Geneticists Create ‘Bi-Fi’ – The Biological Internet

Scientists have engineered a groundbreaking system that uses a virus called M13 bacteriophage to create a biological internet, or “Bi-Fi,” enabling cells to communicate with each other by exchanging genetic information. This innovation opens new possibilities for controlling biological processes inside living organisms with unprecedented precision.

What Is M13 and How Does It Work?

M13 is a harmless filamentous virus that infects Escherichia coli bacteria without killing them. Unlike many viruses that destroy their hosts, M13 quietly replicates inside the bacteria and releases new virus particles continuously, allowing long-term interaction with its host. The virus’s structure is like a tiny thread, with its DNA wrapped in thousands of copies of a protein coat. Scientists can modify this coat to display specific molecules on the virus surface, making M13 a versatile tool for biotechnology.

Engineering a Biological Internet

Researchers at Stanford and other institutions have repurposed M13 to transfer genetic “messages” – pieces of DNA encoding instructions – from one bacterial cell to another. These messages are packaged inside the virus particles, which infect recipient cells carrying the right receptor. This system allows cells to share complex genetic information, enabling coordinated behavior across bacterial communities.

By combining M13-mediated communication with CRISPR interference (CRISPRi), a powerful gene regulation tool, scientists have built synthetic bacterial consortia that can perform complex logic operations. For example, groups of engineered E. coli cells can process multiple inputs and make decisions collectively, much like a computer network. This “Bi-Fi” system achieves efficient and sensitive communication, surpassing traditional methods like quorum sensing.

Key Discoveries and Features

– Self-Jamming Immunity: The M13 phage produces an extracellular factor that protects uninfected bacteria by reducing infection rates by about 70%. This “self-jamming” mechanism helps maintain a balance between infected and uninfected cells, ensuring long-term stability of the bacterial community and the communication network.

– Mathematical Modeling: Detailed models based on chemical reaction networks capture how bacterial growth phases, cell density, and resource availability affect phage secretion and infection. These models help predict and optimize communication dynamics in real biological environments.

– High Transfer Efficiency: The system can transfer genetic messages with over 97% efficiency within hours, enabling rapid and reliable information exchange.

– Modularity and Control: Different genetic messages (such as single guide RNAs for CRISPRi) can be swapped easily, and the transfer can be chemically induced or blocked, allowing precise control over the communication.

Practical Applications

This biological internet has promising applications across multiple fields:

– Synthetic Biology and Biocomputing: By distributing complex genetic circuits across different bacterial strains, researchers can create living systems that perform sophisticated computations, biosensing, and decision-making.

– Biomanufacturing: Engineered bacterial communities can coordinate production of valuable compounds more efficiently by communicating genetic instructions.

– Microbiome Engineering: The system could be used to control and manipulate microbial populations in environments like the human gut, improving health and disease treatment.

– Targeted Therapeutics: Modified M13 phages can deliver therapeutic genes or molecules to specific cells, potentially enabling new treatments for infections or cancer.

– Biosensing and Diagnostics: M13-based sensors can detect harmful chemicals or pathogens with high sensitivity.

Why Is This Important?

Creating a biological internet inside living cells represents a major leap forward in biotechnology. It allows scientists to program cells to work together as a network, sharing information and coordinating actions in ways previously impossible. This could revolutionize how we design living medicines, environmental sensors, and biofactories.

In essence, the engineered M13 phage system transforms cells into communicating nodes of a living network, opening the door to a future where biological systems can be programmed and controlled with the sophistication of digital technology – a true “Bi-Fi” for the biological world.

Read More
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[2] https://www.biorxiv.org/content/10.1101/2022.05.11.491355v2.full.pdf
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[4] https://www.biorxiv.org/content/10.1101/2022.05.11.491355v2.full-text
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