Engineering synthetic phosphorylation signaling networks in human cells

Area of Science:

• Cellular biology
• Synthetic biology
• Biochemistry

Background:

• Protein phosphorylation networks are crucial for cellular signal transduction and environmental responses.
• Existing methods for engineering cellular signaling are limited in scope and tunability.

Purpose of the Study:

• To engineer artificial phosphorylation networks in human cells.
• To create customizable synthetic signaling circuits with user-defined sense-and-respond functions.
• To develop cell-based controllers for therapeutic applications.

Main Methods:

• Assembled reversible enzymatic phosphorylation cycles from modular protein domains.
• Wired these modules into synthetic phosphorylation circuits in human cells.
• Coupled synthetic circuits to cell surface receptors and gene expression regulators.

Main Results:

• Successfully engineered artificial phosphorylation networks with tunable functions.
• Demonstrated the ability to create diverse network connections for sensing and response.
• Developed cell-based cytokine controllers that can sense and suppress activated T cells.

Conclusions:

• Introduced a generalizable approach for designing synthetic signaling circuits.
• Synthetic phosphorylation circuits enable precise control over cellular functions.
• This technology has broad potential for biosensing and therapeutic applications.