CAREER: The Landscape of Differentiation: Understanding the Mesenchymal Stem Cell Response to the Topography and Geometry of their Environment

职业：分化景观：了解间充质干细胞对其环境的地形和几何形状的反应

• 批准号: 1151454
• 负责人: Ashok Prasad
• 金额: $ 42.32万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1151454&HistoricalAwards=false
• 关键词: CAREER; Landscape; Differentiation; Understanding; Mesenchymal

The goal of this research project is to develop a causal mechanistic understanding of the response of bone marrow stromal cells (MSCs) to the topography of the surfaces that they are cultured on, utilizing mathematical models and experiments. While the primary focus is on MSCs, many of the questions being addressed are relevant to other mammalian cells. Theoretical models will be developed of cell spreading, adhesion and cell shape on smooth surfaces and on nano-patterned surfaces. Computational signaling models will be built that uncovers the linkages between cell shape and the differentiation decision of MSCs. Experiments in collaborating laboratories will facilitate model development and model validation.The project will help understand how the physical properties of the tissues themselves affect tissue maintenance (or homeostasis) through modulation of the differentiation decision of multipotent stem cells. This may be the process by means of which the extra-cellular matrix helps shape tissues. An understanding of these processes is currently lacking, and this research seeks to help fill this gap. The project will yield new insights into tissue homeostasis and development via the development of biophysical models of cells in different environments, which integrates the interactions and the feedback between the environment, the cellular cytoskeleton and signaling. The research program offers support for training graduate students, undergraduate students, school students and K-12 teachers. The main educational goal of the PI is teaching and disseminating modeling methods for biology and ecology to students at different levels, from school students to graduate students. The PI will develop an undergraduate-level course on modeling methods in biology, and incorporate research carried out in his laboratory, as well as current research from the world over, in the syllabus. Apart from training graduate students in his laboratory, the PI will offer undergraduate students and incoming freshmen, especially students from underrepresented minorities, an opportunity to participate in summer research. In collaboration with the Education and Outreach Center of the College of Natural Sciences (EOC-CNS) at CSU, the PI will develop course material and hold workshops to train K-12 teachers in the art and science of building computational models to understand complex biological and ecological phenomena using free online tools such as Netlogo. This will also be applied to ongoing K-12 projects that the EOC-CNS is currently involved. The EOC-CNS will help design the workshops, recruit teachers especially those who teach under-represented minorities, and will also help evaluate the impact of the workshops by a professional evaluator. K-12 teachers attending the workshop will be trained to incorporate computational models into their teaching, as well as into school research activity. Workshops will also be offered directly to school students, in collaboration with K12 teachers, during summer STEM camps organized by schools in Fort Collins. The emphasis will be on exploiting modeling tools such as Netlogo to make and visualize simple models that give insight into complicated phenomena, involving nonlinearity, stochasticity, feedback and synchronization. Examples will be taken from ecology and biology, and especially on modeling phenomena that K-12 students will encounter in their classes.

该研究项目的目的是对利用数学模型和实验的骨髓基质细胞（MSC）对骨髓基质细胞（MSC）的反应进行因果机械理解。虽然主要的重点是MSC，但要解决的许多问题与其他哺乳动物细胞有关。理论模型将在光滑表面和纳米图案表面上的细胞扩散，粘附和细胞形状开发。将建立计算信号模型，以发现细胞形状与MSC的分化决策之间的联系。合作实验室的实验将有助于模型开发和模型验证。该项目将通过调节多能干细胞的分化决策来帮助了解组织本身如何影响组织维持（或稳态）。这可能是细胞外基质有助于塑造组织的过程。目前缺乏对这些过程的理解，这项研究旨在帮助填补这一空白。该项目将通过开发不同环境中细胞的生物物理模型来对组织稳态和发育产生新的见解，从而整合了环境，细胞细胞骨架和信号传导之间的相互作用和反馈。该研究计划为培训研究生，本科生，学校学生和K-12老师提供支持。 PI的主要教育目标是向不同级别的学生教授生物学和生态学的建模方法，从学校学生到研究生。 PI将开发有关生物学建模方法的本科课程，并纳入其实验室中进行的研究，以及全球目前的研究中的研究。除了他的实验室培训研究生外，PI还将为本科生和新生，尤其是来自代表性不足少数群体的学生提供，这是参加夏季研究的机会。与CSU的自然科学学院（EOC-CNS）的教育和外展中心合作，PI将开发课程材料，并举办研讨会，以培训K-12教师在构建计算模型的艺术和科学上，以了解使用NetLogo等免费在线工具的复杂生物学和生态现象。这也将应用于EOC-CNS目前涉及的正在进行的K-12项目。 EOC-CNS将帮助设计研讨会，招募教师，尤其是那些教授代表性不足的少数民族的教师，还将帮助评估专业评估员的研讨会的影响。 参加研讨会的K-12教师将接受培训，以将计算模型纳入其教学以及学校研究活动中。在柯林斯堡学校组织的夏季STEM营地期间，还将与K12老师合作，​​直接向学校学生提供讲习班。重点将是利用Netlogo之类的建模工具来制作和可视化简单的模型，从而深入了解复杂现象，涉及非线性，随机性，反馈和同步。例子将来自生态学和生物学，尤其是在建模K-12学生在课堂上会遇到的现象。