CAREER:Functional Heterogeneity in Cell Chemotaxis

该提案的总体目标是制定一个集中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，将使开发新的工具来揭示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-细胞外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。将利用群体内的天然细胞间变异和异质性来揭示响应于血管内皮生长因子（VEGF）而驱动内皮细胞中的有效趋化性的基本机制。将开发一种新的趋化装置，其基于内皮细胞对VEGF趋化梯度的反应的稳健性来对内皮细胞进行分类。将分析这些亚群中导致差异趋化行为的潜在分子差异。 实验将在2D和3D微环境中进行并进行比较。 这项工作有可能揭示关键的见解内皮细胞趋化性的分子调控。 此外，它在组织工程领域具有明确的意义，其中受控的、定向的内皮细胞迁移可以使组织工程支架中的血管网络工程化，并且在癌症研究中，更好地理解血管生成可以使更有针对性的治疗剂的开发能够防止内皮细胞趋化反应。 这个职业计划的更广泛的影响是跨学科学习环境的发展，跨多个长度尺度（分子，细胞和组织水平）连接生物学和工程学。 将采用创新的教学方法和推广活动，以易于掌握的方式向当地服务不足的农村社区的初中和高中女生介绍生物学和工程学概念，并促进科学方面的终身学习。

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.