Human Natural Killer Cell Biology

人类自然杀伤细胞生物学

• 批准号: 7123437
• 负责人: Frances M. Brodsky
• 金额: $ 145万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-16 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123437
• 关键词: cell biology; clinical research; natural killer cells

DESCRIPTION (provided by applicant): This program takes a broad approach to gain understanding of human natural killer (NK) cell biology. The varied scientific expertise represented by the units of the program will concentrate on two goals. Firstly, collaboration between the Units will elucidate pathways controlling human NK cell receptor expression and signaling and establish their role in NK cell function. Lanier will define CDS's role on human NK cells and characterize novel NK cell receptor signaling pathways, with emphasis on NK cell activation. Parham will characterize NK cell receptor polymorphisms that influence receptor expression (both at the protein and promoter level) and test their functional effects. Another unit will explore membrane traffic pathways that influence NK cell receptor function and determine how signaling pathways and receptor polymorphisms affect these pathways. Together the units will focus on molecular pathways that influence the balance between signals coming from activating and inhibitory receptors, a balance that is central to NK cell function. The program's second goal is to establish the clinical importance of molecular mechanisms of NK cell function. Nixon and Michaelsson will study the role of NK cells during HIV infection. Patterns of NK cell subset expression and receptor usage during the course of disease and its treatment will be defined. The program's principal investigator (Brodsky) has expertise in analyzing membrane traffic pathways in lymphoid cells. While new to NK cells, Brodsky's program provides a focus for the other units through the application of cell biology to define pathways implicated by the immunology and genetics. Parham and Lanier are experts in the NK cell field and have a history of successful collaboration. The program's personnel will meet regularly and will benefit from cores dedicated to microscopy and to monoclonal antibody production, as well as shared transfection equipment necessary for studying human NK cell function. Overall, this program will link basic mechanistic studies on human NK cells to the functions of these cells in HIV infection.

描述（由申请人提供）：该计划采取广泛的方法来了解人类自然杀手（NK）细胞生物学。该计划单位代表的各种科学专业知识将集中在两个目标上。首先，单元之间的协作将阐明控制人NK细胞受体表达和信号传导并确定其在NK细胞功能中的作用。 Lanier将定义CD在人NK细胞上的作用，并表征新的NK细胞受体信号通路，重点是NK细胞激活。 Parham将表征NK细胞受体多态性影响受体表达（无论是在蛋白质和启动子水平上）并测试其功能效应。另一个单元将探索影响NK细胞受体功能的膜交通路径，并确定信号通路和受体多态性如何影响这些途径。这些单元将集中在影响来自激活和抑制受体的信号之间的平衡的分子途径上，这是NK细胞功能核心的平衡。该计划的第二个目标是确定NK细胞功能分子机制的临床重要性。尼克松和迈克尔森将研究NK细胞在HIV感染中的作用。将定义NK细胞子集表达和受体用法的模式及其治疗方法。 该计划的主要研究者（Brodsky）在分析淋巴样细胞中的膜交通途径方面具有专业知识。 Brodsky的程序是NK细胞的新功能，但通过应用细胞生物学来定义由免疫学和遗传学涉及的途径，为其他单位提供了重点。 Parham和Lanier是NK细胞领域的专家，并拥有成功合作的历史。该计划的人员将定期开会，并将受益于专门用于显微镜和单克隆抗体产生的核心，以及研究人类NK细胞功能所需的共享转染设备。总体而言，该程序将将对人NK细胞的基本机理研究与这些细胞在HIV感染中的功能联系起来。