NSF-BSF: Design of Batch Biochemical Oscillators

University Of Colorado At Boulder, Boulder CO

Investigators

Abstract

Oscillators are important to life. They regulate cellular metabolism and control heartbeat, intestinal contractions, and circadian rhythm. This project develops tunable, nontoxic biochemical oscillators. Their behavior in cell-like systems will be studied. It will provide tools for assembling cell-like structures with adjustable dynamic outputs. It could also facilitate the construction of new varieties of devices. A summer biotechnology training program for high school students will be expanded. A modest core facility for droplet microfluidics will be constructed. Finally, a new international partnership focused on the analysis and design of nonlinear biochemical systems will be supported. This project departs from contemporary analyses of out-of-equilibrium reactions that require toxic inorganic catalysts or sustained flows by building biochemical reaction networks that can produce repeated oscillations in small compartments (e.g., droplets). It will develop reagents for building and monitoring batch biochemical oscillators, a kinetic framework (i.e., mechanistic models) for modeling and adjusting oscillatory dynamics, microfluidic methods for preparing and studying multi-oscillator systems, and new designs for the controlled release of functional molecules in complex biological matrices. The ultimate goal of this work is to develop stable, experimentally tractable biochemical oscillators that exhibit predictable dynamics in a broad set of environments. If successful, it could provide a starting point for developing new varieties of protocells, biomimetic materials, and cell-interfacing systems (e.g., drug-delivery vehicles or cellular controllers). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.