CAREER:Functional Heterogeneity in Cell Chemotaxis

职业：细胞趋化性的功能异质性

• 批准号: 1055502
• 负责人: Cynthia Reinhart-King
• 金额: $ 40万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-15 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1055502&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针对细胞迁移的综合研究和教育计划。 该奖项在国家科学基金会的CBET部门的支持下，将使开发新工具开发，以揭示有关内皮细胞趋化性的机制。研究和教育将通过他们共同关注细胞 - 托管基质相互作用来整合。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。人群内的自然细胞对细胞变化和异质性将被利用，以发现基本机制，这些机制可响应血管内皮生长因子（VEGF），从而驱动内皮细胞中有效的趋化性。将开发出一种新型的趋化装置，该装置基于其对VEGF趋化梯度的响应的稳健性，对内皮细胞进行分类。这些亚种群将进行分析，以分析有助于差异趋化行为的基本分子差异。 实验将在2D和3D微环境中进行，并进行比较。 这项工作有可能发现对内皮细胞趋化性分子调节的关键见解。 此外，它在组织工程领域具有明显的影响，在组织工程领域中，受控的，有向的内皮细胞迁移可以使组织工程脚手架的血管网络的工程以及癌症研究的工程，在这种研究中，对血管生成的更好理解可以使更具靶向靶向的治疗剂的发展能够开发更靶向的治疗剂，从而防止内皮细胞趋化的趋化性反应。 该职业计划的更广泛的影响是开发跨学科学习环境，该环境将生物学和工程跨多个长度（分子，细胞和组织水平）联系起来。 创新的教学方法和外展活动将采用以可行的方式引入本地，服务不足的农村社区中的中学和高中女生，以介绍生物学和工程学的概念，并促进科学领域的终身学习。