No matter how developed medical treatments get, it is difficult to administer the right dosage of a certain medicine or therapy required to cure a particular ailment. This is known as the “Goldilocks” problem because finding the precise quantity and moment to administer a drug is always a difficult challenge. 

Bioengineers from the University of Washington and the University of California at San Francisco have developed a solution to this problem. An artificial protein that mimics an integrated computer circuit called Latching Orthogonal Cage-Key pRotein [LOCKR]. This incorporates the idea of smart cells that behaves like tiny autonomous robots, that may be used to detect diseases and damaged cells. 

The structure of the protein is shaped like a barrel and once opened has a molecular arm that can be engineered to control virtually any cell process. The paper states that it could degrade specific proteins, initiate a cell self-destruct process and direct molecular traffic. 

LOCKR has two states, its arm remains hidden [background] until the barrel structure [grey] is opened [foreground] and requires a key [black] to open it. This reveals a bioactive peptide [yellow] that can interact with other molecules in the cell. It works as a switch mechanism and remains dormant when closed and is activated only when the structure is open. 

The ability to control this switch mechanism on such a molecular scale can be seen as a parallel to integrated circuits [IC] that powers modern-day computers. This acts as a biological equivalent of the IC’s inside cells. 

Hana El-Samad, PhD, LOCKR’s co-inventor said,

“In the same way that integrated circuits enabled the explosion of the computer chip industry, these versatile and dynamic biological switches could soon unlock precise control over the behavior of living cells and, ultimately, our health.”

In the second paper, the researchers demonstrated the technology’s circuit building potential. They constructed circuits that were able to dynamically regulate cellular activity in response to cues from the cell’s internal and external environment. The protein can be degraded by switching the protein of interest on by using a tool called degronLOCKR. 

When the circuits, which included a genetically encoded sensor, detected a disruption of normal cell activity, degronLOCKR responded by destroying the proteins that direct the cellular “software” that caused the disruption, until the cell returned to normal – a process similar to how thermostats continually sense ambient temperature and direct HVAC systems to shut off or turn on to maintain a desired temperature.

Andrew Ng, PhD, a co-first author said 

“LOCKR, and more specifically, degronLOCKR, opens a whole new realm of possibility for programming cells to treat a wide range of debilitating conditions for which safe and effective treatments are not yet available,”

This could potentially be used to treat ailments like traumatic brain injury [TBI] which exemplifies the “Goldilocks” problem that we spoke about. When the brain incurs a traumatic injury, it responds by initiating an unrestrained inflammatory process that is necessary for its healing process. However, it usually exceeds the required amount and could end up permanently damaging the brain, which is a prime reason why people fall into a coma due to this vigorous inflammation process.

With the help of degronLOCKR, we will be able to transform normal cells into smart cells by installing this ‘bio-circuit’ to monitor this inflammation. This will help in properly administering the right amount of drugs or initiate a cell degeneration process in a moderate way, so they don’t over/under do the therapeutic process. 

It won’t stop there since we can use these smart cells to potentially cure terminal illnesses like cancer, to monitor the unpredictable cell growth and even autoimmune diseases. This opens the possibility of building such smart cells in order to monitor or regulate certain chemical processes that take place in our body. With the help of smart cells, implants required to monitor certain aspects of your health could be a thing of the past.

This is a good example of how an electronic process can be mimicked in order to alleviate or solve biological problems. Since it’s usually the other way around, where people use bio-inspired algorithms for building algorithms and artificial neural networks [ANN]. 

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