Molecular Biology Of Lymphocyte & Neuronal Growth

申请人描述：这份提案有六个截然不同的目标 与一个普遍的担忧有关，即细胞内信号事件如何在 免疫和神经系统控制着生物体的生理活动。目标 是要问核因子-KB转录因子是否在神经细胞中起作用 从突触传递信号。核因子-kB在突触中被发现，其已知 控制机制使它有吸引力地认为它可能参与 诸如长时程增强之类的活动。目标2是使用遗传方法来 了解肿瘤对核因子-kB和JNK信号通路的激活作用 肿瘤坏死因子和Fas配体。这些途径已经得到了广泛的研究 但遗传方法可以解决的结果相互矛盾。目标3是尝试 为了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个受体。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和目标5涉及改进的发展 利用遗传修饰研究哺乳动物生理学的方法 老鼠。目的4是研究控制同源整合的参数。 在小鼠和人细胞中转导DNA。目标5是完善一种使用 慢病毒载体将基因导入小鼠雄性生殖细胞系，从而 通过精子进行转基因。这涉及到制造新的更好的载体 可以进行基因表达。我们还将努力将这项工作从MICE扩展到 传给其他物种。目标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 自身免疫力。我们将在这里集中讨论IL-2受体和 它传递细胞内信号的分子。

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.