Collaborative Research: Physical parameters controlling viral DNA packaging and ejection

合作研究:控制病毒 DNA 包装和排出的物理参数

基本信息

  • 批准号:
    1716219
  • 负责人:
  • 金额:
    $ 60万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-08-01 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

Viruses are small infectious agents that only replicate inside the living cells of other organisms and can infect all types of life forms. This research will improve the understanding of key steps in the life-cycle of many viruses, the packaging of the DNA during viral assembly and the ejection of the DNA during infection of a host cell, as well as how these processes depend on the physical behavior of the tightly packed DNA. The project will not only shed light on the fundamental biology of viruses, but also on the physics of tightly confined DNA and the regulation of biological molecular motors which transport DNA. Graduate and undergraduate students will receive interdisciplinary training in the application of physics techniques to biology research and new experimental laboratory course materials will also be developed. K-12 outreach activities will be conducted and grade-school educational materials, including science books, kits, and games, will be evaluated for quality and scientific accuracy to provide online recommendations to schools and museums.Recent studies have shown that the kinetics of the packaging of double stranded DNA in bacterial viruses is dominated by the dynamics and energetics of the tightly packed DNA. In the biological regime to be studied, with repulsive DNA-self interactions, the DNA relaxes only very slowly towards an equilibrium conformation. Large forces build that resist DNA confinement and later help drive ejection during infection of a host cell. Bacteriophage phi29 will be studied as a model system and the packaging of single DNA molecules will be directly measured with optical tweezers. The dependence of packaging kinetics on initial motor velocity, dependent on ATP concentration, will be studied. Lower initial velocity is hypothesized to reduce formation of highly unfavorable DNA conformations, yielding decreased heterogeneity in the dynamics, lower relative slowing during filling, and less motor pausing, slipping, and stalling. A hypothesis to be tested is that allosteric regulation of the portal motor helps packaging complete as fast as possible by throttling down the motor velocity to mitigate formation of unfavorable DNA conformations. How packaging kinetics, force, and DNA relaxation depend on temperature and ionic conditions will also be studied. Motor velocity increases significantly with temperature, and motor slowing during filling depends on ionic screening conditions. Whereas faster initial velocity may cause greater relative slowing during filling, increased temperature or ionic screening may accelerate DNA relaxation. How packaging conditions and aging affect DNA ejection and viral infectivity will also be studied. Conditions affecting the DNA conformation during packaging, and aging, may impact DNA ejection. Conditions that increase forces resisting packaging or decrease DNA relaxation time may enhance ejection. The biological impact of these parameters will be investigated by examining their effects on virus infectivity.
病毒是一种小型的感染因子,只能在其他生物体的活细胞内复制,并且可以感染所有类型的生命形式。这项研究将提高对许多病毒生命周期的关键步骤的理解,病毒组装期间DNA的包装和宿主细胞感染期间DNA的喷射,以及这些过程如何依赖于紧密包装的DNA的物理行为。该项目不仅将揭示病毒的基本生物学,而且还将揭示紧密受限DNA的物理学和运输DNA的生物分子马达的调节。研究生和本科生将接受跨学科的物理技术应用于生物学研究的培训,并将开发新的实验实验课程材料。将开展K-12教育外展活动,对科学书籍、教材、游戏等小学教育教材的质量和科学准确性进行评价,并向学校和博物馆提供在线推荐。最近的研究表明,细菌病毒双链DNA的包装动力学主要是由紧密包装DNA的动力学和能量学决定的。在待研究的生物体系中,由于DNA与自身相互作用的排斥性,DNA只能非常缓慢地向平衡构象放松。巨大的力量形成抵抗DNA限制,随后在宿主细胞感染期间帮助驱动喷射。噬菌体phi29将作为一个模型系统进行研究,单个DNA分子的包装将用光学镊子直接测量。包装动力学的依赖于初始电机速度,依赖于ATP浓度,将进行研究。假设较低的初始速度可以减少高度不利的DNA构象的形成,减少动力学的异质性,降低填充过程中的相对慢速,减少电机暂停,打滑和失速。一个有待检验的假设是,门脉马达的变构调节通过降低马达速度来减轻不利DNA构象的形成,从而帮助包装尽可能快地完成。如何包装动力学,力,和DNA弛豫取决于温度和离子条件也将进行研究。随着温度的升高,电机速度显著增加,填充过程中的电机减速取决于离子筛选条件。虽然更快的初始速度可能会导致填充过程中更大的相对减速,但温度升高或离子筛选可能会加速DNA松弛。包装条件和老化如何影响DNA喷射和病毒感染性也将被研究。在包装和老化过程中影响DNA构象的条件可能会影响DNA的排出。增加抗包装力或减少DNA松弛时间的条件可能会增强喷射。将通过检查这些参数对病毒传染性的影响来研究它们的生物学影响。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Role of DNA-DNA sliding friction and nonequilibrium dynamics in viral genome ejection and packaging.
  • DOI:
    10.1093/nar/gkad582
  • 发表时间:
    2023-08-25
  • 期刊:
  • 影响因子:
    14.9
  • 作者:
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Douglas Smith其他文献

A Study of Healthcare Services Received under Alternative Medicare Insurance Plans
根据替代医疗保险计划获得的医疗服务研究
Insulin, Glucose, Amino Acid, and Lipid Metabolism in Chronic Renal Insufficiency
慢性肾功能不全中的胰岛素、葡萄糖、氨基酸和脂质代谢
  • DOI:
  • 发表时间:
    1984
  • 期刊:
  • 影响因子:
    0
  • 作者:
    R. DeFronzo;A. Alvestrand;Douglas Smith
  • 通讯作者:
    Douglas Smith
Stability of the assemblage iron-rich orthopyroxene-olivine-quartz
富铁斜方辉石-橄榄石-石英组合的稳定性
  • DOI:
    10.2475/ajs.271.4.370
  • 发表时间:
    1971
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Douglas Smith
  • 通讯作者:
    Douglas Smith
Changes in water quality following tidal inundation of coastal lowland acid sulfate soil landscapes
沿海低地酸性硫酸盐土壤景观潮汐淹没后的水质变化
  • DOI:
  • 发表时间:
    2009
  • 期刊:
  • 影响因子:
    0
  • 作者:
    S. Johnston;R. Bush;L. Sullivan;E. Burton;Douglas Smith;M. Martens;A. McElnea;C. Ahern;B. Powell;Luisa P Stephens;Steven T Wilbraham;Simon van Heel
  • 通讯作者:
    Simon van Heel
Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus
受体原癌基因 fms 的病毒同源物在羧基末端的结构改变
  • DOI:
    10.1038/320277a0
  • 发表时间:
    1986-03-20
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Lisa Coussens;Charles Van Beveren;Douglas Smith;Ellson Chen;Richard L. Mitchell;Clare M. Isacke;Inder M. Verma;Axel Ullrich
  • 通讯作者:
    Axel Ullrich

Douglas Smith的其他文献

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{{ truncateString('Douglas Smith', 18)}}的其他基金

Collaborative Research: Controlling the Microstructure for Improved Mechanical Properties of Large-scale Polymer Composite Structures Made by Big Area Additive Manufacturing
合作研究:控制微观结构以改善大面积增材制造制成的大型聚合物复合结构的机械性能
  • 批准号:
    2055628
  • 财政年份:
    2021
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
RAPID/Collaborative Research: Multi-Platform 3-D Data Preservation of Tornado Damage to Engineered Structures in Texas during November 16-17, 2015
RAPID/协作研究:2015 年 11 月 16 日至 17 日期间德克萨斯州工程结构龙卷风损坏的多平台 3D 数据保存
  • 批准号:
    1623752
  • 财政年份:
    2016
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
NSF East Asia and Pacific Summer Institute (EAPSI) for FY 2013 in China
2013 财年 NSF 东亚及太平洋暑期学院 (EAPSI) 在中国
  • 批准号:
    1316974
  • 财政年份:
    2013
  • 资助金额:
    $ 60万
  • 项目类别:
    Fellowship Award
Collaborative Research: Mechanisms of Termination of Viral DNA Packaging
合作研究:病毒DNA包装终止机制
  • 批准号:
    1158328
  • 财政年份:
    2012
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
SBIR Phase I: Double Patterning using Optical Lithography for Fabricating 50 nm Nanostructures on Meter Scale Substrates
SBIR 第一阶段:使用光学光刻在米级基板上制造 50 nm 纳米结构的双重图案化
  • 批准号:
    0945432
  • 财政年份:
    2010
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
Investigating the Collisional and Dynamical Evolution of Comets
研究彗星的碰撞和动力学演化
  • 批准号:
    1010012
  • 财政年份:
    2010
  • 资助金额:
    $ 60万
  • 项目类别:
    Continuing Grant
Dynamics and Energetics of Viral DNA Packaging and Ejection
病毒 DNA 包装和喷射的动力学和能量学
  • 批准号:
    0848905
  • 财政年份:
    2009
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
Phenomenological-Based Constitutive Model and Simulation of Fiber Interaction for Short Fiber Composite Processing
基于现象学的短纤维复合材料加工纤维相互作用本构模型与仿真
  • 批准号:
    0727399
  • 财政年份:
    2007
  • 资助金额:
    $ 60万
  • 项目类别:
    Continuing Grant
SGER: Effective Theories of System Design
SGER:有效的系统设计理论
  • 批准号:
    0737840
  • 财政年份:
    2007
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
Incorporating Higher Order Tensors in the Computation of Polymer Composite Mechanical Properties
将高阶张量纳入聚合物复合材料力学性能的计算
  • 批准号:
    0522694
  • 财政年份:
    2005
  • 资助金额:
    $ 60万
  • 项目类别:
    Continuing Grant

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  • 批准号:
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