lipflip – Bioengineers at Rice University have achieved a significant breakthrough in synthetic biology. Unveiling a cutting-edge construction kit for creating custom sense-and-respond circuits in human cells. Published in Science, this innovative research opens new possibilities for treating complex conditions like autoimmune diseases and cancer.
Xiaoyu Yang, a graduate student in Rice’s Systems, Synthetic, and Physical Biology Ph.D. program. Emphasized the transformative potential of the study. “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. This work brings us closer to building ‘smart cells’ capable of detecting disease and releasing tailored treatments immediately.”
The technology leverages phosphorylation, a natural cellular process that adds a phosphate group to a protein. This mechanism allows cells to convert external signals into intracellular responses, such as moving, secreting substances, or expressing genes. By tapping into phosphorylation, researchers can design artificial circuits that mimic or enhance these cellular responses.
Rice Scientists Unlock New Potential in Smart Cell Design
Rice University researchers have unlocked a major breakthrough in “smart cell” engineering by reimagining how phosphorylation-based signaling can be harnessed for therapeutic purposes. Phosphorylation, a natural cellular process involving the addition of phosphate groups to proteins. Often triggers cascading signals in multicellular organisms, much like falling dominoes. Historically, attempts to repurpose this process for medical applications in human cells relied on modifying existing signaling pathways. But their complexity has limited progress.
Rice scientists have now taken a bold new approach. Instead of working within the constraints of native pathways, the research team treated each phosphorylation cycle as a standalone unit. By linking these units together in novel ways. They created entirely new pathways that connect cellular inputs (such as detecting a pathogen or tumor marker) to outputs (like triggering a therapeutic response).
“This dramatically expands the design space for signaling circuits,” explained Caleb Bashor, assistant professor of bioengineering and biosciences and the study’s corresponding author. “We discovered that phosphorylation cycles are not only interconnected but also interconnectable, allowing for the construction of highly sophisticated, custom signaling pathways.”
Advances Smart Cell Engineering with Synthetic Phosphorylation Circuits
Rice University bioengineers have achieved a significant breakthrough in smart cell design by creating synthetic phosphorylation circuit. Highly tunable and capable of functioning alongside natural cellular processes without hindering cell viability or growth. This modular, do-it-yourself approach allows for the design of circuits that can sense and respond to environmental inputs. Amplifying weak signals into significant outputs.
“Our synthetic signaling circuits, made entirely of engineered protein parts, matched the speed and efficiency of natural human cell pathways,” said Xiaoyu Yang, lead author and graduate student. “This outcome was unexpected but rewarding, reflecting the extensive effort and collaboration that made it possible.”
Developing these circuits required determining the intricate rules for designing, connecting, and tuning both intra- and extracellular outputs. The circuits also replicate the system-level amplification capabilities of native phosphorylation cascades. Experimental observations confirmed the accuracy of the team’s quantitative models. Showcasing the framework’s potential as a foundational tool for synthetic biology.
One of the most distinct advantages of these synthetic circuits lies in their rapid response time. Phosphorylation occurs within seconds or minutes, enabling the circuits to react swiftly to physiological events. This marks a major improvement over previous designs based on processes like transcription, which can take hours to activate.
Develop Synthetic Cell Circuits to Combat Autoimmune and Immunotherapy Challenges
Rice University bioengineers have successfully developed synthetic cellular circuits capable of detecting inflammatory signals. Demonstrating potential for applications like managing autoimmune flare-ups and reducing immunotherapy-associated toxicity. These groundbreaking circuits respond quickly and accurately to external signals, showcasing a significant advancement in the field of synthetic biology.
“Our research demonstrates the feasibility of building programmable circuits in human cells that can rapidly and precisely react to signals,” said Caleb Bashor, assistant professor and deputy director of the Rice Synthetic Biology Institute. This study represents the first-ever framework for constructing synthetic phosphorylation circuits, a system designed to emulate and enhance the rapid response capabilities of natural cellular processes.
The team validated the circuits by testing their sensitivity to external factors, such as inflammatory markers, and successfully engineered a circuit that could detect these signals. This breakthrough opens the door for real-time therapeutic interventions tailored to dynamic physiological conditions.
Caroline Ajo-Franklin, director of the Rice Synthetic Biology Institute, emphasized the transformative nature of this research. “If the past two decades of synthetic biology have focused on gradually manipulating bacterial responses to environmental cues, this work from the Bashor lab propels us into a new era: controlling mammalian cells’ immediate responses to change,” said Ajo-Franklin, a professor and Cancer Prevention and Research Institute of Texas Scholar.
Launched earlier this year, the Rice Synthetic Biology Institute aims to leverage the university’s deep expertise in this field and foster collaborative research. The team’s findings underscore the institute’s mission by providing a robust foundation for future innovations in cellular engineering, potentially revolutionizing therapeutic approaches for complex diseases.