Collaborative Research: DNA Packing of Bacteriophages: Liquid Crystal Modeling through Analysis, Knot Theory and Numerical Simulation.

合作研究：噬菌体的 DNA 包装：通过分析、结理论和数值模拟进行液晶建模。

• 批准号: 1817156
• 负责人: Mariel Vazquez
• 金额: $ 48万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1817156&HistoricalAwards=false
• 关键词: Collaborative; Research; DNA; Packing; Bacteriophages

Bacteriophages are viruses that infect bacteria and whose genome is, in some cases, a double stranded DNA molecule. In order to develop strains of double stranded (ds) DNA bacteriophages that can be efficiently used in nanotechnology and for treatment of bacterial infections, a detailed mathematical and biophysical characterization of the packing and delivery of the viral genome is required. Paradoxically, very little is known about these processes due to the extreme density and pressure conditions that the DNA is subject to inside the virus. In the proposed research, the investigators will combine experimental work and the theory of liquid crystals to determine the properties and organization of the DNA molecule inside bacteriophages and of its release. The project will establish a firm theoretical framework for genome delivery in nano-technological applications. In particular, it will produce the first analytical model describing the liquid crystalline phase of DNA in confinement. Two postdoctoral fellows and at least two graduate students will be trained each year. Results and materials will be broadly disseminated, through open access as well as standard journals and conference presentations. Materials developed in this project will be presented at the UC Davis program for high school students COSMOS. Collaborations and contacts with device development laboratories will be established.The overarching hypothesis of the project is that the DNA molecule inside the viral capsid forms a hexagonal chromonic liquid crystal phase for which mathematical models are lacking. In the proposed project, the investigators will first build a mechanical model determined by an energy function that incorporates information from cryo-EM data, information from semiflexible polymers, results from Onsager theory of lyotropic liquid crystals and parameters from experiments on chromonic liquid crystals. Next, they will extend their mechanical model by including polyelectrolyte gel features, acknowledging the presence of water with many types of ions and their interaction with the negative charge of the DNA molecule. Third, the investigators will develop models of delivery of genomes with different biophysical properties. Furthermore, the investigators hypothesize that defects in the DNA liquid crystalline ordering are manifested as knots and DNA kinks. The proposed mathematical and computational models will be, both, guided and validated by multiple experimental techniques including cryo-EM, topological analysis, estimation of osmotic pressures and delivery of DNA sequences. The ultimate goal of this project is to construct and analyze a mathematical model of chromonic liquid crystals capable of making packing, pressure and delivery predictions.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.

噬菌体是感染细菌的病毒，其基因组在某些情况下是双链DNA分子。为了开发可有效用于纳米技术和治疗细菌感染的双链（ds）DNA噬菌体菌株，需要病毒基因组的包装和递送的详细数学和生物物理表征。奇怪的是，由于DNA在病毒内部所处的极端密度和压力条件，人们对这些过程知之甚少。在拟议的研究中，研究人员将联合收割机实验工作和液晶理论相结合，以确定噬菌体内DNA分子的性质和组织及其释放。该项目将为纳米技术应用中的基因组传递建立一个坚实的理论框架。特别是，它将产生第一个分析模型，描述限制DNA的液晶相。每年将培养两名博士后研究员和至少两名研究生。成果和材料将通过开放获取以及标准期刊和会议演示文稿广泛传播。在这个项目中开发的材料将在加州大学戴维斯分校的高中生COSMOS计划。该项目的首要假设是，病毒衣壳内的DNA分子形成了一种六边形的有色液晶相，但缺乏数学模型。在拟议的项目中，研究人员将首先建立一个由能量函数确定的力学模型，该能量函数包含来自cryo-EM数据的信息，来自半柔性聚合物的信息，来自溶致液晶Onsager理论的结果和来自有色液晶实验的参数。接下来，他们将通过包括凝胶特征来扩展他们的力学模型，承认水与许多类型的离子的存在以及它们与DNA分子的负电荷的相互作用。第三，研究人员将开发具有不同生物物理特性的基因组传递模型。此外，研究人员假设DNA液晶有序中的缺陷表现为结和DNA扭结。提出的数学和计算模型将通过多种实验技术（包括冷冻EM、拓扑分析、渗透压估计和DNA序列递送）进行指导和验证。该项目的最终目标是构建和分析能够进行包装，压力和交付预测的有色液晶的数学模型。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Helical organization of DNA-like liquid crystal filaments in cylindrical viral capsids

• DOI: 10.1098/rspa.2022.0047
• 发表时间: 2022-10
• 期刊: Proceedings of the Royal Society A
• 作者: Pei-Yuan Liu;J. Arsuaga;M. Calderer;D. Golovaty;M. Vázquez;Shawn Walker

Chromonic liquid crystals and packing configurations of bacteriophage viruses

• DOI: 10.1098/rsta.2020.0111
• 发表时间: 2021-07-12
• 期刊: PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES
• 影响因子: 5
• 作者: Hiltner, Lindsey;Calderer, M. Carme;Vazquez, Mariel
• 通讯作者: Vazquez, Mariel

Quantitative Study of the Chiral Organization of the Phage Genome Induced by the Packaging Motor

• DOI: 10.1016/j.bpj.2020.03.030
• 发表时间: 2020-05-05
• 期刊: BIOPHYSICAL JOURNAL
• 影响因子: 3.4
• 作者: Cruz, Brian;Zhu, Zihao;Vazquez, Mariel
• 通讯作者: Vazquez, Mariel

Estimating properties of kinetoplast DNA by fragmentation reactions

• DOI: 10.1088/1751-8121/aaf15f
• 发表时间: 2018-12
• 期刊: Journal of Physics A: Mathematical and Theoretical
• 作者: L. Ibrahim;P. Liu;M. Klingbeil;Y. Diao;J. Arsuaga

Recent advances on the non-coherent band surgery model for site-specific recombination

• DOI: 10.1090/conm/746/15004
• 发表时间: 2018-10
• 期刊: Topology and Geometry of Biopolymers
• 作者: Allison H. Moore;M. Vázquez