CAREER: Advanced Single Molecule Techniques on DNA-Protein Interactions

该项目的科学组成部分侧重于开发和利用先进的单分子技术来研究dna -蛋白质相互作用的基础。x射线晶体学和核磁共振等方法为生物分子提供了大量的结构细节，但在很大程度上仅限于基于集合测量的静态视图。在这项工作中，单分子荧光检测和光谱学将与纳米机械操作、生物友好表面工程和定点诱变相结合，构建合适的DNA结构和工程蛋白，并在单分子水平上研究它们的动态相互作用。该项目的教育部分侧重于通过开设一门课程，向物理、化学、生物工程和生物学专业的学生介绍生物物理学的传统和现代技术，从而扩大该大学的物理学本科课程。该课程将有一个强大的实验室组成部分，将与大学的REU计划和一个新的部门高级论文计划相结合。学生将学习到一些最新的生物物理技术，包括贴片拍、原子力显微镜、光学镊子、磁镊子、单分子荧光检测和光谱学。该项目由数学和物理科学理事会物理司和多学科活动办公室以及生物科学理事会分子和细胞生物科学司共同资助。

The scientific component of this project focuses on the development and utilization of advanced single-molecule techniques to study the fundamentals of DNA-protein interactions. Methods such as x-ray crystallography and nuclear magnetic resonance have provided a vast array of structural detail for biological molecules, yet are largely limited to a static view that is based on ensemble measurements. In this work single molecule fluorescence detection and spectroscopy will be combined with nano-mechanical manipulations, bio-friendly surface engineering, and site-directed mutagenesis to construct suitable DNA structures and engineered proteins and to study their dynamic interactions at the single molecule level. The educational component of the project focuses on the expansion of the physics undergraduate program at the university through a course that will introduce students in physics, chemistry, bioengineering, and biology to both traditional and modern techniques in biophysics. The course will have a strong laboratory component that will be integrated with the university's REU program and a new departmental senior thesis program. Students will be introduced to some of the latest biophysical techniques, including patch clap, atomic force microscopy, optical tweezers, magnetic tweezers, and single molecule fluorescence detection and spectroscopy. This project is jointly funded by the Division of Physics and the Office of Multidisciplinary Activities in the Directorate for Mathematical and Physical Sciences and by the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.