Gene expression is the process by which the DNA of genes is used to produce proteins that perform essential roles as enzymes, hormones, antibodies, and more. However, this complex process is not fully understood because it varies dramatically due to environmental factors, developmental stages, and diseases. We’d like a better understanding of gene expression, but finding a system that allows it to be studied free of extraneous influences has been difficult.
Researchers may have overcome this obstacle with the development of a biochip that contains an array of artificial “cells” that enable the precise study of how gene expression changes with time. This system could be used to investigate how different cells change their activity as development proceeds or in response to environmental changes.
The biochip was constructed by assembling bundles of DNA on the surface of circular silicon compartments (50 μm radius and 1-3 μm height). Thin capillaries were used to connect DNA compartments to a channel that provided nutrients and energy. Researchers were able to observe stable gene expression and expression patterns that changed over time by tracking the presence of green fluorescent protein (GFP) expressed from the DNA.
When the DNA bundles contained a gene that encodes GFP, the green glow showed a sharp onset after a two-hour delay, with steady-state levels reached in about eight hours. To look at more complex gene expression, the researchers put in the genes for a network of activators and repressors. Oscillatory gene expression dynamics, where GFP levels cycle through peaks and declines over 2.5 hours, were tracked via its green glow.
Embryonic development is dependent on spatial arrangement of cells and their communication with one another, which occurs through the time-dependent release of proteins regulated via gene expression. This behavior is often termed reaction-diffusion, as a reaction (gene expression) is followed by the diffusion of the product (a protein) away from the site of the reaction.
Researchers performed several reaction-diffusion experiments to demonstrate that this biochip can be used to model an embryo. They altered the dynamics of these systems by varying capillary lengths and geometry, which changes the time it takes for the proteins to spread away from the site where they’re made. Diffusion-based communication between DNA compartments, similar to that required in a growing embryo, was also demonstrated using an activator-repressor system, which created pulses of GFP that appeared in two compartments spaced 50 to 300 µm from one another.
With this new device, researchers may finally have the tool they’ve needed to obtain a clear picture of gene expression, which should help them with predictions and theoretical modeling of programmed gene expression and biological systems such as the embryo. The biochip has opened a door for the potential to reveal information that could lead to a new understanding of how normal gene expression—and how errors in that process can lead to diseases.
Listing image by Mayo Clinic Gene Expression Core