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

实验和整合活性传感器：来源于组合蛋白质和DNA文库的整合分子传感器Bruce A Armitage(EIA-0330135)摘要本研究旨在构建来源于蛋白质和DNA组合文库的整合分子传感器。一个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中得到。这些文库将通过蛋白质的基因工程或DNA的化学合成来生成。假设至少有一些文库成员会折叠成一个三维结构，与目标的某一部分互补。然后，受控的体外选择程序将被用来分离与特定靶点结合的文库成员，即高亲和力的蓖麻毒素A链蛋白。这项研究的更广泛影响是多方面的。虽然所提出的大部分工作都是基础性的，即选择中使用的目标分子，但蓖麻毒素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武器中使用包括A链的蓖麻毒素的担忧加剧。此外，所开发的构建集成分子传感器的方法也可以应用于许多其他目标。通过本研究，可以实现临床和野外使用的功能传感器。从事这个项目的学生将接触到广泛的技术，包括化学合成、分子生物学和光学光谱学。除了预期的学年努力外，研究生导师和本科生将被招募到一个特别的暑期研究团队，该团队将在一个高度协作的多学科环境中工作十周。

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.