Study of DNA-binding Proteins Using a Mechanical Nanodevice

使用机械纳米装置研究 DNA 结合蛋白

• 批准号: 0405632
• 负责人: Giovanni Zocchi
• 金额: $ 30万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0405632&HistoricalAwards=false
• 关键词: Study; DNA; binding; Proteins; Using

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.

该项目将开发一种基于纳米设备的方法，以单个分子研究蛋白-DNA相互作用。具体而言，纳米设备将通过检测探针DNA中诱导的构象变化来监测单蛋白结合事件。这代表了分子检测的新范式，从而通过单分子探针中诱导的构象变化检测靶分子。分子尺度设备有望彻底改变科学和技术，并且证明用于蛋白质检测的实用单分子设备将是该领域发展的重要一步。从科学上讲，洞悉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以最先进的光学和微型力学技术来操纵单分子的培训。这项研究跨越了学科，因此提供了一个绝佳的机会，可以扩大研究生和博士后研究人员在分子生物物理学和纳米技术方面的进步的科学前景。生命的分子 - 蛋白质，DNA-在壮观的分子舞中在活细胞中相互作用，伴侣必须互相找到彼此并指导彼此的步骤。传统的分析方法，例如X射线晶体学，通过及时冻结的快照检查这些过程。这里提出的研究将开发一种新方法，以直接观察分子舞的某些步骤，因为它们是实时发生的。具体而言，该项目将采用纳米依赖性来观察单个蛋白质分子与短暂的DNA相互作用的过程。从科学上讲，该项目的成功结果将建立我们对分子识别如何与生物系统中的分子变形结合在一起的知识。从技术上讲，它将展示一个基于纳米技术的高敏蛋白检测平台。研究生和博士后研究员将接受以最先进的光学和微型力学技术来操纵单分子的培训。这项研究跨越了学科，因此提供了最佳机会，以扩大研究生和博士后研究人员在分子生物物理学和纳米技术方面的进步的科学前景。