Caged-Degron Feedback Circuits for Autonomous Signaling Control
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Solution Overview
Problem
Existing engineered cells lack the ability to modulate their output without continuous external input, necessitating repeated user intervention for adjustments.
Innovation Solution
Molecular feedback circuits employing caged-degrons that allow for self-regulation of cellular activities by integrating caged-degrons into signaling pathways, enabling feedback-controlled modulation of cellular output.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If repeated external inputs are used to control cellular output, then desired regulation of cellular activities is achieved, but continuous user intervention is required
Solution Approach 1:
The patent implements feedback control by engineering cells to sense their own output levels and automatically adjust their behavior accordingly. The cell measures its output (such as metabolite concentration or product formation rate) and uses this information to regulate its own activity, creating a closed-loop control system that eliminates the need for continuous external intervention
Solution Approach 2:
The engineered cell performs self-regulation by integrating sensing and actuation capabilities within the same cellular system. The cell autonomously monitors its own state and adjusts its metabolic pathways or gene expression without requiring external control inputs, effectively serving itself rather than requiring continuous user management
2Adaptability or versatility
If external stimuli are used to adjust engineered cell output, then modulation of cellular function is achieved, but continuous external input is necessary
Solution Approach 1:
The patent creates autonomous feedback circuits within engineered cells that allow the cell to sense its output and automatically adjust its behavior. The feedback mechanism enables the cell to modulate its own function based on real-time measurement of its performance, eliminating the need for continuous external stimuli while maintaining adaptability
Solution Approach 2:
The engineered cell incorporates dynamic regulation mechanisms that allow it to adapt its behavior in response to its own state. The cell uses adjustable parameters such as gene expression levels, enzyme activity, or metabolic flux that can be dynamically modified through internal feedback control, providing versatility without requiring external intervention
Data Source
AI summary
Provided are molecular feedback circuits employing caged-degrons. Aspects of such circuits include the use of a caged-degron to modulate the output of a signaling pathway in a feedback-controlled manner. Also provided are nucleic acids encoding molecular circuits and cells containing such nucleic acids. Methods of using caged-degron-based molecular feedback circuits are also provided, including e.g., methods of modulating a signaling pathway of a cell that include genetically modifying the cell with a caged-degron-based molecular feedback circuit.