Biochemical, Biophysical and Structural Characterization of Phage Lambda Capsid Assembly and Maturation

噬菌体 Lambda 衣壳组装和成熟的生化、生物物理和结构表征

• 批准号: 2016019
• 负责人: Carlos Catalano
• 金额: $ 90万
• 依托单位: University of Colorado at Denver
• 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: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2016019&HistoricalAwards=false
• 关键词: Biochemical; Biophysical; Structural; Characterization; Phage

The herpesviruses and many bacteriophages, viruses that infect bacteria, share similar developmental pathways. An essential step for all of them is the assembly of a capsid shell that protects the viral genome in the environment. The capsid self-assembles from multiple copies of a major capsid protein and a scaffolding “chaperone” protein. The interactions required for assembly and subsequent stability of the shell are of fundamental importance to virus replication. This project studies and defines these interactions which will advance our understanding of how the viruses replicate and maintain infectivity in the environment. An understanding of these forces is also necessary for the rational development of anti-viral therapeutics and to adapt the structures for novel nanomaterials for scientific and potentially health-related applications. The work performed in this project will be conducted by promising young scientific investigators from undergraduate to graduate to post-doctoral fellows and will serve to train the next generation of scientists in the American work force.Specifically, the project will define the structural and thermodynamic interactions between the capsid proteins required for shell assembly and stability. The studies will employ biochemical (mutagenesis), biophysical (analytical ultracentrifugation), computational (molecular dynamics) and structural (Nuclear Magnetic Resonance, crystallography, cryo-Electron Microscopy) approaches in a coordinated manner. Fundamental interactions between the scaffolding and capsid proteins required for high-fidelity shell assembly are also interrogated. The results of the studies will reveal molecular interactions essential to shell assembly and stability in the large double-stranded DNA viruses, both prokaryotic and eukaryotic. These data have significant implications in anti-viral therapeutics, phage therapy and nanotechnology applications.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.

疱疹病毒和许多噬菌体（感染细菌的病毒）有着相似的发育途径。它们的一个重要步骤是组装衣壳，在环境中保护病毒基因组。衣壳由一个主要衣壳蛋白和一个支架“伴侣”蛋白的多个拷贝自组装而成。组装所需的相互作用和壳的后续稳定性对病毒复制至关重要。该项目研究并定义了这些相互作用，这将促进我们对病毒如何在环境中复制和保持传染性的理解。了解这些作用力对于合理开发抗病毒疗法和调整新型纳米材料的结构以用于科学和潜在的健康相关应用也是必要的。本项目的工作将由有前途的年轻科研人员进行，从本科生到研究生再到博士后，并将用于培养美国劳动力中的下一代科学家。具体来说，该项目将定义壳组装和稳定性所需的衣壳蛋白之间的结构和热力学相互作用。这些研究将采用生物化学（诱变）、生物物理（分析超离心）、计算（分子动力学）和结构（核磁共振、晶体学、冷冻电子显微镜）等方法进行协调。高保真壳组装所需的支架和衣壳蛋白之间的基本相互作用也被询问。研究结果将揭示分子相互作用对原核和真核大双链DNA病毒的壳组装和稳定性至关重要。这些数据在抗病毒治疗、噬菌体治疗和纳米技术应用方面具有重要意义。该奖项反映了美国国家科学基金会的法定使命，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。