ITR: Solution Phase Computation with Enzymatic Networks

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AbstractAugust 7, 2003ITR: Solution Phase Computation with Enzymatic NetworksDarko StefanovicColumbia University03248845Communication between oligonucleotide-scale logic gates based on phosphodiesterase and ligase enzymatic reactions as well as nanoparticle beads is being investigated in order to achieve scalable and robust molecular computation that can be applied to contol of autonomous molecular devices. In particular, medium-scale feedforward (cascaded) and feedback circuits and programmable arrays are being designed and evaluated in the laboratory. The circuits being developed include oscillators, clocks, flip-flop memories, and counters with internal error correction. Applications of these circuits for engineering properties of cells are being investigated. Flow-cytometry is being used to develop methodology that will be able to analyze massively parallel networks of individual computation elements.Through this work, which is interdisciplinary, and involves circuit design, mathematical modeling, and laboratory work, the engineering principles needed to synthesize large-scale molecular circuits for in vitro computations and small circuits for intracellular and in vivo applications are being developed. Foundations are being laid for applications of these circuits in molecular autonomous devices which can analyze the environment and respond in preprogrammed fashion to changes in environment. The computational strategy which will be implemented in complex networks of digital logic circuits-will find application in the design of various sorts of synthetic cellular systems.A new generation of students from computer science and biochemistry is being trained to understand and appreciate the problems and approaches of both disciplines. Also, high-school students are being introduced through participation in this project to advanced scientific concepts.