Systems Biology of Collective Cell Decisions

描述（由申请人提供）：该中心的首要目标是提供一个系统级的理解细胞的决策，重点是细胞增殖，迁移和分化的相互关联的过程。特别是，我们将专注于如何开发和验证从分子单细胞机制到集体细胞行为的模型。该中心包括三个协同项目的研究部分，核心将丰富斯坦福大学的系统生物学研究，以及一个教育部分，重点是在这个新兴的新领域培养研究生和博士后研究员。我们还将开展外联工作，传播数据集和模型，并邀请研究人员参加暑期课程，以及在斯坦福大学接受系统生物学培训。 在拟议的研究中，我们将专注于集体细胞增殖，专注于非洲爪蟾胚胎和原代人脐静脉内皮细胞，使用参与实验室开发的新型生物传感器。我们理解集体细胞迁移的努力将集中在集体迁移的力学模型上，该模型基于对二维细胞片中力的传播的新见解。在我们理解集体细胞分化的第三次努力中，我们将重点学习细胞集体从增殖状态转变为分化状态的规则，使用人类诱导多能干细胞（IPS），颗粒神经元前体细胞（GNP），脂肪细胞和果蝇翅膀上皮细胞作为模型。由于相邻细胞倾向于以相关的方式分化，我们将通过测试分泌因子和直接细胞接触是否有助于集体分化决定来寻求理解细胞如何协调分化。这些研究工作将得到加强 开发新的扰动和生物传感器技术，使我们能够验证这些过程的模型。被调查的生物项目具有共同的监管设计，增加了显著的协同作用，这将增强拟议中心将取得重大新进展的变化。

DESCRIPTION (provided by applicant): The overarching aim of the Center is to provide a systems-level understanding for cellular decision-making focusing on the interrelated processes of cell proliferation, migration, and differentiation. Particularly, we will be focusing on how to develop and validate models that range from molecular single cell mechanisms to collective cell behavior. The center includes a research component with three synergistic projects, cores that will enrich systems biology research in Stanford, as well as an education component focusing on training graduate student and postdoctoral fellows in this emerging new field. We will also have an outreach effort to disseminate data sets and models and to invite researchers to participate in summer courses as well as to train in systems biology in Stanford. In the proposed research, we will focus on Collective Cell Proliferation by focusing on Xenopus laevis embryos and on primary human umbilical vein endothelial cells using novel biosensors developed in the participating laboratories. Our effort to understand Collective Cell Migration wil focus on mechanical models for collective migration based on novel insights into the propagation of force in 2-dimensional cell sheets. In our third effort to understand Collective Cel Differentiation we will be focusing on learning the rules by which cells collectively transition from proliferative to differentiated states using human induced pluripotent stem (IPS) cells, granule neuron precursors (GNP), adipocytes, and drosophila wing epithelial cells as models. Since neighboring cells tend to differentiate in a correlated fashion, we will seek to understand how cells coordinate differentiation by testing whether secreted factors and direct cell contact contribute to collective differentiation decisions. These research efforts will be augmented by the development of new perturbation and biosensor technologies that will enable us to validate models for these processes. The investigated biological projects share common regulatory designs, adding significant synergies that will enhance the change that significant new advances will be made in the proposed Center.