Researchers at the University of California, Santa Barbara have developed a new genetic sensor that enables MRI machines to detect molecular activity inside cells. This technology could allow scientists to better study diseases such as cancer, neurodegeneration, and inflammation by observing changes at the molecular level rather than waiting for structural alterations in tissues.
Arnab Mukherjee, associate professor of chemical engineering at UC Santa Barbara, explained the current limitations of MRI: “You can see the structures of your tissues — whether it’s the brain, the heart, the kidneys or the stomach — but you don’t get molecular information. So, the only time you can know that something is going wrong or something has changed is if you take another MRI, and the structure and morphology of the tissue changes.” He added that for many diseases, structural changes may not appear until after significant progression.
Mukherjee began pursuing this research during his postdoctoral work at Caltech. His goal was to improve MRI technology so it could capture real-time molecular-level changes. “If we can see these molecular-level changes happening in real time, then we can ask questions like, ‘How do tumor cells metastasize?’ or ‘How does neurodegeneration progress at the molecular level as an animal ages?’ There’s currently no way to do that,” he said.
The team used synthetic biology concepts to design a protein-based sensor that can be genetically engineered into cells. This allows MRIs to visualize various cellular processes. The modular nature of their sensor means researchers can customize it by attaching different proteins targeting specific cellular activities. Their findings were published in Science Advances.
The sensor works by utilizing aquaporin—a protein channel in cell membranes—to control water movement across cells. Since water molecules act like tiny magnets within an MRI’s magnetic field, altering their movement makes it possible for MRIs to detect specific biological processes with greater detail than before. “If you can control or affect the rate at which water molecules move back and forth across the cell, you can make that magnetic signal specific to certain types of cells or biological processes,” Mukherjee explained.
Graduate student Asish Ninan Chacko contributed by fine-tuning this system so different chemical signals could regulate it: “We can even replace this particular protease with another type of protease, and use it to detect many different processes.”
Their modular system—named MAPPER (modular aquaporin-based protease-activatable probes for enhanced reporting)—enables researchers to monitor multiple chemical events inside living cells using one setup. Chacko noted: “That’s a first in this paper because so far in the scientific literature, you’ve seen only four or five genetic sensors… In this paper we describe close to ten systems we can detect with this one setup.”
The tool may also reduce reliance on animal sacrifice in laboratory studies since continuous imaging becomes possible throughout disease progression instead of relying on single snapshots from separate animals.
Mukherjee hopes other scientists will adopt MAPPER for diverse applications: “We want to take these sensors and put them in the hands of people who will actually use them,” he said. “Whether that’s neuroscientists…or developmental biologists…”
