Mathematical modeling of cellular signaling systems

该项目寻求整合计算方法，包括数学建模和图像 分析技术，以及理解复杂细胞的定量实验方法 行为。特别是，我们研究细胞的过程，如细胞命运的决定，极性 建立和梯度感应，由细胞内信号网络协调。目标是 我们研究的重点是了解这些网络如何作为集成系统发挥作用。数学 需要建模以了解协调 信号通路的时空动力学，需要计算图像分析来提取 来自活细胞图像的定量信息，这是告知和验证模型所需的。 我们用来研究细胞信号的主要模式生物是酿酒酵母。我们的 研究结合微流控技术和活细胞显微镜观察细胞行为 控制良好的环境。这项工作是与我们长期合作的实验室一起完成的 合作者Beverly Errede博士、Daniel Lew和Henrik Dohlman博士。实验室中已建立的项目 包括：1)了解细胞极性和梯度感应的分子机制；2) 识别动态调节基因表达和命运决定的信号基序。一场激动人心的 该实验室的新方向是研究衰老对细胞信号的影响。我的实验室还参与了 合作项目，以研究哺乳动物细胞中的细胞信号以及如何调节失调 这些途径会导致人类疾病。目前实验室中的项目包括：1)一个长期的 与理查德·鲍彻博士合作了解嘌呤能信号如何维持呼吸道表面 囊性纤维化的液体动态平衡和失调，2)与我们建立的一个新项目 合作者Klaus Hahn博士了解吞噬过程中协调信号的机制 3)与奈德·夏普莱斯博士合作的一个新项目，旨在了解调控细胞的机制 造血过程中的分化。所有这些项目的统一主题是使用数学 建模以了解反馈和前馈监管如何产生协调 时空行为。我们调查的最终目标是生成真正的预测性模型 体内细胞过程，可应用于新治疗策略的基本设计。 好了！

This project seeks to integrate computational methods, including mathematical modeling and image analysis techniques, with quantitative experimental approaches to understand complex cellular behavior. In particular, we investigate cellular processes, such as cell fate decisions, polarity establishment, and gradient sensing, that are coordinated by intracellular signaling networks. The goal of our research is to understand how these networks function as integrated systems. Mathematical modeling is needed to understand the feedback and feed forward regulation that coordinates the spatiotemporal dynamics of signaling pathways, and computational image analysis is needed to extract the quantitative information from live-cell images that is required to inform and validate the models. The primary model organism we use to study cell signaling is the yeast Saccharomyces cerevisiae. Our investigations combine microfluidic technology with live-cell microscopy to observe cellular behavior in well-controlled environments. This work is performed together with the labs of our longstanding collaborators Drs. Beverly Errede, Daniel Lew and Henrik Dohlman. Established projects in the lab include: 1) understanding molecular mechanisms involved in cell polarity and gradient sensing and 2) identifying signaling motifs that dynamically regulate gene expression and fate decisions. An exciting new direction for the lab is to investigate the effects of aging on cell signaling. My lab is also involved in collaborative projects to investigate cell signaling in mammalian cells and how the dysregulation of these pathways leads to human disease. Current projects in the lab include: 1) a longstanding collaboration with Dr. Richard Boucher to understand how purinergic signaling maintains airway surface liquid homeostasis and is dysregulated in cystic fibrosis, 2) a new project with our established collaborator Dr. Klaus Hahn to understand mechanisms that coordinate signaling during phagocytosis and 3) a new project with Dr. Ned Sharpless to understand the mechanisms that regulate cell differentiation during hematopoiesis. The unifying theme of all these projects is the use of mathematical modeling to understand how feedback and feed forward regulation generates coordinated spatiotemporal behavior. The ultimate goal of our investigations is to generate truly predictive models of in vivo cellular processes that can be applied to the rationale design of new therapeutic strategies. !