A novel, noninvasive way of watching genes at work could help researchers make new drugs faster and learn more about biological processes.
Carnegie Mellon University biologist Eric Ahrens and his team devised a technique that gets cells to produce their own contrast agents, making them easily visible with magnetic resonance imaging.
The contrast essentially puts the gene being studied in the spotlight on an MRI scan.
"We developed a marker that we can attach to the gene of interest," Ahrens explained. "When the gene of interest is turned on in the cell, the marker is turned on. Then we can visualize that with MRI."
The findings appear in the April issue of the journal Nature Medicine.
It's a clever approach, said Joseph Glorioso, chairman of molecular genetics and biochemistry at the University of Pittsburgh School of Medicine. "A lot of people will use it," he predicted, noting no other good way exists to image cells or genes that have been transferred to cells in the body.
Scientists typically tag a gene with a fluorescent protein or other markers to check for activity, or what scientists call expression, but that requires removing the tissue to see what happened.
"These types of things are performed outside of the body," Ahrens said. "And they involve using some sort of optical microscopy to read out the gene expression."
The MRI procedure leaves tissues intact, making it possible to follow genes in the same cells over time. It also allows a look into regions, such as deep within the brain, that are otherwise hard to reach.
It works like this:
The gene to be studied is joined to the "reporter" gene, which makes a protein with an iron core. To make this protein, the gene uses iron from the body's own stores, which contain "about as much iron as a large construction nail," Ahrens said.
When the gene being studied is active, the MRI reporter gene makes the metalloprotein.
An MRI scanner generates radiofrequency pulses and a magnetic field, which in turn causes fluctuation in the hydrogen atoms in the numerous water molecules in the body. The scanner translates these fluctuations to produce vivid images of body structures. The metalloprotein produced by the reporter gene acts like a tiny magnet, influencing water molecules nearby and emitting a signal that, like contrast dye, shows up as a dark area on the MRI image.
From the scan, scientists can answer questions like "where did [the study gene] go, when was it turned on, if it even worked at all, and how long did it work for," Ahrens said.
The reporter and study genes could be carried into cells by a virus or another so-called vector. Or, researchers could breed lab animals that carry the reporter gene where they want it.
Ahrens plans to develop animals that have the reporter gene linked to genes in neurons, so that he can see the impact of a drug or physical stimulus on the cells.
The technique has many possible applications, Ahrens said. For instance, the reporter gene potentially could be used to assess whether a gene that targets cancer is activated in diseased cells.
"This is important for the pharmaceutical industry, for molecular medicine, for basic genetics," he said.