Biomolecular Feedback Circuits for Modular, Robust and Rapid Response
This is a joint project with Steve Mayo, funded by the ARO Institute for Collaborative Biotechnology.
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Current participants:
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Collaborators
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Objectives
 Block diagram of the proposed control architecture. The (slow) transcriptional regulation is used to maintain an appro- priate concentration of protein whose activity can be modulated via a conformation change. An allosteric regulation mechanism is then used to produce an active protein (or protein complex) at a much faster timescale. The protein must both have the desired function (e.g., fluorescence) and allow a mechanism to compare its concentration to that of a reference species (inducer). |
We are working to develop a new class of 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 is to make use of biological processes that operate on timescales of seconds to minutes, primarily through feedback mechanisms using allosteric and covalent modifications that affect protein function. We are exploring the use of the modularity of protein domains to design circuit elements that can be reused more easily than existing components, and we will test our circuits across a variety of cellular contexts to assess robustness as a fundamental property of the design.
Specific objectives for the first year of the project include:
- Construct and characterize a baseline design using transcriptional regulation, for comparison to future circuits and also to provide a source of data for model verification.
- Design and model a circuit that follows the concentration of an inducer and characterize the performance of that circuit using deterministic and stochastic simulations
- Demonstrate modulation of protein activity via a chemical signal based on previously published work
- Design and prototype simple modular linkers that can be used as a first step for creating functional protein switches.
