In the field of Synthetic Biology, biological systems are engineered to sense inputs and respond in a programmed manner, a process called biological computing. Traditional biocomputing faces limitations due to the resource burden on single engineered cells, restricting the amount of foreign DNA they can simultaneously express. A recent solution, distributed biological computing, involves using a community of cells to divide large computational tasks. However, this approach introduces a communication challenge, as cells in the community lack sufficient unique (orthogonal) molecular signals for coordination.
To address this, we have developed a novel communication system for Escherichia coli cells that uses engineered bacteriophages encoding guide RNA genes. These bacterial viruses transfer DNA messages between bacterial cells in a process termed “intercellular CRISPRi” (i-CRISPRi). Our approach combines phage-mediated DNA transfer with CRISPR interference (CRISPRi), a method for controlling gene expression. By employing programmable DNA messages, the system can generate diverse signals with specific instructions, enabling high-bandwidth and fast communication between cells.
We demonstrated the capability of i-CRISPRi by building eight unique DNA signals and creating bacterial consortia that execute intercellular digital logic gates, such as NOT, YES, AND, and AND-AND-NOT. These consortia involved up to seven distinct bacterial cells, showcasing how distributed computation can be deployed for complex biocomputing tasks. Key findings highlighted that the efficiency of communication depended on the growth phases of both sender and receiver bacteria, and resource competition between them.
This innovative method not only enhances the ability of bacterial communities to perform complex computations but also establishes a foundation for building larger, more intricate biological circuits. These circuits resemble interconnected computer networks, offering new possibilities in biological computing.
Contact:
Links:
- Link to the article in Nucleic Acids Research
- Link Scoop.it Life Science Université Paris-Saclay
