CAREER: Systems Immunology Approach to Memory T Cell Immune Engineering

职业：记忆 T 细胞免疫工程的系统免疫学方法

• 批准号: 2149547
• 负责人: Jenny Jiang
• 金额: $ 54.96万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2149547&HistoricalAwards=false
• 关键词: CAREER; Systems; Immunology; Approach; Memory

PI: Jiang , NingProposal No: 1653866The principal investigator will examine a fundamental question in immunology, namely how memory T cells, a cell type present in blood responsible for immune protection, are selected. Successful application of new knowledge gained is expected to provide new tools for immunotherapy. It is also planned to develop campus-wide course on immune engineering aimed at freshman undergraduates for non-STEM majors.The goal of engineering of vaccine and immune therapy for pathogens and cancers is to achieve long-term immune memory, which is maintained by memory T and B cells. Among various B and T cell subtypes, the long lasting CD8+ T cell memory is an attractive target because of its high specificity, exquisite sensitivity, and durable killing effect. High affinity T cell receptor-based T cell engineering has shown great therapeutic potential in cancer and persistent viral infection. However, a critical problem is how to educate these T cells to properly form memory. Since microRNAs have been implicated in many biological processes including memory T cell generation and their expression levels are easy to manipulate, we aim to combine several recently developed technologies in T cell profiling to systematically study the role of microRNA regulatory network in engineering T cell memory in this proposal. By interrogating T cell receptor binding strength dictated microRNA regulatory networks, our goal is to identify top microRNA regulatory nodes and manipulate and test their importance to engineering T cell memory. At the same time, it is proposed to leverage research effort to build an educational program in immune engineering. Through a new campus-wide course aimed at freshman undergraduates in non-STEM majors and associated activities including student-generated concepts for "engineer T cell immunity" and presentations to local middle and high school students, our educational activities will broaden participation in science on our campus and in our community, while simultaneously enhancing our proposed research efforts. Thus, the proposed project creates a synergistic integration of research activities, educational activities, and outreach to the community.

主要研究者：Jiang，Ning提案编号：1653866主要研究者将研究免疫学中的一个基本问题，即如何选择记忆T细胞，一种存在于血液中负责免疫保护的细胞类型。 所获得的新知识的成功应用有望为免疫治疗提供新的工具。针对非STEM专业的大一新生，计划开设免疫工程学的全校区课程。针对病原体和癌症的疫苗和免疫治疗工程学的目标是实现长期免疫记忆，这种记忆由记忆T和B细胞维持。在各种B和T细胞亚型中，持久的CD8+ T细胞记忆是一个有吸引力的靶点，因为它具有高特异性、灵敏度和持久的杀伤作用。基于高亲和力T细胞受体的T细胞工程在癌症和持续性病毒感染中显示出巨大的治疗潜力。然而，一个关键的问题是如何教育这些T细胞正确地形成记忆。由于microRNA参与了包括记忆T细胞生成在内的许多生物学过程，并且其表达水平易于操纵，因此我们的目标是将最近开发的几种T细胞分析技术联合收割机结合起来，系统地研究microRNA调控网络在T细胞记忆工程中的作用。通过询问T细胞受体结合强度决定的microRNA调控网络，我们的目标是确定顶级microRNA调控节点，并操纵和测试它们对工程化T细胞记忆的重要性。同时，建议利用研究工作建立免疫工程教育计划。通过一个新的校园范围内的课程，针对非STEM专业的大一本科生和相关活动，包括学生产生的“工程师T细胞免疫”的概念和演示给当地初中和高中学生，我们的教育活动将扩大在我们的校园和我们的社区科学的参与，同时提高我们提出的研究工作。因此，拟议的项目创造了一个协同整合的研究活动，教育活动，并推广到社区。