Molecular Biology Of Lymphocyte & Neuronal Growth

淋巴细胞的分子生物学

• 批准号: 6635973
• 负责人: DAVID BALTIMORE
• 金额: $ 44.57万
• 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/6635973
• 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.

申请人描述：该提案有六个截然不同的目标 与细胞内信号传导事件如何发生的普遍关注联系在一起 免疫和神经系统控制生物体的生理活动。目的 是询问NF-KB转录因子是否在神经元中发挥作用 来自突触的信号传输。 NF-kB 存在于突触中，已知 控制机制使其很有吸引力，认为它可以参与 诸如长时程增强等活动。目标2是利用遗传方法 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 但遗传方法可以解决相互矛盾的结果。目标3是尝试 确定嗅觉神经元何时以及如何在 1000 个编码基因中进行选择 潜在的气味受体，使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 涉及开发改进的 利用基因修饰研究哺乳动物生理学的方法 老鼠。目标 4 是研究控制同源整合的参数 转染小鼠和人类细胞中的DNA。目标5是完善使用方法 慢病毒载体将基因带入小鼠雄性生殖细胞系，从而 通过精子进行转基因。这涉及制作新的更好的载体 允许基因表达。我们还将尝试扩展小鼠的工作 到其他物种。目标 6 是了解小鼠的免疫系统如何避免 与身体正常组织发生反应以及该系统如何失效 自身免疫。这里我们将重点关注 IL-2 受体的作用和 它发送细胞内信号的分子。