CAREER:Functional Heterogeneity in Cell Chemotaxis

职业：细胞趋化性的功能异质性

• 批准号: 1741588
• 负责人: Cynthia Reinhart-King
• 金额: $ 2.6万
• 依托单位: Vanderbilt University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1741588&HistoricalAwards=false
• 关键词: CAREER; Functional; Heterogeneity; Cell; Chemotaxis

The overall goal of this proposal is to develop an integrated research and educational plan focused on cellular migration. This award, supported by the CBET division of the National Science Foundation, will enable the development of novel tools to uncover the mechanisms governing endothelial cell chemotaxis. Research and education will be integrated through their common focus on cell-extracellular matrix interactions. The research goal of this proposal is to use an approach inspired by directed evolution to study chemotaxis. The natural cell-to-cell variations and heterogeneities within a population will be exploited to uncover basic mechanisms that drive efficient chemotaxis in endothelial cells in response to vascular endothelial growth factor (VEGF). A novel chemotactic device will be developed which sorts endothelial cells based on the robustness of their response to chemotactic gradients of VEGF. These sub-populations will be analyzed for underlying molecular differences that are contributing to the differential chemotactic behaviors. Experiments will be performed in both 2D and 3D microenvironments and compared. This work has the potential to uncover critical insights into the molecular regulation of endothelial cell chemotaxis. Moreover, it has clear implications in the field of tissue engineering, where controlled, directed endothelial cell migration could enable the engineering of vascular networks in tissue engineered scaffolds, and in cancer research, where a better understanding of angiogenesis could enable the development of more targeted therapeutics to prevent endothelial cell chemotactic response. The broader impact of this CAREER program is the development of an interdisciplinary learning environment that connects biology and engineering across multiple length scales (molecular, cellular and tissue level). Innovative teaching methodologies and outreach activities will be employed to introduce middle and high school girls in the local, underserved, rural community to concepts in biology and engineering in a tractable way and to promote lifelong learning in science.

该提案的总体目标是制定一项专注于细胞迁移的综合研究和教育计划。 该奖项由美国国家科学基金会 CBET 部门支持，将有助于开发新工具来揭示内皮细胞趋化性的调控机制。研究和教育将通过对细胞与细胞外基质相互作用的共同关注来整合。该提案的研究目标是使用受定向进化启发的方法来研究趋化性。将利用群体内的自然细胞间变异和异质性来揭示驱动内皮细胞响应血管内皮生长因子（VEGF）而有效趋化的基本机制。将开发一种新型趋化装置，根据内皮细胞对 VEGF 趋化梯度反应的稳健性对内皮细胞进行分类。将分析这些亚群的潜在分子差异，这些差异导致不同的趋化行为。 实验将在 2D 和 3D 微环境中进行并进行比较。 这项工作有可能揭示内皮细胞趋化性分子调节的重要见解。 此外，它在组织工程领域具有明显的意义，在组织工程领域，受控、定向的内皮细胞迁移可以实现组织工程支架中血管网络的工程设计；在癌症研究中，更好地了解血管生成可以帮助开发更有针对性的治疗方法，以防止内皮细胞趋化反应。 该职业计划的更广泛影响是开发跨学科学习环境，将生物学和工程学跨多个长度尺度（分子、细胞和组织水平）连接起来。 将采用创新的教学方法和外展活动，以易于处理的方式向当地服务水平低下的农村社区的初中和高中女孩介绍生物学和工程学的概念，并促进科学的终身学习。