Human Natural Killer Cell Biology

人类自然杀伤细胞生物学

• 批准号: 7220655
• 负责人: Frances M. Brodsky
• 金额: $ 144.62万
• 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/7220655
• 关键词: Human; Natural; Killer; Cell; Biology

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）：该计划采用广泛的方法来了解人类自然杀伤（NK）细胞生物学。该计划各单元所代表的不同科学专业知识将集中于两个目标。首先，这些单位之间的合作将阐明控制人类 NK 细胞受体表达和信号传导的途径，并确定它们在 NK 细胞功能中的作用。 Lanier 将定义 CDS 对人类 NK 细胞的作用，并表征新型 NK 细胞受体信号传导途径，重点是 NK 细胞激活。 Parham 将表征影响受体表达（在蛋白质和启动子水平）的 NK 细胞受体多态性，并测试其功能效果。另一个单元将探索影响 NK 细胞受体功能的膜运输途径，并确定信号传导途径和受体多态性如何影响这些途径。这些单位将共同关注影响激活受体和抑制受体信号之间平衡的分子途径，这种平衡对于 NK 细胞功能至关重要。该项目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 感染过程中的作用。将定义疾病及其治疗过程中 NK 细胞亚群表达和受体使用的模式。 该项目的首席研究员（布罗德斯基）拥有分析淋巴细胞膜运输途径的专业知识。虽然对于 NK 细胞来说是新的，布罗德斯基的项目通过应用细胞生物学来定义免疫学和遗传学所涉及的途径，为其他单位提供了焦点。 Parham 和 Lanier 是 NK 细胞领域的专家，有着成功合作的历史。该项目的人员将定期会面，并将受益于专用于显微镜和单克隆抗体生产的核心，以及研究人类 NK 细胞功能所需的共享转染设备。总体而言，该计划将把人类 NK 细胞的基本机制研究与这些细胞在 HIV 感染中的功能联系起来。