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Synthetic NF‐kB: a Building Approach to Study Complex Signaling Behaviors
Author(s) -
Wei Ping
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00184
Subject(s) - signal transduction , redundancy (engineering) , systems biology , neuroscience , cell signaling , synthetic biology , biology , microbiology and biotechnology , computational biology , computer science , operating system
Quantitative features of cellular signaling behaviors have drawn much attention due to their capabilities to carry extra information to regulate comprehensive downstream gene expression, and thus determine dramatically different cell fates. Remarkably, such quantitative signaling behaviors were often oscillatory or pulsatile. The particular properties of oscillatory signaling dynamics (e.g., amplitude, frequency) have shown great benefit to coordinate or differentially regulate gene expression in stress signaling and inflammatory response. Due to the complexity and redundancy in natural cells, it remains challenging to completely understand how the complex temporal behaviors are programmed in parameters or structures of the signaling circuits. Here, we took a synthetic approach to study the underlying principles of such complex signaling behaviors, via a reconstituted human nuclear factor κB (NF‐κB) system in S. cerevisiae . This synthetic NF‐κB signaling circuit can robustly oscillate with extensive tunability, which allows us to systematically explore the signaling capabilities by tuning the circuit structures and parameters. Our synthetic NF‐κB represents a general inhibitor‐transcriptional factor model design. The principles revealed in this synthetic system could facilitate our understandings in similar natural signaling systems.