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Efficient Sampling of Genetically Encoded Biosensor Design Space Enabled with a Design of Experiments and Automation Workflow
Published on: October 17, 2025
TRADEOFFS IN ADAPTING BIOLOGICAL SYSTEMS
Rajat Bhatnagar1,2, Hana El-Samad1,2
1Department of Biochemistry and Biophysics, California Institute for Quantitative Biosciences, University of California at San Francisco, 1700 4th Street, San Francisco CA 94158.
Abstract:
Biological systems must sense and adapt to changes in their environment. Molecular networks capable of such adaptation belong to two well-known classes, feed-forward and feedback structures, but the fundamental limitations and tradeoffs of these two classes remain unknown. Here we study the advantages and limitations of the feedforward class using three-node circuits representative of these architectures. The feedforward model we investigate displays a tradeoff between the sensitivity of the response (its peak response) and its precision (its error in its return to steady-state). We suggest two ways in which this tradeoff can be alleviated: (1) by introducing a nonlinearity in the production of a specific node in the network, or (2) by adding a feedback loop to the input. We present analytical and numerical examples to support our findings.
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