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Cellular Decision Making

细胞决策

基本信息

批准号：
10414972
负责人：
Orion D Weiner
金额：
$ 91.7万
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.

项目总结/摘要我的实验室试图定义复杂细胞行为的分子逻辑-细胞如何从一组相互作用的分子到生命系统的涌现特性。我们目前关注三个问题：嗜中性粒细胞控制它们的形状和运动，淋巴细胞如何在大量的自身免疫系统中检测到罕见的外源肽，肽，以及小鼠胚胎干细胞如何调节转录激活。研究多种细胞类型和行为使得更容易识别细胞决策的一般原则，特定系统的细节。它为不同项目之间的交叉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，其他领域解决细胞生物学中的悬而未决的问题，并在需要时经常开发新工具来加速进展。例如，光遗传学使我们能够插入定义的信号节点，并测试子电路的一种逻辑，以避免反馈、冗余和补偿的方式，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，这些过程在活细胞中的定量动力学与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部分-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电池极性，以及该过程如何被外部梯度对于T细胞活化，我们正在研究细胞如何将抗原的微小差异转化为通过利用光响应性T细胞抗原结合细胞活化的大变化。最后，我们研究转录激活的逻辑，特别是增强子如何激活启动子，转录因子动力学指定了基因激活的模式。