CAREER: Modelling Emergent Behaviour of Gene Networks Controlling Plant Stem Cells

职业：模拟控制植物干细胞的基因网络的突发行为

• 批准号: 1453130
• 负责人: Rosangela Sozzani
• 金额: $ 74.1万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1453130&HistoricalAwards=false
• 关键词: CAREER; Modelling; Emergent; Behaviour; Gene

Climate uncertainty, a growing scarcity of arable land, and the potential to develop renewable sources of bioenergy all focus our attention on the degree to which we depend on plants. One key to improving plant productivity is to understand better the control of their growth and development. Plants possess stem cells, whose division and differentiation is central to plant growth and the building of new organs. Current understanding of plant stem cell regulation does not address well the complex networks of regulation that are involved. This project will use the model plant Arabidopsis to experimentally identify the essential features that govern stem cell regulatory networks in the developing root, and will develop accurate mathematical models that describe the behaviour of these networks. The root captures nutrients essential to the plant, and knowledge of the rules controlling root stem cell behaviour will facilitate the future development of plants for crop improvement. The project will provide cross-training and education to students through the development of courses at the interface between plant biology and bioengineering. These courses will be tailored to the needs of a diverse target audience. The research team will engage a wider audience, ranging from K-12 students to adults, to inform the public on important issues including plant stem cells, plant bioengineering, and crop improvement. A key to systems-level understanding of the molecular mechanisms regulating stem cells is the ability to analyse the dynamics of networks in the context of a living organism. Identifying the essential features that govern stem cell regulatory networks and their emergent behaviours will contribute to an accurate understanding of the design rules governing cell pluripotency. This project integrates techniques derived from biological, mathematical, and engineering science to elucidate mechanisms that regulate plant stem cell fate and maintenance. The project's foundation will be based on the transcriptional profile of two Arabidopsis root stem cell populations, the cortex/endodermal initials (CEI) and xylem (XYL), as well as the quiescent centre cells that maintain the stem cells in their undifferentiated status. Bayesian modelling of transcriptional dynamics, and perturbation testing of the models, have revealed TARGET OF MONOPTEROS3 (TMO3) to be a key regulator of both CEI and XYL stem cells. Novel imaging techniques have been developed that will enable quantitative measurements of diffusion, concentration, and interactions of molecular factors responsible for signalling between stem cells. By integrating these data with mathematical modelling, the project will achieve an improved understanding of how stem cell division is precisely regulated in space and time. The project's research goals are to: 1) characterize the transcriptional signature responsible for stem cell regulation and to test the hypothesis that interacting transcriptional networks operate across different stem cells; and 2) generate mathematical models that incorporate spatial and temporal information to describe communication between stem cells. After determining which parameters are critical to generate a robust mathematical model, models will be generated that describe how regulator signals are propagated between and among cells, and will identify perturbations capable of resetting decision-making signals. These efforts will provide a framework for comparing stem cell development in plants and animals, and will contribute to future plant breeding efforts in the face of climate uncertainty.

气候的不确定性、可耕地的日益稀缺，以及开发可再生生物能源的潜力，都把我们的注意力集中在我们对植物的依赖程度上。提高植物生产力的一个关键是更好地了解它们的生长和发育的控制。植物拥有干细胞，干细胞的分裂和分化对植物生长和新器官的形成至关重要。目前对植物干细胞调控的理解并没有很好地解决所涉及的复杂调控网络。该项目将使用模式植物拟南芥实验确定在发育中的根中控制干细胞调节网络的基本特征，并将开发描述这些网络行为的精确数学模型。根捕获植物必需的营养物质，了解控制根干细胞行为的规则将促进未来植物的发展，以改善作物。该项目将通过开发植物生物学和生物工程之间的交叉课程，为学生提供交叉培训和教育。这些课程将根据不同目标受众的需要量身定制。研究小组将吸引更广泛的受众，从K-12学生到成年人，向公众介绍包括植物干细胞、植物生物工程和作物改良在内的重要问题。对调节干细胞的分子机制的系统级理解的关键是分析活生物体背景下网络动力学的能力。识别控制干细胞调控网络及其紧急行为的基本特征将有助于准确理解控制细胞多能性的设计规则。该项目整合了生物、数学和工程科学的技术，以阐明调节植物干细胞命运和维持的机制。该项目的基础将基于两个拟南芥根干细胞群体的转录谱，皮质/内胚层首细胞（CEI）和木质部（XYL），以及维持干细胞处于未分化状态的静止中心细胞。转录动力学的贝叶斯模型和模型的扰动测试表明，TMO3是CEI和XYL干细胞的关键调节因子。新的成像技术已经开发出来，可以定量测量干细胞之间信号传导的分子因子的扩散、浓度和相互作用。通过将这些数据与数学建模相结合，该项目将更好地理解干细胞分裂是如何在空间和时间上精确调节的。该项目的研究目标是：1)表征负责干细胞调控的转录特征，并测试相互作用的转录网络在不同干细胞之间运作的假设；2)生成包含空间和时间信息的数学模型来描述干细胞之间的交流。在确定哪些参数对于生成稳健的数学模型至关重要之后，将生成描述调节信号如何在细胞之间和细胞之间传播的模型，并将识别能够重置决策信号的扰动。这些努力将为比较植物和动物的干细胞发育提供一个框架，并将有助于未来面对气候不确定性的植物育种工作。