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Programmed Death of Vertebrate Cells Induced by an Ameba Protein

阿米巴蛋白诱导脊椎动物细胞程序性死亡

基本信息

批准号：
9212702
负责人：
Chandler Fulton
金额：
$ 5万
依托单位：
Brandeis University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
1992
资助国家：
美国
起止时间：
1992-03-15 至 1993-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=9212702&HistoricalAwards=false
关键词：
Programmed Death Vertebrate Cells Induced

项目摘要

Long term work in Dr. T. H. Dunnebacke's laboratory, provocative but generally ignored, has shown that an agent from amoebae of Naegleria gruberi induces generations-delayed death of vertebrate cells in culture, and that these dying cells in turn produce an agent that causes death of other vertebrate cells. This remarkable phenomenon has been confirmed, and it has been shown that the cell death has features characteristic of apoptosis. The first goal is to complete and carefully document these new observations. Dunnebacke has purified the agent from amoebae, and has identified it as a protein, which has been partially sequenced. The plan, in collaboration with Dunnebacke, is to use her information to clone the Naegleria gene that encodes the protein, to sequence and characterize this gene and its product, and to determine whether the isolated protein is responsible for the biological activity of the agent. These studies should make this phenomenon a paradigm for future investigations of: 1, the mechanism by which a protein induces generations-delayed apoptosis; 2, how a protein from an amoeba can lead to the production, by dying vertebrate cells, of a product with similar biological activity, as well as the nature of the vertebrate product; and 3, possible therapeutic applications of the protein.

t·h·邓尼巴克博士的实验室进行了一项长期的研究，这项研究具有挑战性，但通常被忽视。研究表明，一种来自格氏奈格里亚变形虫的物质会诱导培养的脊椎动物细胞延迟几代死亡，而这些垂死的细胞又会产生一种物质，导致其他脊椎动物细胞死亡。这一显著现象已得到证实，表明细胞死亡具有凋亡的特征。第一个目标是完成并仔细记录这些新的观察结果。Dunnebacke从变形虫中纯化了这种物质，并将其鉴定为一种蛋白质，并对其进行了部分测序。他们计划与Dunnebacke合作，利用她的信息克隆编码蛋白质的Naegleria基因，对该基因及其产物进行测序和表征，并确定分离的蛋白质是否对制剂的生物活性负责。这些研究应该使这种现象成为未来研究的范例：1，蛋白质诱导代际延迟细胞凋亡的机制；2、来自变形虫的蛋白质如何通过死亡的脊椎动物细胞导致具有类似生物活性的产品的产生，以及脊椎动物产品的性质；第三，这种蛋白质可能的治疗应用。