Rapid-response synthesized biological systems in action
In a groundbreaking discovery, synthetic biologists at MIT, Harvard University, the University of Wisconsin, and Penn State Hershey Medical Center have developed an innovative approach to designing cell circuits that rely on fast, reversible protein interactions. This new method could pave the way for the creation of environmental sensors, diagnostics, and even personal health monitors.
The study, which appears in the prestigious journal Science, reveals the development of protein-based circuits that can respond quickly within seconds. This rapid response time is a significant improvement over traditional methods that involve gene transcription and translation, which can take much longer.
The protein-based circuits, when hosted in yeast cells, form a network of 14 proteins from various species. The network, the first synthetic circuit to consist solely of phosphorylation / dephosphorylation protein-protein interactions, is designed as a toggle switch that can switch between two stable states.
One of the key features of these protein-based circuits is their ability to 'remember' specific events such as exposure to certain chemicals. For instance, the circuit can remember exposure to sorbitol, a type of sugar alcohol. This memory is stored in the form of a fluorescent protein localized in the nucleus and can be passed on to future cell generations.
Moreover, these protein networks can be programmed to perform other functions in response to an input. A demonstration of this functionality is a circuit that shuts down cells' ability to divide after sorbitol is detected.
The potential applications of these protein networks are vast. They could be useful for creating environmental sensors or diagnostics that reveal disease states or imminent events such as a heart attack. A potential application within mammalian cells is as diagnostic sensors to detect abnormal hormone or blood sugar levels.
In the longer term, the researchers envision designing circuits that could be programmed into human cells to report drug overdoses or an imminent heart attack. This could revolutionize healthcare by enabling early detection and intervention of various health conditions.
The research was funded by several grants, including the Siebel Scholars Award, an Eni-MIT Energy Research Fellowship, the National Science Foundation Graduate Research Fellowship Program, the Institute for Collaborative Biotechnologies through the U.S. Army Research Office, a SynBERC grant from the National Science Foundation, and the Center for Integrated Synthetic Biology through the National Institutes of Health.
The circuit can also be reset by exposing it to a different molecule, in this case, isopentenyl adenine. This reset feature is crucial for the circuit's functionality and adaptability.
The researchers at Harvard University have also developed similar protein-based circuits that could be used for detecting environmental pollutants or disease states. These findings mark a significant step forward in the field of synthetic biology and its potential applications in healthcare and environmental monitoring.
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