Interplay between signaling and noise in cellular decision making

 描述(由申请人提供)：细胞决策的经典观点是，单个细胞根据以环境和细胞内信号的形式呈现给它们的信息做出可预测的选择。然而，最近的理论和实验研究明确表明，生物噪声通常由潜在生化反应的固有随机性或细胞机械的可变性引起，通常在影响细胞命运的结果中发挥关键作用。在这个提议中，我们研究了信号和噪声在细胞分化中相互关联的作用，并假设细胞信号分子中的噪声可以产生从一种细胞状态到另一种细胞状态的全新轨迹。我们将使用计算和合成生物学的方法来理解这些轨迹是如何产生的，我们将使用系统生物学的方法在神经发生和造血的模型系统中实验地演示和操纵这些轨迹。我们的研究结果将对细胞决策的基本机制有更深入的了解，特别是在分化方面，并应允许更强大的干细胞和祖细胞工程在再生医学中的应用。

 DESCRIPTION (provided by applicant): The classical view of cellular decision making is that individual cells make predictable choices based on the information presented to them in the form of both environmental and intracellular signals. However, recent theoretical and experimental studies have unambiguously shown that biological noise, typically arising from inherent stochasticity in underlying biochemical reactions or variability in cellular machinery, ca often play a crucial role in influencing cell fate outcomes. In this proposal, we examine the interconnected roles of signaling and noise in cell differentiation and we hypothesize that noise in cell signaling molecules can engender entirely new trajectories from one cell state to another. We will use computational and synthetic biology approaches to understand how such trajectories may arise, and we will use systems biology approaches to experimentally demonstrate and manipulate these trajectories in model systems of neurogenesis and hematopoiesis. The results of our study will yield deeper insights into the fundamental mechanisms underlying cellular decision making, particularly in differentiation, and should allow for more robust engineering of stem and progenitor cells for applications in regenerative medicine.