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Sensing and Reprogramming Surface Receptor Activation With Synthetic Transcriptional Circuits.

Fei Liu1, Mei Yuan1, Li-Juan Tang1

  • 1State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, Hunan University, Changsha, P. R. China.

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Summary
This summary is machine-generated.

Scientists developed a synthetic receptor-signalling induced transcription (RESIT) circuit to reprogram cell surface receptor activity. This versatile system enables sensing and controlling cellular functions for therapeutic applications.

Keywords:
RTK activitybiosensorscell‐specific therapysurface receptor activationsynthetic biology

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Area of Science:

  • Synthetic biology
  • Molecular and cellular biology
  • Biochemistry

Background:

  • Cell surface receptors are crucial for cellular processes.
  • Engineering synthetic circuits to control receptor activity is challenging.

Purpose of the Study:

  • To develop a novel synthetic genetic circuit for sensing and reprogramming membrane receptor activation.
  • To enable user-defined transcriptional programs based on receptor signaling.

Main Methods:

  • Developed the receptor-signalling induced transcription (RESIT) circuit.
  • Utilized receptor activation-mediated split protease complementation.
  • Engineered membrane-tethered synthetic transcriptional modules.

Main Results:

  • Demonstrated RESIT's applicability with various transcription factors and split proteases.
  • Applied RESIT to probe Ca2+ entry, PIEZO1 induction, T cell activation, oncogenic RTK activity, and Ras activation.
  • Repurposed RESIT for therapeutic functions like apoptosis induction and T cell activation.

Conclusions:

  • The RESIT system offers a modular and versatile platform for interrogating juxtamembrane signaling.
  • RESIT can effectively rewire receptor activation to achieve desired therapeutic outcomes.