Computer-Engineered DNA to Study Cell Identities
Published:23 Apr.2024 Source:Max Delbrück Center for Molecular Medicine in the Helmholtz Association
A new computer program allows scientists to design synthetic DNA segments that indicate, in real time, the state of cells. Now, scientists at the Max Delbrück Center have created an algorithm that can design such tools that reveal the identity and state of cells using segments of DNA called "synthetic locus control regions" (sLCRs). They can be used in a variety of biological systems. "This algorithm enables us to create precise DNA tools for marking and studying cells, offering new insights into cellular behaviors," says Gargiulo, senior author of the study. They hope this research opens doors to a more straightforward and scalable way of understanding and manipulating cells.
This tool allows researchers to examine the way cells transform from one type to another. It is particularly innovative because it compiles all the crucial instructions that direct these changes into a simple synthetic DNA sequence. In turn, this simplifies studying complex cellular behaviors in important areas like cancer research and human development. The computer program is named "logical design of synthetic cis-regulatory DNA" (LSD). The researchers input the known genes and transcription factors associated with the specific cell states they want to study, and the program uses this to identify DNA segments (promoters and enhancers) controlling the activity in the cell of interest. This information is sufficient to discover functional sequences, and scientists do not have to know the precise genetic or molecular reason behind a cell's behavior; they just have to construct the sLCR.
Scientists can then make a tool, called a "synthetic locus control region" (sLCR), which includes the generated sequence followed by a DNA segment encoding a fluorescent protein. "The sLCRs are like an automated lamp that you can put inside of the cells. This lamp switches on only under the conditions you want to study," says Dr Michela Serresi, a researcher at the Gargiulo lab and co-first author. The color of the "lamp" can be varied to match different states of interest, so that scientists can look under a fluorescence microscope and immediately know the state of each cell from its color. "We can follow with our eyes the color in a petri dish when we give a treatment," Serresi says.