In an advance that could change how we treat complex diseases, bioengineers at Rice University have developed what amounts to a biological construction kit for programming human cells to detect and respond to specific disease markers. The research, published in Science, represents a fundamental shift in synthetic biology by enabling rapid cellular responses to disease signals.
The innovation centers on phosphorylation – a natural process that cells use to respond to their environment. While this process has been known to scientists for years, the Rice team has found a way to harness it for creating customizable cellular circuits that can detect and respond to specific disease markers in seconds or minutes, rather than the hours required by previous approaches.
“Imagine tiny processors inside cells made of proteins that can ‘decide’ how to respond to specific signals like inflammation, tumor growth markers or blood sugar levels,” said Xiaoyu Yang, lead author and graduate student in Rice’s Systems, Synthetic and Physical Biology Ph.D. program. “This work brings us a whole lot closer to being able to build ‘smart cells’ that can detect signs of disease and immediately release customizable treatments in response.”
The breakthrough came from a shift in perspective about how cellular signaling works. The research team discovered that the individual steps in cellular signaling could be treated as modular units – much like building blocks – that could be reassembled in new ways to create entirely novel pathways linking cellular inputs and outputs.
Dr. Caleb Bashor, assistant professor of bioengineering and biosciences at Rice and the study’s corresponding author, emphasized the significance of this modular approach: “This opens up the signaling circuit design space dramatically. It turns out, phosphorylation cycles are not just interconnected but interconnectable – this is something that we were not sure could be done with this level of sophistication before.”
The team has already demonstrated practical applications, engineering a cellular circuit that can detect inflammatory factors – a development that could lead to new treatments for autoimmune conditions and reduce toxicity in immunotherapy. The synthetic circuits performed with similar speed and efficiency as natural signaling pathways, a result that surprised even the researchers.
Caroline Ajo-Franklin, director of the recently launched Rice Synthetic Biology Institute, placed the work in broader context: “If in the last 20 years synthetic biologists have learned how to manipulate the way bacteria gradually respond to environmental cues, the Bashor lab’s work vaults us forward to a new frontier – controlling mammalian cells’ immediate response to change.”
The research, supported by multiple organizations including the National Institutes of Health and the Office of Naval Research, represents a significant step toward developing more effective and precise cellular therapies for conditions ranging from autoimmune diseases to cancer. With this new ‘construction kit,’ researchers can now build cellular circuits that respond to disease markers in real-time, potentially leading to more targeted and efficient treatments.