Study of DNA-binding Proteins Using a Mechanical Nanodevice

该项目将开发一种基于纳米设备的方法，在单分子基础上研究蛋白质与DNA的相互作用。具体地说，该纳米设备将通过检测探针DNA中诱导的构象变化来监测单个蛋白质结合事件。这代表了一种新的分子检测范式，即通过单分子探针中诱导的构象变化来检测目标分子。分子尺度的设备有望给科学技术带来革命性的变化，而展示一种实用的单分子蛋白质检测设备将是该领域发展的重要一步。从科学上讲，深入了解分子识别和机械变形之间的相互作用将影响我们对生物聚合物中变构控制机制的理解。研究生和博士后研究员将接受最先进的光学和微机械技术来操纵单分子的培训。这项研究跨越多个学科，因此提供了一个极好的机会，拓宽研究生和博士后研究人员对分子生物物理学和纳米技术当前进展的科学视野。生命的分子--蛋白质、DNA--在活细胞内以壮观的分子舞蹈相互作用，伴侣必须找到对方并指导对方的脚步。传统的分析方法，如X射线结晶学，通过时间冻结的快照来检查这些过程。这里提出的研究将开发一种新的方法，当分子舞蹈发生时，直接观察它们的某些步骤。具体地说，该项目将使用纳米设备来观察单个蛋白质分子与一小段DNA相互作用的过程。该项目的成功成果将在科学上加深我们对生物系统中分子识别如何与分子变形相耦合的知识；在技术上，它将展示一个基于纳米技术的高灵敏度蛋白质检测平台。研究生和博士后研究员将接受最先进的光学和微机械技术来操纵单分子的培训。这项研究跨越多个学科，从而为研究生和博士后研究人员提供了一个最好的机会，拓宽他们对分子生物物理学和纳米技术当前进展的科学看法。

This project will develop a nano-device based method to study protein-DNA interactions on a single molecule basis. Specifically, the nano-device will monitor single protein binding events by detecting the conformational change induced in the probe DNA. This represents a new paradigm of molecular detection, whereby the target molecule is detected through the conformational change induced in a single-molecule probe. Molecular scale devices hold the promise to revolutionize science and technology, and demonstrating a practical single molecule device for protein detection will be a significant step in the development of the field. Scientifically, gaining insight into the interplay between molecular recognition and mechanical deformation will impact our understanding of allosteric control mechanisms in bio-polymers. Graduate students and postdoctoral fellows will be trained in state-of-the-art optical and micro-mechanical techniques to manipulate single molecules. This research cuts across disciplines and thus offers an excellent opportunity to broaden the scientific outlook of graduate students and postdoctoral researchers on current advances in molecular biophysics and nano-technology. The molecules of life - proteins, DNA - interact within the living cell in a spectacular molecular dance, where partners must find each other and direct each other's steps. Traditional methods of analysis such as X-ray crystallography examine these processes through snapshots frozen in time. The research proposed here will develop a new method to directly observe certain steps of the molecular dance as they happen in real time. Specifically, the project will employ a nano-device to observe the process of a single protein molecule interacting with a short stretch of DNA. The successful outcome of the project will, scientifically, build up our knowledge of how molecular recognition is coupled to molecular deformation in biological systems; technologically, it will demonstrate a nano-technology based platform for high-sensitivity protein detection. Graduate students and postdoctoral fellows will be trained in state-of-the-art optical and micro-mechanical techniques to manipulate single molecules. This research cuts across disciplines and thus offers an optimal opportunity to broaden the scientific outlook of graduate students and postdoctoral researchers on current advances in molecular biophysics and nano-technology.