Molecular Biology Of Lymphocyte & Neuronal Growth

淋巴细胞的分子生物学

• 批准号: 6722825
• 负责人: DAVID BALTIMORE
• 金额: $ 38.31万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6722825
• 关键词: apoptosis; autoimmunity; biotechnology; chemoreceptors; cytokine receptors; developmental genetics; developmental neurobiology; gene rearrangement; genetically modified animals; immunogenetics; immunoglobulin genes; interleukin 2; laboratory mouse; leukocyte activation /transformation; long term potentiation; neurogenetics; neuroimmunomodulation; nuclear factor kappa beta; olfactions; tissue /cell culture; transfection; transfection /expression vector

APPLICANT'S DESCRIPTION: There are six fairly disparate aims in this proposal linked by a general concern with how intracellular signaling events in the immune and nervous systems control physiological activities of organisms. Aim is to ask whether the NF-KB transcription factor plays a role in neuronal transmission of signals from synapses. NF-kB is found at synapses and its known control mechanisms make it attractive to think that it could be involved in such activities as long term potentiation. Aim 2 is to use genetic methods to understand activation of NF-kB and of the JNK signaling pathway by tumor necrosis factor and Fas ligand. These pathways have been extensively studied but with conflicting results that genetic methods can resolve. Aim 3 is to try to determine when and how olfactory neurons chose among the 1000 genes encoding potential odor receptors so that one cell expresses only one receptor. This is a problem of gene control in the nervous system that might be analogous to what occurs in the immune system. Aims 4 and 5 relate to the development of improved methods of investigation of mammalian physiology using genetic modifications in mice. Aim 4 is to study the parameters that control homologous integration of transfected DNA in mouse and human cells. Aim 5 is to perfect a method of using lentivirus vectors to bring genes into the mouse male germ cell line, thus doing trangenesis through the sperm. This involves making new better vectors that allow for gene expression. We will also try to extend the work from mice to other species. Aim 6 is to understand how a mouse's immune system avoids reacting with normal tissues of the body and how this system fails in autoimmunity. We will focus here on the role of the IL-2 receptor and the molecules by which it sends intracellular signals.

申请人的描述：在这个建议中有六个相当不同的目标 这与人们普遍关注的细胞内信号传导事件如何联系在一起， 免疫系统和神经系统控制生物体的生理活动。目的 目的是研究NF-κ B转录因子是否在神经元凋亡中发挥作用。 突触传递信号的过程。NF-kB存在于突触中， 控制机制使它有吸引力地认为它可以参与 如长期增效等。目标二是利用遗传学方法， 了解肿瘤对NF-kB和JNK信号通路的激活 坏死因子和Fas配体。这些途径已被广泛研究 但遗传学方法可以解决相互矛盾的结果。目标3：尝试 为了确定嗅觉神经元何时以及如何在1000个编码 潜在的气味受体，因此一个细胞只表达一种受体。这是 神经系统中的基因控制问题可能类似于 发生在免疫系统中。目标4和5涉及改进的 使用遗传修饰研究哺乳动物生理学的方法， 小鼠目的4是研究控制同源整合的参数， 在小鼠和人类细胞中转染DNA。目的五是完善一种使用方法 慢病毒载体将基因导入小鼠雄性生殖细胞系， 通过精子进行转基因这涉及到制造新的更好的载体 让基因得以表达。我们还将尝试将这项工作从老鼠身上扩展开来， 其他物种。目的6是了解小鼠的免疫系统如何避免 与身体的正常组织发生反应，以及这个系统如何在 自身免疫我们将在这里集中讨论IL-2受体的作用， 传递细胞内信号的分子。