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Hydrodynamics of confined DNA knots

受限 DNA 结的流体动力学

基本信息

批准号：
2016879
负责人：
Kevin Dorfman
金额：
$ 36.7万
依托单位：
University of Minnesota-Twin Cities
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2016879&HistoricalAwards=false
关键词：
Hydrodynamics confined DNA knots

项目摘要

Random thermal fluctuations can form knots in polymers such as DNA much like shaking headphones can cause knots in the cord. As a result, knots are common in long polymer chains. Knots also can be created by fluid flow. The objective of this project is to perform experiments that uncover how a knot is formed in a flow and how it is removed after formation. Broadly speaking, knotted polymers are important both to fundamental problems in biology and to applied topics in biotechnology. The immediate technological impacts of this problem lie in two emerging long-read genomics technologies: genome mapping and nanopore sequencing. Knotting in DNA also has a broader importance in biology, in particular for regulation of the genome.This project experimentally addresses two key scientific questions related to knotting of long polymers, using DNA as a model system. The first part focuses on how stalling DNA at a nanofluidic interface produces knots, focusing on developing mechanistic insights via fluorescence microscopy. The second part focuses on the transport properties of DNA knots. These experiments leverage nanochannels as a “hydrodynamic microscope” to isolate the hydrodynamic interactions within the knot from hydrodynamic interactions between the knot and the rest of the chain. Through this work, graduate students on the project will receive training in clean-room fabrication methods, fluorescence microscopy, image processing, and the theories of hydrodynamics and polymer physics. This project also involves a K-12 outreach project to develop science fair projects related to the research for high school students.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

随机的热波动可以在聚合物（如DNA）中形成结，就像摇动耳机可以在绳索中形成结一样。因此，结在长聚合物链中是常见的。结也可以由流体流动产生。该项目的目的是进行实验，揭示如何在流中形成结，以及如何在形成后去除结。广义地说，打结聚合物对生物学中的基本问题和生物技术中的应用课题都很重要。这个问题的直接技术影响在于两种新兴的长读基因组学技术：基因组作图和纳米孔测序。DNA中的打结在生物学中也具有更广泛的重要性，特别是对于基因组的调控。该项目以DNA为模型系统，通过实验解决了与长聚合物打结相关的两个关键科学问题。第一部分集中在如何失速DNA在纳米流体接口产生结，重点是通过荧光显微镜发展机制的见解。第二部分研究了DNA结的输运性质。这些实验利用纳米通道作为“流体动力学显微镜”，将结内的流体动力学相互作用与结和链的其余部分之间的流体动力学相互作用隔离。通过这项工作，该项目的研究生将接受洁净室制造方法，荧光显微镜，图像处理以及流体力学和聚合物物理理论的培训。该项目还涉及一个K-12推广项目，以开发与高中生研究相关的科学博览会项目。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。