New gene activity sensors, activators could help treat diabetes, cancer, and other disorders

People likely have apps on their cellphone. A new study at Rice University provides the viability of apps for actual cells.

Laura Segatori. Image Credit: Rice University.

Laura Segatori, a bioengineer at Rice University, and her Brown School of Engineering team were awarded a prestigious National Institutes of Health Research Project Grant to create gene activity sensors and activators that, according to her, hold unmatched potential for the treatment of infectious diseases, diabetes, genetic disorders, and cancer.

The four-year, $1.8 million grant is awarded by the National Institute of Biomedical Imaging and Bioengineering. This is followed by a smaller National Science Foundation grant in January proposing that the Segatori lab’s approach for engineering cellular devices can be applied to almost any cellular process related to a transcriptional response.

The concept is to program mammalian cells to recognize their environment and create living designer systems that identify and correct human pathologies. The concept is not something new, but Segatori’s strategy, developed based on a novel system proposed last year to enhance the 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,” stated Segatori.

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.”

Laura Segatori, Bioengineer, Rice University

The synthetic biological circuits developed by Segatori have been designed to work within cells and respond fast to changes in gene activity.

“We want to develop a novel class of cellular sensors. 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,” added Segatori.

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.”

Laura Segatori, Bioengineer, Rice University

According to Segatori, an associate professor of bioengineering, chemical and biomolecular engineering, and biosciences, the potential of the circuit to quickly turn itself off as soon as the stimulus fades is then highlight. “Current engineered cells typically lack control over the response time and dynamics,” she noted. “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.”

Laura Segatori, Bioengineer, Rice University