Collaborative Research: Mechanisms of Hybridization Kinetics in DNA Surface Layers

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This award by the Biomaterials Program in the Division of Materials Research to Polytechnic University and to Columbia University is to study "Mechanisms of Hybridization Kinetics in DNA Surface Layers." These collaborative proposals combined experimental and theoretical approaches, and will seek to understand the mechanisms governing competitive surface hybridization, where two different nucleic acid types, one a complementary and the other a mismatched sequence, are present in solution and compete for binding to a single type of immobilized strand on a solid surface. Through this process, the genomic and genetic information contained in the sample is identified and quantified for numerous applications: to study gene function, to identify the genotype of individuals, to perform forensic analysis, to carry out comparative genomic studies across species, or to support other genodiagnostic needs that require quantification of information from nucleic acid molecules. Understanding the complex, dynamic evolution of the competing hybridization reactions occurring during such a measurement is essential both to experimental design and to data analysis. Electrochemical techniques will be used to monitor kinetics of surface hybridization reactions. In parallel and in close interaction, a theoretical effort will develop kinetic models that integrate microscopic theories of reaction rate "constants" needed to analyze and interpret the experimental data. These prototypic studies will then be extended to more complex systems characterized by greater diversity of sequences. This program is expected to contribute to the development of a technologically and scientifically knowledgeable workforce by training individuals at different stages of learning, from high school through graduate school.Presently the powerful, yet problematic, technologies of surface hybridization lack the firm footing required for clinical applications. The knowledge this project will provide will be especially crucial to healthcare applications such as personalized medicine, where accurate determination of a patient's genetic makeup (genotype) can provide vital lifesaving capability. The program will seek outstanding high school students for summer research in coordination with the New York Academy of Sciences and other local high school outreach programs. The program will also engage undergraduate and graduate students in collaborative research encompassing experiment and theory that will introduce team research skills, provide broad exposure to laboratory, modeling, and theoretical methods, and stimulate career interest at the highly critical interface between chemical, biomaterial, and surface engineering and biotechnology. Educational electronic "research stories" will be posted on the PIs' websites in a format accessible to broad audiences. The program will also enrich institutional curricula, including creation of a lecture-laboratory hybrid course in Biointerfacial Engineering at Polytechnic University.