Rapid Response Synthetic Biology Systems Engineered for Near-Instantaneous Functionality
In a groundbreaking study, a team of synthetic biologists at MIT, led by Deepak Mishra, have developed an alternative approach to designing cell circuits that relies on fast, reversible protein-protein interactions. The research, which was funded by various organizations including the Siebel Scholars Award, Eni-MIT Energy Research Fellowship, National Science Foundation Graduate Research Fellowship Program, Institute for Collaborative Biotechnologies, SynBERC grant from the National Science Foundation, and the Center for Integrated Synthetic Biology through the National Institutes of Health, was published in the prestigious journal Science.
The study, which also includes authors such as Ron Weiss, Tristan Bepler, Bonnie Berger, Brian Teague, and Jim Broach, introduces a toggle network that is larger and more complex than most previously designed synthetic circuits. This network, the first synthetic circuit to consist solely of phosphorylation / dephosphorylation protein-protein interactions, is designed as a toggle switch that can quickly and reversibly switch between two stable states.
The researchers used yeast cells to host their circuit and created a network of 14 proteins from various species to regulate each other in response to a particular event. The target of this circuit is sorbitol, a sugar alcohol found in many fruits. When the cell is exposed to sorbitol, the circuit stores a memory of this exposure in the form of a fluorescent protein localized in the nucleus.
One of the key advantages of this new approach is that it allows circuits to be turned on much faster, within seconds, compared to traditional methods that require waiting for genes to be transcribed and translated. This speed could be crucial in applications such as detecting environmental pollutants or creating diagnostics that reveal disease states or imminent events such as a heart attack.
The researchers envision designing circuits that could be programmed into human cells to report drug overdoses or an imminent heart attack. Another potential application is deploying custom protein networks within mammalian cells as diagnostic sensors for abnormal hormone or blood sugar levels. The circuit can also be reset by exposing it to a different molecule, in this case, isopentenyl adenine.
Moreover, the memory is also passed on to future cell generations. The network can also be programmed to perform other functions in response to an input, such as shutting down cells' ability to divide after sorbitol is detected.
This new approach could also be useful for creating environmental sensors or diagnostics that could reveal disease states or imminent events such as a heart attack. Inside living cells, protein-protein interactions are essential steps in many signaling pathways, including those involved in immune cell activation and responses to hormones or other signals.
The search results do not contain information on who developed the new method for creating protein-based circuits based exclusively on fast, reversible protein-protein interactions that enable signaling within seconds. However, this groundbreaking research by MIT's synthetic biologists opens up exciting possibilities for the future of synthetic biology and cellular signaling.
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