Cellular Decision Making

细胞决策

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/10414972
• 关键词: Address; Antigens; Atherosclerosis; Autoimmune Diseases; Behavior; Biosensor; Cell Polarity; Cells; Cellular biology; Complex; Decision Making; Enhancers; Feedback; Financial compensation; Gene Activation; Immunotherapy; Inflammation; Investigation; Light; Logic; Lymphocyte; Molecular; Movement; Mus; Neoplasm Metastasis; Organism; Pathologic Processes; Pattern; Peptides; Process; Property; Science; Sea; Shapes; Signal Transduction; Specific qualifier value; System; T-Cell Activation; T-Lymphocyte; Testing; Transcriptional Activation; Work; antigen binding; base; cancer therapy; cell behavior; cell motility; cell type; embryonic stem cell; immune activation; neutrophil; optogenetics; promoter; tool; transcription factor; vaccine development

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.

项目概要/摘要 我的实验室致力于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过程中发展而来 分子到生命系统的新兴特性。我们目前关注三个问题：如何 中性粒细胞控制它们的形状和运动，淋巴细胞如何检测自我海洋中的稀有外来肽 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 类型和行为使得更容易识别细胞决策的一般原则 给定系统的细节。并且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。变革性科学经常发生在界面上，因此我们寻求借用工具和概念 其他领域来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 以加快进度。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，以规避反馈、冗余和补偿的方式，这些反馈、冗余和补偿会混淆 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 活细胞中这些过程的定量动力学，用精密工具来控制这些过程的调节器 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出物，如何指定突出物的形状， 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以下因素的影响： 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 T 细胞抗原来结合细胞激活的巨大变化。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 转录因子动力学指定了基因激活的模式。