CAREER: Flow Modulation of Receptor-Mediated Polymorphonuclear Leukocyte-Tumor Cell Interactions: A Research and Education Program

PI的目标是：(1)研究PMN-肿瘤细胞聚集形成的动力学作为剪切速率的函数，以及PMN/肿瘤细胞激活状态。这些数据将使用基于Smoluchowski的两体碰撞理论的数学模型进行分析，该模型将提供称为粘附效率的重要细胞特性的数值估计，这反映了相互作用细胞的结合亲和力。(2)利用功能阻断单克隆抗体和高度特异性的酶阐明pmn -肿瘤细胞粘附相互作用的基本分子和信号机制；(3)在剪切流动中跟踪单个pmn，并利用灌注室与表观荧光视频显微镜系统描述其与表面固定肿瘤细胞相互作用的动力学和模式。对于该提案的教育部分，PI的目标是在本科和研究生阶段开发一个创新的大学范围内的蜂窝工程课程。这一目标将通过开发一套有凝聚力的讲座课程和建立一个顶点实验课程来实现，通过接触生物工程研究中使用的各种实验工具和技术，学生将获得宝贵的实践经验。为了促进高中学生接触生物工程，将同时制定一项外展计划。该策略包括提高地区高中教师的教育水平，并开发一个基于互联网的模块，使用动画和音频/视频剪辑来介绍细胞工程的选定主题，以努力将这些材料作为高级科学课程的一部分。

PI's objectives are to: (1) Investigate the kinetics of PMN-tumor cell aggregate formation as a function of shear rate, and states of PMN/tumor cell activation. These data will be analyzed using a mathematical model based on Smoluchowski's two-body collision theory that will provide numerical estimates of an important cellular property termed adhesion efficiency, which reflects the binding affinity of interacting cells. (2) Elucidate the fundamental molecular and signaling mechanisms of PMN-tumor cell adhesive interactions using function blocking monoclonal antibodies and highly specific enzymes will, (3) Track individual PMNs in shear flow and delineate the dynamics and pattern of their interactions with surface-anchored tumor cells using a perfusion chamber coupled with an epifluorescence videomicroscopy system.For the educational component of this proposal, the PI aims to develop an innovative university-wide curriculum in Cellular Engineering at both the undergraduate and graduate levels. This goal will be met through the development of a cohesive set of lecture courses and the establishment of a capstone laboratory course in which students will obtain valuable hands-on experience, by being exposed to a wide array of experimental tools and techniques used in bioengineering research. To promote exposure of Bioengineering to high-school students, an outreach program will be developed in parallel. The strategy involves the educational enrichment of regional high-school teachers and the development of an internet-based module using animation and audio/video clips on selected topics of Cellular Engineering in an effort to introduce this material as a section in an advanced science course.