Physical and Biochemical Characterization of the Portal Complex of Bacteriophage Lambda

DNA包装是许多双链DNA病毒组装的关键步骤，包括痘病毒、疱疹病毒和许多噬菌体。在所有情况下，病毒基因组通过末端酶插入到预先形成的衣壳中。DNA通过门户进入衣壳，门户是所有这些病毒衣壳中发现的甜甜圈状结构。这个实验室的长期目标是详细了解病毒基因组包装的过程。本项目研究了噬菌体λ中的DNA包装作为模型系统，以了解病毒组装的基本机制。在病毒衣壳成熟过程中，λ门户被广泛修饰，本项目的主要目标是表征λ门户的化学和结构修饰，并定义每个修饰的生物学作用。此外，将鉴定和表征负责衣壳成熟的病毒蛋白酶。最近出现的“新的”病毒包装系统，在纳米科学和工程的病毒包装系统的潜力，以及生物武器的威胁越来越大，强调需要了解病毒的发展在最基本的水平。这项研究的结果将有助于这一重要的知识基础，并使人们能够对新的和正在出现的生物威胁作出迅速反应。更广泛的影响：博士前和博士后学生，包括在科学领域代表性不足的少数群体成员，将参与这项工作。因此，该项目将有助于培养一批不同的未来科学家。

DNA packaging is a critical step in the assembly of many double-stranded DNA viruses, including poxvirus, the herpesviruses, and many bacteriophages. In all cases, the viral genome is inserted into a pre-formed capsid by a terminase enzyme. DNA passes into the capsid through the portal, a doughnut-shaped structure found in the capsids of all of these viruses. The long-range goal of this lab is to understand, in detail, the process of viral genome packaging. The present project examines DNA packaging in bacteriophage lambda as a model system to understand the basic mechanisms of virus assembly. The lambda portal is extensively modified during the maturation of the viral capsid, and a major goal of this project is to characterize the chemical and structural modifications of the lambda portal, and to define the biological role of each modification. In addition, the viral protease responsible for capsid maturation will be identified and characterized. The recent emergence of "new" viral scourges, the potential of viral packaging systems in nanosciences and engineering, and the increasing threat of biological weapons underscore the need to understand virus development at the most fundamental level. The results of this research will contribute to this critical knowledge base, and make possible a rapid response to new and emerging biological threats. Broader Impacts: Pre-doctoral and post-doctoral students, including members of minority groups that have been underrepresented in science, will participate in this work. The project will thus serve to train a diverse group of future scientists.