CAREER: Nucleic acid circuitry for programming gene expression

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0954566SeeligThe proposed work will enable a potentially transformative technology for controlling cellular behavior using nucleic acids. The PI will engineer synthetic molecular circuitry that can analyze RNA expression inside living cells and { based on this analysis { autonomously control gene expression. The PI will show that nucleic acid circuitry can distinguish between di_erent cell types and states and can specifically regulate a target gene only in a subset of cells. A central aim of this project is to increase the specificity of conventional antisense and siRNA-based therapeutics by combining drug delivery with sensing and logic. Specific research objectives are: (i) The design of hybridization-based molecular sensors for the detection of RNA in living cells; (ii) the design of controllable molecular actuators based on antisense oligonucleotides and silencing RNA; (iii) the construction of integrated sensor-actuator systems for conditional gene regulation. This program provides the basis for the construction of complex multi-component circuits for programmable control of gene expression. This work will lead to new molecular tools for temporal and spatial control of gene expression, with the potential for wide-spread applications in disease therapy and in basic biology research. The proposed research is tightly integrated with an outreach program with two main aims. The first aim is to develop an educational framework that teaches the interdisciplinary skills required to succeed in synthetic biology research. The second aim is to leverage this framework to attract and engage students who are not traditionally involved with life-science research, or would not consider enrolling in one of the traditional tracks in an electrical engineering or computer science program (the PI's home departments are EE and CS).