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Bioengineers at Rice University have made a significant advancement in the field of synthetic biology by devising a method that enables the creation of specialized sense-and-respond mechanisms within human cells. This significant milestone, described in a recent edition of the renowned journal Science, opens up possibilities for transforming the management of intricate illnesses such as cancers and autoimmune diseases through the creation of engineered “smart cells” that can detect and treat diseases in real-time.
Advances in “Smart Cells”: A Quantum Leap in Disease Management
Xiaoyu Yang, a doctoral candidate in the Systems, Synthetic and Physical Biology program at Rice University, envisions a world where cells are equipped with minuscule protein-based decision-making systems. “Our findings greatly advance our capability to engineer ‘smart cells’ that have the potential to recognize disease indicators and instantaneously initiate tailored therapeutic actions,” Yang remarked.
The innovative method developed by Yang and the Rice University team capitalizes on phosphorylation—a natural cellular process by which proteins have phosphate groups attached. This mechanism is essential for a vast array of cellular operations such as movement, secretion, immune responses, and gene regulation. The researchers conceptualized utilizing each step in the phosphorylation process as a basic building block for crafting new pathways linking cellular inputs and outputs.
Assistant Professor Caleb Bashor, who is a member of the bioengineering and biosciences departments at Rice and the paper’s principal author, underscored the significance of their discovery. “We learned that phosphorylation cycles could be intricately interconnected—a possibility that was uncertain at this complexity level in previous research,” Bashor explained. He highlighted that their strategy enables the design of customized phosphorylation circuits that can operate in conjunction with natural cellular pathways, without compromising cell health or proliferation.
Contrary to initial skepticism, the team’s in-vivo experiments revealed that the manufactured circuits, which are composed entirely of custom-engineered protein components, function with a level of speed and precision akin to the natural signaling mechanisms found in human cells. The approach illustrated by the Rice research group also presents a systems-level benefit, effectively intensifying weak input signals into pronounced outputs, aligning with their quantitative models.
The circuits put together by the research team demonstrated prompt responsiveness to physiological signals, reacting in seconds to minutes. In tests, the circuits proved sensitive to external stimuli like inflammatory agents. The pioneering work resulted in a cellular circuit that can potentially identify and react to autoimmune exacerbations while lessening the toxicity typically associated with immunotherapy treatments.
Caroline Ajo-Franklin, head of the Rice Synthetic Biology Institute, praised the team for their groundbreaking contribution to the synthetic biology field. “In the past two decades, synthetic biologists have primarily focused on controlling the gradual responses of bacteria to environmental cues. However, the Bashor lab’s work propels us into an exciting new realm—regulating the immediate responses of mammalian cells to changes,” Ajo-Franklin declared.
The research was funded by several agencies, including the National Institutes of Health, the Office of Naval Research, a variety of foundations, and the National Science Foundation.
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