Cellular Decision Making

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--细胞如何从一系列相互作用 分子与生命系统的新特性的关系。我们目前关注三个问题：如何 中性粒细胞控制着它们的形状和运动，淋巴细胞如何在一片自我的海洋中检测到稀有的外来肽 多肽，以及小鼠胚胎干细胞如何调节转录激活。研究细胞的多样性 类型和行为可以更容易地识别细胞决策的一般原则，而不是 给定系统的详细信息。它为不同项目之间的异花授粉开辟了更多的接口 在实验室里。变革性的科学经常发生在界面上，所以我们寻求借用工具和概念 其他领域，以解决细胞生物学中的公开问题，并在需要时经常开发新工具 加快推进。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，避免反馈、冗余和补偿造成的混乱 用标准方法进行调查。我们最常见的策略是配对生物传感器，以可视化 用精确的工具控制活细胞中这些过程的调控 行为。对于细胞迁移，我们正在将复杂的定向移动过程分解为其 基本要素-细胞如何决定启动突起，突起的形状如何指定， 突起如何相互竞争以实现细胞极性，以及这一过程如何受到 外部渐变。对于T细胞的激活，我们正在研究细胞如何将微小的抗原差异转化为 通过利用光响应性T细胞抗原结合到细胞激活的大变化。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 转录因子动力学规定了基因激活的模式。

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.