Murray & Mayo - Biomolecular Feedback Circuits for Modular, Robust and Rapid Response
Bio-Inspired Network Science
Figure Caption: Scaffold-based circuit for maintaining relative concentration. The circuit consists of a synthetic scaffold (SC) protein that co-localizes a histidine kinase (HK) and a response regulator (RR), facilitating rapid phos-phorylation of the rate regulator. The phosphorylated rate regulator activates transcription of an anti-scaffold protein (AS), which binds competitively to the scaffold, preventing activation of the rate regulator by the histidine kinase via sequestration.
We are developing a new class of biomolecular feedback circuits that makes use of synthetic biological components to implement rapid response to input signals in a more robust and modular fashion. Our approach makes use of biological processes that operate on timescales of seconds to minutes, primarily through allosteric and covalent modifications that affect protein function. We exploit the modularity of protein domains to design circuit elements that can be reused more easily than existing components, are testing our circuits across a variety of cellular contexts to assess robustness as a fundamental property of the design.