Interplay between signaling and noise in cellular decision making

细胞决策中信号传导和噪声之间的相互作用

• 批准号: 9050691
• 负责人: Casim Sarkar
• 金额: $ 34.55万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-08 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9050691
• 关键词: Affect; Biochemical Reaction; Biological; Biological Models; Cell Differentiation process; Cells; Communicable Diseases; Computational Biology; Computer Simulation; Cues; Decision Making; Engineering; Epidermal Growth Factor; Erythropoietin; Feedback; Future; Health; Hematopoiesis; Hematopoietic stem cells; Heterogeneity; Individual; Life; Malignant Neoplasms; Mitogen-Activated Protein Kinases; Modeling; Myelogenous; Nerve Growth Factors; Noise; Outcome; PC12 Cells; Phosphotransferases; Play; Population; Process; Public Health; Regenerative Medicine; Role; Signal Transduction; Signaling Molecule; Stem cells; Systems Biology; Theoretical Studies; Thrombopoietin; Tissues; Work; Yeasts; base; cellular engineering; cellular imaging; improved; in vivo; insight; neurogenesis; progenitor; research study; stem; synthetic biology; transcription factor; transdifferentiation

 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.

 描述（由适用提供）：细胞决策制定的经典观点是，单个单元基于以环境和细胞内信号的形式根据向其提供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，生物学噪声通常是由于继承在生化反应中的随机性或细胞机械变异性引起的，CA通常在影响细胞脂肪结果的关键作用。在此提案中，我们检查了信号和噪声在细胞分化中的相互联系的作用，并假设细胞信号传导分子中的噪声可以从一个细胞状态到另一个细胞状态产生全新的轨迹。我们将使用计算和合成生物学方法来了解这种轨迹的出现，并将使用系统生物学方法在实验中证明和操纵这些轨迹在神经发生和造血模型中。我们的研究结果将对细胞决策的基本机制（尤其是在分化中）产生更深入的见解，并应允许STEM和祖细胞在再生医学中的应用中进行更强大的工程。