Uncovering the potential of genetic circuits on single DNA molecules

Uncovering the potential of genetic circuits on single DNA molecules

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A genetic circuit on a single DNA molecule as an autonomous dissipative nanodevice. Credit: Nature Communications (2024). doi: 10.1038/s41467-024-45186-2.

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A genetic circuit on a single DNA molecule as an autonomous dissipative nanodevice. Credit: Nature Communications (2024). doi: 10.1038/s41467-024-45186-2.

In new Nature Communications In this study, researchers explore the construction of genetic circuits on single DNA molecules, demonstrating in situ protein synthesis as a guideline for dissipative nanodevices, and providing insight into the design of artificial cells and nanobiotechnology applications.

The term “genetic circuit” is a metaphorical description of the complex network of genetic elements (such as genes, promoters, and regulatory proteins) within a cell that interact to control gene expression and cellular functions.

In the field of artificial cell design, scientists aim to replicate and engineer these genetic circuits to create functional, self-sufficient units. These circuits function as a molecular mechanism responsible for regulating cellular processes by finely regulating the production of proteins and other molecules.

By understanding and manipulating these circuits, researchers can engineer artificial cells with programmable behaviors that mimic the functions of natural cells.

In the context of the aforementioned study, the focus was on building genetic circuits on single DNA molecules. This represents a novel approach as it moves away from the traditional cellular context and explores the possibility of creating gene circuits in cell-free conditions.

First author Dr. Ferdinand Grace of the Weizmann Institute of Science in Israel explained the researchers’ motivations to Phys.org: “We are trying to reconfigure biological processes outside the complex circuits of living cells, and we hope to improve our understanding of nature’s guiding principles. The research is directed toward building future artificial cells, and could “Single DNA molecules are the genetic basis for this.”

Gene regulation

Gene regulation is the process by which cells control the expression of genes, determining when and to what extent gene information is used in the synthesis of functional molecules such as proteins or RNA. It plays a crucial role in maintaining cellular functions, responding to environmental changes, and ensuring proper development.

Regulation of gene expression involves transcription and translation. During transcription, a specific segment of DNA serves as a template for the synthesis of complementary mRNA molecules by RNA polymerase. This messenger RNA carries the genetic code from the nucleus to the cytoplasm, where translation takes place.

Translation involves converting mRNA into proteins. Ribosomes read the mRNA sequence, facilitating the assembly of amino acids into a polypeptide chain, forming the protein encoded by the gene.

“In prokaryotic systems, the processes of transcription and translation are coupled. This means that once RNA polymerase produces mRNA from DNA, the ribosome can find a ribosome-binding site on the nascent mRNA to begin protein synthesis. The nascent protein can fold and function.” While It remains bound to DNA by the RNA polymerase-mRNA-ribosome complex. After transcription or translation ends, the nascent protein falls off the DNA and diffuses into the bulk solution,” explained co-author Dr. Shirley Shulman-Dub of the University of California at Weizmann Institute of Science in Israel.

The importance lies in the increased local concentration of nascent proteins, which is approximately 1000 times higher than in the surrounding bulk solution. This spatial organization and enhanced concentration could have implications for cellular functions, and may play a role in constructing artificial cells using single DNA molecules.

more information:
Ferdinand Gris et al., Genetic circuit on a single DNA molecule as an autonomous dissipative nanodevice, Nature Communications (2024). doi: 10.1038/s41467-024-45186-2

Magazine information:
Nature Communications

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