2025/01/02 by Xiaoyu Yang, Jason W. Rocks, Kaiyi Jiang +9 · 1 voice · 2 citations
Biochemistry, Genetics and Molecular Biology · #Receptor Mechanisms and Signaling #Single-cell and spatial transcriptomics #Gene Regulatory Network Analysis
paper · doi:10.1126/science.adm8485
openalex publication_date 2025/01/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial phosphorylation networks in which reversible enzymatic phosphorylation cycles were assembled from modular protein domain parts and wired together to create synthetic phosphorylation circuits in human cells. Our design scheme enabled model-guided tuning of circuit function and the ability to make diverse network connections; synthetic phosphorylation circuits can be coupled to upstream cell surface receptors to enable fast-timescale sensing of extracellular ligands, and downstream connections can regulate gene expression. We engineered cell-based cytokine controllers that dynamically sense and suppress activated T cells. Our work introduces a generalizable approach that allows the design of signaling circuits that enable user-defined sense-and-respond function for diverse biosensing and therapeutic applications.