CAREER: Systems Immunology Approach to Memory T Cell Immune Engineering

首席研究员将研究免疫学的一个基本问题，即记忆T细胞（一种存在于血液中负责免疫保护的细胞类型）如何被选择。新知识的成功应用有望为免疫治疗提供新的工具。此外，还计划针对非stem专业的大一本科生开设全校范围的免疫工程课程。病原体和癌症的疫苗和免疫治疗工程的目标是实现长期的免疫记忆，这是由记忆T和B细胞维持的。在各种B细胞和T细胞亚型中，持久的CD8+ T细胞记忆因其高特异性、细腻的敏感性和持久的杀伤作用而成为一个有吸引力的靶标。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过程，并且它们的表达水平易于操纵，因此我们的目标是结合最近发展的几种T细胞谱技术，系统地研究microRNA调控网络在工程T细胞记忆中的作用。通过询问T细胞受体结合强度决定microRNA调节网络，我们的目标是确定顶级microRNA调节节点，并操纵和测试它们对工程T细胞记忆的重要性。同时，建议利用研究努力来建立免疫工程的教育计划。通过针对非stem专业大一本科生的新校园课程和相关活动，包括学生提出的“工程T细胞免疫”概念，以及向当地中学生和高中生的演讲，我们的教育活动将扩大我们校园和社区的科学参与，同时加强我们拟议的研究工作。因此，拟议的项目创造了研究活动、教育活动和社区外展的协同整合。

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.