CAREER: Multiscale Model for Cell Morphogenesis and Tissue Development in Plant Leaves

职业：植物叶片细胞形态发生和组织发育的多尺度模型

• 批准号: 2338630
• 负责人: Weitao Chen
• 金额: $ 49.81万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-07-01 至 2029-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2338630&HistoricalAwards=false
• 关键词: CAREER; Multiscale; Model; Cell; Morphogenesis

This study will improve our understanding about general mechanisms involved in cell morphogenesis. Epidermal cells in plant leaves, especially pavement cells (PCs), exhibit interdigitated puzzle shapes. Shape formation of PCs serves as an ideal model to understand principles governing cell morphogenesis and tissue growth in developmental biology. During the development, PCs change from small rounded polygonal shapes into large interdigitated puzzle shapes, under the regulation of the extracellular plant hormone and multiple key molecules accumulated at the plasma membrane (PM). This developmental process also involves reorganization of cytoskeletal components and dynamic cell-to-cell communication. The multiscale mathematical model proposed in this research will have a broad range of applications from tissue engineering to biomanufacturing and biotechnology. The PI will develop a satellite undergraduate research program based on University of California, Riverside (UCR), a Hispanic-serving institution with many first generation college students. The program will also recruit students from California State Universities and high schools in local public school district. Research symposia and summer research programs will be organized through the coordination with department of mathematics, Association of Women in Mathematics at UCR Chapter, Interdisciplinary Center for Quantitative Modeling in Biology at UCR, and nearby colleges to promote public awareness on research and career paths in mathematical biology.The morphogenesis of PCs is a complex process. During the early stage, extracellular hormone induces nanoclustering on the PM of individual cells to initiate cell polarization. It is followed by nonhomogeneous mechanical forces exerted along cell wall and a subcellular signaling gradient to regulate cell-cell interaction. Stable cell polarization, further the interdigitated jigsaw cell shapes, will be established under the regulations between the nanoclustering signals and structural components in the same cell and regulations of Rho GTPase signals between neighboring cells. Different hypotheses have been proposed for the mechanism underlying the PC morphogenesis, while most of them focus on either chemical signals or mechanical properties in PCs. The proposed study will test new hypotheses that include both the chemical signaling network and mechanical properties, as well as interactions between them, and therefore provide novel insights into the fundamental principles of cell shape formation and tissue development. This project will develop a multiscale model using the local level set method to incorporate both chemical signals and mechanical properties in a multicellular environment to test different hypotheses on the shape formation of PCs. Machine learning techniques and experimental data will be used in the modeling selection, parameter estimation and model calibration.This CAREER project is jointly funded by the Mathematical Biology Program at the Division of Mathematical Science and the Developmental Systems Cluster at the Division of Integrative Organismal Systems in the Directorate for Biological Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这项研究将提高我们对涉及细胞形态发生的一般机制的理解。植物叶片中的表皮细胞，尤其是人行道细胞（PC），表现出互连的拼图形状。 PC的形状形成是理想的模型，以了解发育生物学中细胞形态发生和组织生长的原理。在开发过程中，PC从小的圆形多边形形状变为大型互相的拼图形状，在调节细胞外植物激素和质膜上积累的多个关键分子（PM）下。这种发育过程还涉及重组细胞骨架成分和动态细胞间通信。这项研究中提出的多尺度数学模型将具有从组织工程到生物制造和生物技术的广泛应用。 PI将根据加利福尼亚大学河滨分校（UCR）制定卫星本科研究计划，这是一家西班牙裔服务机构，拥有许多第一代大学生。该计划还将招募当地公立学区的加利福尼亚州立大学和高中的学生。研究研讨会和夏季研究计划将通过与数学系，UCR分会的数学女性协会，UCR跨学科定量建模中心和附近大学的协调组织，以促进公众对数学生物学研究和职业道路的认识。在早期，细胞外激素会在单个细胞的PM上诱导纳米簇启动细胞极化。接下来是沿细胞壁施加的非均匀机械力，并具有亚细胞信号传导梯度以调节细胞 - 细胞相互作用。稳定的细胞极化，进一步的夹具拼图细胞形状将在同一细胞中的纳米簇信号与结构成分之间的规定与相邻细胞之间Rho GTPase信号的法规之间建立。已经提出了针对PC形态发生的机制的不同假设，而大多数则集中在PC中的化学信号或机械性能上。拟议的研究将测试包括化学信号网络和机械性能在内的新假设，以及它们之间的相互作用，从而提供了对细胞形状形成和组织发展的基本原理的新见解。该项目将使用局部水平集方法开发多尺度模型，以在多细胞环境中同时合并化学信号和机械性能，以测试对PC形成形成的不同假设。 Machine learning techniques and experimental data will be used in the modeling selection, parameter estimation and model calibration.This CAREER project is jointly funded by the Mathematical Biology Program at the Division of Mathematical Science and the Developmental Systems Cluster at the Division of Integrative Organismal Systems in the Directorate for Biological Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader影响审查标准。