Granulysin: A Novel Cytolytic Molecule

颗粒溶素：一种新型溶细胞分子

• 批准号: 6895116
• 负责人: ALAN MICHAEL KRENSKY
• 金额: $ 31.59万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895116
• 关键词: antibiotics; antineoplastics; apoptosis; cell communication molecule; clinical research; cytolysis; differentiation antigens; drug discovery /isolation; genetically modified animals; human tissue; laboratory mouse; membrane channels; protein structure function; synthetic peptide; tissue /cell culture; wound healing

DESCRIPTION (provided by the applicant): Granulysin is a cytolytic molecule expressed by CTL and NK cells with activity against a variety of microbes and tumors. We first identified granulysin as part of a search for genes expressed by T lymphocytes "late" (3-5 days) after T cell activation. Over the first four years of this grant, we described the biosynthesis of granulysin, generated granulysin specific monoclonal antibodies, and characterized the cytolytic and antimicrobial activities of granulysin. In this renewal application, we propose to further define the mechanism of action and in vivo function of granulysin. Specifically, we will further elucidate the molecular pathways involved in granulysin mediated apoptosis; express human granulysin in murine T cells using both transgenic and retroviral technologies, and evaluate the therapeutic efficacy of synthetic peptides corresponding to sub regions of granulysin in vivo. The effects of granulysin or granulysin peptides will be assessed against both microbial and tumor targets. The ultimate goal of these studies is to use granulysin, peptide components, and/or the information gained from the mechanistic studies to develop new antibiotics and/or tumor chemotherapeutic agents.

描述（由申请人提供）：颗粒素是由CTL和NK细胞表达的细胞溶解分子，其活性针对多种微生物和肿瘤。我们首先将颗粒素鉴定为搜索T细胞激活后T淋巴细胞“后期”（3-5天）表达的基因的一部分。在这笔赠款的前四年中，我们描述了颗粒素的生物合成，产生了颗粒素特异性的单克隆抗体，并表征了颗粒素的细胞溶解和抗菌活性。在此更新应用中，我们建议进一步定义颗粒素的作用机理和体内功能。具体而言，我们将进一步阐明参与颗粒素介导的细胞凋亡的分子途径。使用转基因和逆转录病毒技术在鼠T细胞中表达人颗粒素，并评估与体内颗粒素亚区域相对应的合成肽的治疗功效。将对微生物和肿瘤靶标评估​​颗粒素或颗粒肽肽的作用。这些研究的最终目的是使用颗粒素，肽成分和/或从机械研究中获得的信息来开发新的抗生素和/或肿瘤化学治疗剂。