Quantitative Studies of the Immunological Synapse

免疫突触的定量研究

• 批准号: 6422943
• 负责人: JAY T. GROVES
• 金额: $ 44万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6422943
• 关键词: T cell receptor; T lymphocyte; antigen presentation; cell adhesion molecules; cell cell interaction; cellular immunity; computer simulation; immune system; intermolecular interaction; mathematical model; membrane transport proteins; microarray technology; model design /development; molecular shape; natural killer cells; protein transport; synaptogenesis

DESCRIPTION (provided by applicant): Cells interact with each other and their environment through myriad membrane associated receptors and signaling molecules. In addition to individual receptor-ligand binding, spatial rearrangement of receptors into complex patterns (synapses) is rapidly emerging as a broadly significant aspect of cell recognition. Two prominent examples, which will be the foci of this investigation, are the T-cell and NK-cell immunological synapses. The PI's are mounting a quantitative investigation of the physical characteristics and principles governing the reorganization events that lead to synapse formation. They have developed a theoretical model, which compares well with experimental observations, and suggests that the essential features of immunological synapse formation are the result of spontaneous self-organization processes. Here, they propose to test and develop this hypothesis. A three-pronged investigative platform, that combines sophisticated theoretical calculations and computer simulations with novel membrane experiments in reconstituted lipid membranes and living cells, has been formulated to meet the specific aims. In aim 1, they develop sophisticated theoretical and computational tools, and use these methods and experiments to understand the differential morphology of T cell and NK cell synapses. In aim 2, they perform a stability analysis of their model and this, in conjunction with experiments, will allow them to study how key cell surface parameters regulate synapse formation. In aim 3, they determine the effects of regulatory factors within the cell on synapse formation. In aim 4, will use a genetic algorithm to explore other synaptic patterns and will perform experiments to determine if such patterns can be observed based on the current vocabulary of known molecular interactions and cell types, or based on synthetic interactions. These studies will provide a deep and quantitative understanding of synaptic pattern formation in the immune system and may lead to novel biomimetic and therapeutic approaches.

描述（由申请人提供）：细胞彼此相互作用及其相互作用 通过无数膜相关的受体和信号传导的环境 分子。除了单个受体配体结合，空间 受体重新排列为复杂的模式（突触）正在迅速出现 作为细胞识别的广泛重要方面。两个突出的例子， 这将是本研究的重点，是T细胞和NK细胞 免疫突触。 PI正在进行对 负责重组事件的身体特征和原则 这导致突触形成。他们开发了一个理论模型，该模型 与实验观察结果很好，并表明必需 免疫突触形成的特征是自发的结果 自组织过程。在这里，他们建议测试和开发这个 假设。一个三管齐下的调查平台，结合了复杂的 具有新膜的理论计算和计算机模拟 在重构的脂质膜和活细胞中进行的实验已经是 制定符合特定目标。在AIM 1中，他们发展成熟 理论和计算工具，并使用这些方法和实验来 了解T细胞和NK细胞突触的差异形态。目标 2，他们对其模型进行稳定分析，并结合使用 通过实验，他们将允许他们研究关键细胞表面参数 调节突触形成。在AIM 3中，他们确定了监管的影响 牢房内突触形成的因素。在AIM 4中，将使用遗传 探索其他突触模式的算法，并将执行实验 根据当前的词汇来确定是否可以观察到这种模式 已知的分子相互作用和细胞类型，或基于合成 互动。这些研究将提供深刻而定量的理解 免疫系统中突触模式形成，可能导致新颖 仿生和治疗方法。