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The majority of biomolecular reactions in living cells are precisely organized by phase or location yet are not directly involved in metabolism, synthesis, or detection. These reactions are conserved and essential for life; they play critical roles in cell function. This observation suggests how designing reactions of this type might analogously dramatically enhance the performance of engineered sensors or catalysts. Inspired by this idea, we have been designing reaction systems in which biomolecular sensors or catalysts are coupled to processes that regulate, amplify, and drive them. We recently developed aptamer-regulated transcription for in vitro sensing and transduction (ARTIST), in which the binding of a target species and an aptamer modulates the rate of production of RNA in a test-tube reaction by binding a target species and an aptamer. The RNA produced is further processed by downstream reactions that amplify and filter sensor outputs, allowing us to design reliable and robust digital threshold sensors and sensitive "thermometers" for a range of molecular and biomolecular targets of physiological and environmental interest. Similarly, we have developed a generic method for creating a molecular cofactor that can increase catalytic flux by reducing or eliminating product inhibition and demonstrate this mechanism on a highly specific RNA catalyst. We also find that reaction flux can be further enhanced in a multiphase reaction when the catalyst and its cofactor are each localized to different biomolecular liquids. I will end by considering more generally the opportunities involved in designing multiple biomolecular reaction networks that involve reactions and diffusion. Understanding the dynamics and information flow in multiphase reaction-diffusion systems could help us tackle grand challenges such as hierarchical self-assembly or precisely orchestrating multistep synthesis in a single reaction vessel.
Rebecca Schulman, Ph.D.
Johns Hopkins University
Kent Gordon Croft Investment Management Faculty Scholar
Associate Professor of Chemical and Biomolecular Engineering