CAREER: Integrated Scanning and Optical Imaging Techniques to Enable Understanding of Live Cell Dynamics - From Molecular Biology to Physiological Function

在这份CAREER提案中，PI建议开发一种独特的集成显微镜技术，该技术广泛适用于活细胞的分子动力学研究。该技术的能力将通过研究活细胞适应其局部机械环境的动态结构-功能关系来证明。该研究和教育计划的目标是：(1)开发和演示一种最先进的集成显微镜系统，该系统将原子力显微镜（AFM）、快速旋转盘（FSD）共聚焦显微镜和全内反射荧光（TIRF）结合到一个仪器中；(2)应用集成afm -光学成像技术研究细胞在机械力作用下重组基本过程中的蛋白质动力学；(3)实施一项教育计划，该计划将：(a)使高中生，特别是女孩和代表性不足的少数民族，接触到生物物理科学方面的进展，以提高他们从事科学事业的兴趣；(b)开发创新的研究生课程模块，使用互动和视觉技术帮助生命科学和工程专业的学生更好地理解先进成像的物理学；(c)建立一个有关原子力显微镜理论及其生物学应用的网站，作为一个开放源码的互动教学工具。教育计划以女生和少数民族学生为中心，通过“星期六上午生物物理学：想象生活”的新课程，向高中学生介绍这一跨学科研究领域的基本科学概念和实践经验。PI还将指导一名研究生和两名本科生进行这个跨学科的前沿研究项目。

In this CAREER proposal the PI proposes to develop a uniquely integrated microscopy technology that is broadly applicable across a wide range of molecular dynamic studies in live cells. The technique's capabilities will be demonstrated by studying the dynamic structure-function relationship of the living cell as it adapts to its local mechanical environment. The objectives of the proposed research and educational plan are to: (1) Develop and demonstrate a state-of-the-art integrated microscope system that combines Atomic Force Microscopy (AFM), Fast Spinning-Disk (FSD) Confocal Microscopy and Total Internal Reflection Fluorescence (TIRF) into one instrument; (2) Apply the integrated AFM-optical imaging technology to study protein dynamics in the fundamental process of cellular reorganization in response to mechanical force; (3) Implement an educational plan that will: (a) expose high school students, especially girls and underrepresented minorities, to advancements in the biophysical sciences with the aim of enhancing their interest in pursuing careers in science; (b) develop an innovative graduate course module that uses interactive and visual techniques to help life science and engineering students better understand the physics of advanced imaging; and (c) develop a website on AFM theory and its biological applications to serve as an open-source interactive teaching tool. The education plan will introduce basic science concepts of this interdisciplinary field of research and hands on experience to high school students, focusing on girls and minority students, through a new program: Saturday Morning Biophysics: Image Life! The PI will also mentor one graduate and two undergraduate students in this interdisciplinary, cutting-edge research project.