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Systems Biology of Collective Cell Decisions

集体细胞决策的系统生物学

基本信息

批准号：
8743222
负责人：
JAMES E. FERRELL
金额：
$ 204.32万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-30 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8743222
关键词：
Actins Adipocytes Back Biological Biology Biosensor CDK2 gene Cell Cycle Cell Cycle Regulation Cell Density Cell Differentiation process Cell Proliferation Cells Chemicals Communities Complement Complex Computing Methodologies Cytoplasmic Granules Data Set Decision Making Development Disease Drosophila genus Education Educational process of instructing Embryo Employee Strikes Endothelial Cells Ensure Epithelial Cells Feedback Fingers Goals Human Image In Vitro Individual Laboratories Lead Learning Life Malignant Neoplasms Mechanics Mediating Microfluidics Microscopy Modeling Molecular Nerve Degeneration Neurons Outcome Postdoctoral Fellow Process Regulation Research Research Activity Research Personnel Rest System Systems Biology Technology Tertiary Protein Structure Testing Time Training Umbilical vein Wing Work Xenopus laevis base cell behavior cell motility cellular imaging data modeling design experience graduate student imaging modality induced pluripotent stem cell innovation insight migration new technology novel outreach public health relevance reconstitution research study sensor two-dimensional

项目摘要

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.

描述(由申请人提供)：该中心的首要目标是为细胞决策提供系统级的理解，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各种模型。该中心包括一个研究部分，包括三个协同项目，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训研究生和博士后研究员。我们还将开展外展工作，传播数据集和模型，并邀请研究人员参加斯坦福大学的暑期课程以及系统生物学培训。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，重点关注非洲爪哇胚胎和原代人脐静脉内皮细胞的集体细胞增殖。我们理解集体细胞迁移的努力将集中在集体迁移的力学模型上，该模型基于对力在二维细胞片中的传播的新见解。在我们理解集合性细胞分化的第三个努力中，我们将以人诱导多能干细胞(IPS)、颗粒神经元前体(GNP)、脂肪细胞和果蝇翅膀上皮细胞为模型，重点学习细胞从增殖状态到分化状态的集体转换规则。由于相邻细胞倾向于以一种相关的方式分化，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，来寻求了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。被调查的生物项目共享共同的监管设计，增加了显著的协同效应，将加强变化，即拟议的中心将取得重大新进展。