CAREER: Systems Immunology Approach to Memory T Cell Immune Engineering

首席研究员将研究免疫学中的一个基本问题，即如何选择记忆T细胞，这是一种存在于血液中负责免疫保护的细胞类型。新知识的成功应用有望为免疫治疗提供新的工具。还计划在全校范围内为非STEM专业的一年级本科生开设免疫工程课程。针对病原体和癌症的疫苗和免疫治疗工程的目标是实现长期免疫记忆，这种记忆是由记忆T和B细胞维持的。在各种B和T细胞亚型中，CD8+T细胞记忆功能因其高度的特异性、敏感度和持久的杀伤作用而备受关注。基于高亲和力T细胞受体的T细胞工程在癌症和持续病毒感染方面显示出巨大的治疗潜力。然而，一个关键的问题是如何培养这些T细胞来正确地形成记忆。由于microRNAs参与了许多生物学过程，包括记忆T细胞的产生，并且其表达水平易于操纵，我们的目标是结合最近发展的几种T细胞图谱技术来系统地研究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，我们的目标是识别顶级microRNA调控节点，并操纵和测试它们对设计T细胞记忆的重要性。同时，建议利用研究努力建立免疫工程方面的教育计划。通过一门面向非STEM专业大一本科生的新的校园课程和相关活动，包括学生生成的“工程师T细胞免疫”概念和向当地初中生和高中生介绍情况，我们的教育活动将扩大我们校园和社区对科学的参与，同时加强我们拟议的研究努力。因此，拟议的项目创造了研究活动、教育活动和面向社区的宣传活动的协同整合。

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.