This 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.
