Cellular Decision Making

细胞决策

基本信息

批准号：
10822506
负责人：
Orion D Weiner
金额：
$ 9.34万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2026-05-31
项目状态：
未结题

项目摘要

PROJECT SUMMARY/ABSTRACT My lab seeks to define the molecular logic of complex cell behaviors— how cells go from sets of interacting molecules to the emergent properties of living systems. We currently focus on three questions: how neutrophils control their shape and movement, how lymphocytes detect rare foreign peptides in a sea of self- peptides, and how mouse embryonic stem cells regulate transcriptional activation. Studying a diversity of cell types and behaviors makes it easier to identify the general principles of cellular decision-making beyond the particulars of a given system. And it opens up more interfaces for cross pollination between different projects in the lab. Transformative science often happens at interfaces, so we seek to borrow tools and concepts from other fields to address open questions in cell biology and frequently develop new tools when they are needed to accelerate progress. For instance, optogenetics enables us to plug into defined signaling nodes and test the logic of subcircuits in a manner that circumvents the feedback, redundancy, and compensation that confound investigation with standard approaches. Our most common strategy is to pair biosensors for visualizing the quantitative dynamics of these processes in living cells with precision tools to control the regulators of these behaviors. For cell migration, we are breaking down the complex process of directed movement into its fundamental pieces—how a cell decides to initiate a protrusion, how the shape of the protrusion is specified, how the protrusions compete with one another to enable cell polarity, and how this process is biased by external gradients. For T cell activation, we are investigating how cells convert small differences in antigen binding to large changes in cell activation by leveraging a light-responsive T cell antigen. Finally, we are investigating the logic of transcriptional activation—in particular how enhancers activate promoters and how transcription factor dynamics specifies the pattern of gene activation.

项目摘要/摘要我的实验室试图定义复杂细胞行为的分子逻辑 - 细胞如何从相互作用集中分子到生命系统的新兴特性。我们目前专注于三个问题：中性粒细胞控制其形状和运动，淋巴细胞如何在自我的海洋中检测到稀有的外辣椒肽以及小鼠胚胎干细胞如何调节转录激活。研究各种细胞类型和行为使确定蜂窝决策的一般原则变得更加容易给定系统的细节。它为不同项目之间的交叉授粉打开了更多的接口在实验室。变革性科学经常发生在界面上，因此我们寻求从中借用工具和概念其他领域可以解决细胞生物学中的开放问题，并在需要时经常开发新工具加速进步。例如，光遗传学使我们能够插入定义的信号节点并测试子电路的逻辑，以绕过混淆的反馈，冗余和补偿的方式使用标准方法进行调查。我们最常见的策略是将生物传感器配对以可视化这些过程的定量动力学在活细胞中使用精确的工具来控制这些调节器行为。对于细胞迁移，我们将定向运动的复杂过程分解为基本碎片 - 细胞如何决定启动蛋白质，如何指定蛋白质的形状，突起如何相互竞争以使细胞极性启用细胞极性，以及该过程如何偏见外部梯度。对于T细胞激活，我们正在研究细胞如何转化抗原的微小差异通过利用光响应性T细胞抗原来与细胞活化的巨大变化结合。最后，我们是研究转录激活的逻辑 - 特别是增强子如何激活启动子以及如何转录因子动力学指定基因激活的模式。