THE IMMUNE SELF-ASSOCIATED STORAGE ORGANELLE (SASO)

免疫自联存储细胞器 (SASO)

基本信息

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
项目类别：
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

项目摘要

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’.

项目概要这项研究调查了身体在面对外来生物和癌症时如何保持“自我”记忆。这种自我认识被认为是至关重要的，有助于教育免疫系统限制自身免疫和相反，许可对“外来”事物的反应该研究的核心集中在新发现的事物上。细胞器，存在于巨噬细胞和一些树突状细胞中，我们称之为自相关存储 Organelle 或简称 SASO 我们相信 SASO 对于“保持”我们的自我认同至关重要。教育我们免疫系统的其余部分，它似乎来自一种隐秘而微妙的“细胞”形式我们的提案在应用切割技术方面是独一无二的——晶格光片成像、囊泡流、质量- 光谱分析法和电子显微镜——连同传统的细胞免疫分析方法和遗传分析方法筛选，以了解免疫系统的这个新描述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促进健康的方法。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作为“自我”。