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个体细胞基于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已经明确表明，生物噪声，通常产生于内在的随机性在潜在的生化反应或变异的细胞机器，可以经常发挥关键作用，影响细胞命运的结果。在这个提议中，我们研究了信号和噪声在细胞分化中的相互作用，我们假设细胞信号分子中的噪声可以产生从一个细胞状态到另一个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了解这些轨迹可能会出现，我们将使用系统生物学的方法来实验证明和操纵这些轨迹在模型系统的神经发生和造血。我们的研究结果将对细胞决策的基本机制产生更深入的了解，特别是在分化方面，并且应该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.