Systems Biology of Collective Cell Decisions

描述（由申请人提供）：中心的总体目标是为细胞决策提供系统级的理解，重点关注细胞增殖、迁移和分化的相关过程。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。该中心包括一个具有三个协同项目的研究部分，这些项目将丰富斯坦福大学的系统生物学研究，以及一个专注于培养这一新兴领域的研究生和博士后的教育部分。我们还将努力推广数据集和模型，并邀请研究人员参加斯坦福大学的暑期课程和系统生物学培训。在拟议的研究中，我们将利用参与实验室开发的新型生物传感器，通过聚焦非洲爪蟾胚胎和原代人脐静脉内皮细胞，专注于集体细胞增殖。我们理解集体细胞迁移的努力将集中在集体迁移的机械模型上，该模型基于对二维细胞片中力传播的新见解。在我们理解集体细胞分化的第三项努力中，我们将重点学习细胞集体从增殖状态过渡到分化状态的规则，使用人类诱导多能干细胞（IPS）细胞、颗粒神经元前体（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，试图了解细胞如何协调分化。这些研究工作将由

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.