SENSORS: Integrated Molecular Sensors Derived from Combinatorial Protein and DNA Libraries

实验和集成活动传感器：来自组合蛋白质和DNA文库的集成分子传感器Bruce A Armitage（EIA - 0330135）摘要本研究是关于来自蛋白质和DNA组合文库的集成分子传感器的构建。集成的分子传感器至少由两个组件组成：与目标分子（分析物）结合的识别元件，以及将结合事件转换为可读信号的信号转换器。识别元件将从上述组合文库衍生。这些文库将通过蛋白质的遗传工程或DNA的化学合成来产生。假设至少一些文库成员将折叠成与靶的某个部分互补的三维结构。然后，将使用受控的体外选择程序来分离文库中以高亲和力结合特定靶标（即蓖麻毒素A链蛋白）的成员。这项研究的广泛影响是多重的。 虽然提出的大部分工作是一个基本的性质，在选择中使用的目标分子，蓖麻毒素A链蛋白是直接相关的。这一目标很重要，因为最近人们对在生物恐怖主义和生物战中使用蓖麻毒素（包括A链）的关切加剧。 此外，为构建集成分子传感器而开发的方法可以应用于许多其他目标。通过本研究可以实现临床和现场使用的功能传感器。从事该项目的学生将接触到广泛的技术，包括化学合成，分子生物学和光谱学。除了预期的学年努力，研究生导师和本科生将被招募为一个特殊的夏季研究团队，将花十周的时间在一个高度协作，多学科的环境中工作。

EXPERIMENTAL AND INTEGRATED ACTIVITIES SENSORS: Integrated Molecular Sensors Derived from Combinatorial protein and DNA LibrariesBruce A Armitage(EIA - 0330135)AbstractThis research is on the construction of integrated molecular sensors derived from combinatorial libraries of proteins and DNA. An integrated molecular sensor consists minimally of two components: the recognition element that binds to the target molecule (analyte), and the signal transducer that converts the binding event into a readable signal. The recognition element will be derived from the aforementioned combinatorial libraries. These libraries will be generated either through genetic engineering for proteins or through chemical synthesis for DNA. The assumption is that at least some of the library members will fold into a three-dimensional structure that is complementary to some part of the target. Controlled in vitro selection procedures will then be used to isolate members of the libraries that bind to a particular target, namely the ricin A-chain protein, with high affinity. The broader impacts of this research are several-fold. While much of the work proposed is of a fundamental nature, the target molecule to be used in the selections, the ricin A-chain protein is of immediate relevance. This target is important due to recently heightened concerns about the use of the ricin toxin, which includes the A-chain, in bioterrorism and biowarfare. Moreover, the methods to be developed for constructing integrated molecular sensors can be applied to many other targets. Functional sensors for use in the clinic and the field can be realized from this research. Students working on this project will be exposed to a broad range of techniques including chemical synthesis, molecular biology and optical spectroscopy. In addition to the expected academic year efforts, graduate student mentors and undergraduate students will be recruited for a special summer research team that will spend ten weeks working in a highly collaborative, multidisciplinary environment.