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Engineering intelligent chassis cells via recombinase-based MEMORY circuits.

Brian D Huang1, Dowan Kim1, Yongjoon Yu1

  • 1Georgia Institute of Technology, School of Chemical & Biomolecular Engineering, 311 Ferst Drive, Atlanta, GA, 30332-0100, Georgia.

Nature Communications
|March 19, 2024
PubMed
Summary
This summary is machine-generated.

Synthetic biologists created intelligent Escherichia coli strains with programmable memory, decision-making, and communication. This breakthrough unifies three intelligence tenets in a single living system for advanced synthetic biology applications.

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Area of Science:

  • Synthetic Biology
  • Genetic Engineering
  • Systems Biology

Background:

  • Achieving unified intelligence (decision-making, communication, memory) in living systems remains a challenge.
  • Existing technologies address individual aspects of intelligence but lack integration.
  • Engineering complex cellular behaviors requires robust genetic tools.

Purpose of the Study:

  • To engineer a synthetic cell chassis capable of exhibiting all three tenets of intelligence.
  • To develop a platform for programmable and inheritable genetic modifications.
  • To demonstrate information exchange between engineered and native bacteria.

Main Methods:

  • Engineered Escherichia coli strains harboring six orthogonal and inducible genome-integrated recombinases (MEMORY platform).
  • Utilized recombinase functions for DNA inversions, deletions, and insertions.
  • Demonstrated programmable gain/loss of function and sequential reprogramming of DNA circuits.
  • Showcased inter-bacterial communication using a probiotic MEMORY strain (Nissle 1917) and Bacteroides thetaiotaomicron.

Main Results:

  • Successfully created MEMORY chassis cells integrating decision-making, communication, and memory.
  • Achieved programmable and permanent genetic modifications without compromising the MEMORY platform.
  • Demonstrated sequential programming and reprogramming of cellular functions.
  • Established information exchange between engineered E. coli and native gut bacteria.

Conclusions:

  • The MEMORY platform represents a significant advancement in engineering intelligent living systems.
  • This work unifies key aspects of cellular intelligence within a single, programmable biological chassis.
  • The engineered probiotic strain holds potential for therapeutic applications and understanding host-microbe interactions.