RIG: Genetic and Molecular Basis of Bacteriophage Life History Variation

为了构建生物体，DNA被翻译成蛋白质，这些蛋白质组装成或指导物理结构的组装。对于大多数生物来说，这个过程几乎是难以想象的复杂，但其中最简单的细菌病毒(即噬菌体)又如何呢？例如，噬菌体lambda由一条被蛋白质壳包裹的DNA链组成。λ噬菌体的组装是如何控制的？控制机制中的随机性如何影响最终产品？进化是如何塑造控制机制的？这项研究的最终目标是确定噬菌体组装是如何控制的，评估变异在组装网络中的作用，并了解进化是如何塑造这个生物系统的。该项目是朝着这一目标迈出的第一步，因为它使用突变来系统地改变噬菌体结构蛋白的表达。有机体的反应将通过量化噬菌体繁殖产量的平均值和变异来评估。进化实验将进一步确定噬菌体如何应对噬菌体繁殖产量的变化。成功的完成将提供更清晰的图景，了解复杂的过程如何对系统范围的扰动做出反应，以及进化如何能够使过程返回最佳状态。拟议研究的更广泛影响包括鼓励残疾人参与科学研究，增加代表不足的少数群体对科学的参与，以及利用下一代科学仪器和最近开发的分子技术加强进化生物学的研究。该项目不仅将增加听障人士PI的机会，还将提高残疾科学家的能见度，并鼓励其他残疾人以探索科学为职业。作为代表不足的少数群体，PI敏锐地意识到在科学界促进包容性的重要性。国际和平协会积极努力提高科学素养，包括开设博客，向公众发表科学演讲，并参与一个网络百科全书项目。

To construct an organism, DNA is translated into proteins which are assembled into or direct the assembly of a physical structure. This process is almost unimaginably complex for most organisms, but what about the simplest of them, the bacterial viruses (i.e. phages)? For example, the coliphage lambda consists of a strand of DNA enclosed by a protein shell. How is the assembly of lambda phage controlled? How does stochasticity in the control mechanisms affect the ultimate product? How does evolution shape the control mechanisms? The ultimate goal of this research is to determine how phage assembly is controlled, to assess the role of variation in the assembly network, and to understand how evolution shapes this biological system. This project is an initial step towards that goal as it uses mutagenesis to systematically alter the expression of phage structural proteins. Organismal responses will be assessed by quantifying mean and variation of phage reproductive output. Evolution experiments will further determine how phages respond to changes in phage reproductive output. Successful completion will provide a clearer picture of how a complex process responds to system-wide perturbation, and how evolution is able to return the process to an optimal state. The broader impacts of the proposed research include encouraging persons of disability to participate in scientific research, increasing the participation of underrepresented minorities in science and enhancing research in evolutionary biology with next-generation scientific instrumentation and recently developed molecular techniques. The project will not only improve opportunities for the PI, a hearing impaired individual, but will increase the visibility of disabled scientists and encourage other disabled individuals to explore science as a career. As an underrepresented minority, the PI is keenly aware of the importance of fostering inclusiveness in the scientific community. The PI is active in efforts to increase scientific literacy including keeping a blog, giving science talks to the general public and participating in a web encyclopedia project.