Granulysin: A Novel Cytolytic Molecule

颗粒溶素：一种新型溶细胞分子

• 批准号: 6370107
• 负责人: ALAN MICHAEL KRENSKY
• 金额: $ 31.2万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6370107
• 关键词: B cell lymphoma; Mycobacterium tuberculosis; antibiotics; antineoplastics; cell communication molecule; cytolysis; genetically modified animals; human T cell leukemia; human tissue; laboratory mouse; microarray technology; protein structure function; recombinant proteins; synthetic peptide; tissue /cell culture

DESCRIPTION(provided by applicant): Granulysin is a novel cytolytic molecule expressed by CTh 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 three years of this grant we described the biosynthesis of granulysin, made granulysin specific monoclonal antibodies, and showed cytolytic and antimicrobial activity of granulysin. Perhaps most exciting is the considerable cytolytic activity against Mycobacterium tuberculosis. In this renewal application, we propose to further define the mechanism of action and in vivo function of granulysin. Specifically, we will use microarray technology to identify pathways of action, examine these pathways biochemically using a variety of techniques, express granulysin in transgenic mouse models, and evaluate therapeutic efficacy of recombinant human granulysin and synthetic granulysin derived peptides in vivo. These studies will examine granulysin activity 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 proposed mechanistic studies to develop new antibiotics and/or tumor chemotherapeutic agents.

描述（由申请人提供）：颗粒素是一种新型的细胞溶解分子，该分子由CTH和NK细胞表达，其活性针对多种微生物，并且 肿瘤。我们首先将颗粒素鉴定为搜索表达基因的一部分 T细胞激活后T淋巴细胞“晚期”（3-5天）。在第一个 这笔赠款的三年我们描述了颗粒素的生物合成， 颗粒素特异性的单克隆抗体，并显示出细胞溶解和 颗粒素的抗菌活性。也许最令人兴奋的是很大的 对结核分枝杆菌的细胞溶解活性。在此续约中 应用，我们建议进一步定义作用机理和体内的机理 颗粒素的功能。具体来说，我们将使用微阵列技术来 识别作用途径，使用A进行生化检查这些途径 多种技术，在转基因小鼠模型中表达颗粒素，以及 评估重组人颗粒素和合成的治疗功效 颗粒素在体内衍生的肽。这些研究将检查颗粒素 针对微生物和肿瘤靶标的活性。这些的最终目标 研究是使用颗粒素，肽成分和/或获得的信息。 从拟议的机械研究中，开发新的抗生素和/或肿瘤 化学治疗剂。