Chemical Methods to Control RNA Interference with Light

通过这一奖项，生命过程化学计划支持堪萨斯城密苏里大学的西蒙·弗里德曼教授开发和改进光激活RNA干扰(LARI)方法的研究，这是一种正在开发的用光控制基因表达的技术。具体地说，利用这一工具，弗里德曼团队的目标是通过RNA干扰对基因敲除进行空间和时间控制，并控制这种敲除的程度。为了改进这一方法，将开发新的不耐光基团并将其连接到小RNA(siRNA和dsRNA)的末端，并在模型系统中评估它们用光减少基因表达的能力。这将包括对转基因和内源性基因靶标中基因表达的光依赖敲除。这种改进的方法将用于检查和解决一系列生物系统中的问题，包括与发育生物学和组织工程相关的问题。除了对学生进行化学和生物方面的培训外，拟议工作的更广泛影响针对的是受LARI影响的直接科学界以外的社区。在两个项目中的第一个项目中，PI将完善一系列演示，先前开发的演示通过展示如何应用于非实验室情况来帮助学生理解化学原理的普遍性。在第二项拟议的活动中，国际和平协会将为当地社区组织一系列关于科学的讨论。这些电影将以描述著名科学家生活的传记科学电影为中心。PI将以这些电影为起点，讨论正在调查的具体科学，以及科学研究的性质，以及如何提出和最终解决科学问题。

With this award, the Chemistry of Life Processes program is supporting the research of Professor Simon Friedman at the University of Missouri at Kansas City to develop and refine the method of Light Activated RNA Interference (LARI), a technique being developed to control gene expression with light. Specifically, with this tool, the Friedman group aims to exert spatial and temporal control of gene knockdown via RNA-interference, and also to control the extent of this knockdown. To refine the approach, new photolabile groups will be developed and attached to the termini of small RNAs (siRNA and dsRNA), and their ability to reduce gene expression with light will be assessed in model systems. This will include the light dependent knockdown of gene expression in transfected and endogenous gene targets. The refined method will be used to examine and address questions in a range of biological systems, including those related to developmental biology and tissue engineering. In addition to the training of students at the interface of chemistry and biology, the Broader Impacts of the proposed work are aimed at the community beyond the immediate scientific community affected by LARI. In the first of two projects, the PI will refine a series of demonstrations, previously developed to help students understand the universality of chemical principles by showing how they apply to non-laboratory situations. In a second proposed activity, the PI will organize a series of discussions about science for the local community. These will be centered on biographical science movies that described the life of famous scientists. The PI will use these films as a starting point to discuss the specific science that was being investigated, and also the nature of scientific inquiry, and how scientific questions are posed and ultimately addressed.