Rice bioengineer Laura Segatori and her Brown School of Engineering team have received a prestigious National Institutes of Health Research Project Grant to develop gene activity sensors and activators that, she said, hold unprecedented opportunities for treating diabetes, cancer, infectious diseases, and genetic disorders.
The four-year, $1.8 million grant is administered by the National Institute of Biomedical Imaging and Bioengineering. It follows a smaller National Science Foundation grant in January that suggested the Segatori lab’s strategy for engineering cellular devices can be applied to virtually any cellular process associated with a transcriptional response.
The idea is to program mammalian cells to read their environment and develop living designer systems that detect and correct human pathologies. While the concept isn’t new, Segatori’s approach, built on the back of a novel system introduced last year to improve detection of target gene expression, is unique.
“I’m not the only one in this space, but we expect our approach to change the way people think about engineering sensor-actuator devices,” she said. “Currently, these devices are mainly based on cell surface sensing capabilities mostly achieved by rewiring native ligand-receptor interactions or evolving new cell surface receptors. These are linked to signal transduction systems that allow cells to translate the extracellular stimulus into a detectable output or therapeutic program.”
Segatori’s synthetic biological circuits are engineered to function inside cells and quickly respond to changes in gene activity.
“We want to develop a novel class of cellular sensors,” she said. “These would actuate the desired biomolecular program in response to the detection of the device’s physiological state, achieved through real-time monitoring of the activity of chromosomal genes.
“For instance, we can imagine developing cellular devices that activate a therapeutic response upon detection of transcriptional signatures associated with the detection of markers of a tumor microenvironment.”
Segatori, an associate professor of bioengineering, chemical and biomolecular engineering, and biosciences, said the circuit’s ability to rapidly turn itself off once the stimulus disappears is key. “Current engineered cells typically lack control over the response time and dynamics,” she said. “Drug dosage becomes an issue.
“But if we can make smart cells that sense the need of your body for therapeutics and just adjust drug release accordingly, that would be really useful for many applications.”