigates how the body maintains a memory of ‘Self’. When facing foreign organisms and cancer, this self-knowledge is thought to be critical, serving to educate the immune system to limit autoimmunity and conversely license reactivity to things that are ‘Foreign’. The core of the study focuses on a newly-discovered organelle, found within macrophages and some dendritic cells which we call the Self-Associated Storage Organelle or SASO for short. We believe that the SASO is critical to ‘hold’ our self-identity and subsequently educate the rest of our immune system and it appears to come from a stealthy and subtle form of ‘cell nibbling’.Our proposal is unique in applying cutting technologies—lattice-light sheet imaging, vesicle flow, Mass- spectrometry and Electron Microscopy—together with conventional cellular immunoassay methods and genetic screens, to understand how this newly described component of the immune system works as well as how we can harness it to improve health. The resultant discoveries will be formative for designing new ways to boost anti-tumor immunity, to minimize autoimmunity and to broadly regulate which components of our bodies are seen as ‘Self’.

项目摘要 这项研究探讨了身体如何保持对“自我”的记忆。当面对外来生物和癌症时， 这种自我认识被认为是至关重要的，用于训练免疫系统以限制自身免疫， 相反，许可证反应的东西是'外国'。这项研究的核心集中在一个新发现的 细胞器，在巨噬细胞和一些树突细胞中发现，我们称之为自相关存储 细胞器或简称SASO。我们相信，SASO对“保持”我们的自我认同至关重要， 教育我们的免疫系统的其余部分，它似乎来自一个秘密和微妙的形式'细胞 我们的建议是独特的应用切割技术-晶格光片成像，囊泡流，质量， 光谱法和电子显微镜-与传统的细胞免疫测定方法和遗传 屏幕，以了解这个新描述的免疫系统的组成部分是如何工作的，以及我们如何 可以利用它来改善健康。由此产生的发现将有助于设计新的方法来提高 抗肿瘤免疫，最大限度地减少自身免疫，并广泛调节我们身体的哪些组成部分被视为 作为“自我”。