The Mechanics of Viral Genomes: Single-Molecule Studies

该奖项的研究目标是对病毒的基因组材料如何进入它们感染的细胞进行定量和机械性的理解。所有生命领域的细胞都会受到病毒的感染。这些病毒有多种不同的生活方式，通常涉及将它们的基因引入受感染宿主的不同方式。对于这些病毒中的一些，人们假设病毒内紧密包装的DNA产生的机械力产生了一个压力，将DNA注入宿主S体内。根据该奖项进行的研究将通过使用荧光显微镜观察单个病毒将其DNA注入单个细菌并测量喷射率来验证这一假设。通过使用不同的药物治疗，喷射过程的机制将被扰乱，从而提供了一幅驱动DNA易位的分子过程的图景。如果成功，这些研究将成为一个强有力的例子，说明支配病毒生活方式的物理过程与其生物功能之间的相互作用。此外，由于该方法将单分子实验与机械模型结合在一起，它将有助于解决关于病毒感染如何发生的长期争议。这项研究与一个以暑期课程为重点的教育计划紧密结合在一起。在暑期课程中，本科生、研究生和博士后来到获奖者S研究所进行为期两周的密集实验，将病毒喷射研究作为生物过程单分子研究的范式，生物过程是力学生物学的前沿之一。

The research objective of this award is to develop a quantitative and mechanistic understanding of how the genomic material of viruses enters the cells they are infecting. Cells across all domains of life are subjected to infection by viruses. These viruses have a multitude of different lifestyles which often involve different ways of introducing their genes into the infected host. For some of these viruses, it has been hypothesized that mechanical forces resulting from the tightly-packaged DNA within the virus creates a pressure which injects the DNA into the host?s interior. Studies conducted under this award will test this hypothesis by using fluorescence microscopy to watch individual viruses inject their DNA into individual bacteria and to measure the rate of ejection. By using different drug treatments, the mechanics of the ejection process will be perturbed providing a picture of the molecular processes that drive DNA translocation. If successful, these studies will serve as a powerful example of the interplay between the physical processes that govern the lifestyles of viruses and their biological functions. Further, since the approach merges single-molecule experiments with mechanical models, it will help settle a long standing controversy about how viral infections occur. The research is tightly integrated with an educational plan that focuses on summer time courses in which undergraduates, graduate students and postdocs come to the awardee?s institution for an intensive fortnight of experiments using the study of viral ejection as a paradigm for single-molecule studies of biological processes which represent one of the biological frontiers of mechanics.