Biotechnology (Commonwealth Union) – The specific role of cellular organelles has had greater scrutiny by a wide variety of researchers in recent years. The ability to correct specific functions of distressed cells as a therapeutic model has also been explored.
A cell that has become permanently locked into an abnormal condition — as seen in cancer cells — may not be beyond repair. Scientists who are located in South Korea at the Korea Advanced Institute of Science & Technology (KAIST) have discovered the “molecular lock” that is responsible for keeping cells in these altered states, showing us a possible way to shatter the lock and restore cells to their biological form in its originality.
KAIST (President Choongsik Bae) made public this month that researchers led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering has, for the first time, found that the causal circuits behind irreversible changes in intracellular molecular networks. The researchers also developed a breakthrough control technology, called ROOT, which can manipulate these circuits and help return altered biological states to their initial state.
Cells in the human body continuously adjust their condition in response to signals from their surroundings. However, these changes are often permanent, meaning cells may fail to return to their previous state even after the triggering signal is removed.
This irreversible behavior plays a crucial role in healthy biological functions, such as allowing cells to specialize into specific types with distinct roles. However, the same mechanism can contribute to disease development. One example is epithelial–mesenchymal transition, a process that enables cancer cells to move, spread, and invade nearby tissues.
Complicating the issue further, the mechanisms that allow cells to maintain these altered states are incredibly complex. The regulatory network contains more than a thousand positive feedback loops, where one molecule triggers a chain reaction of other molecules that eventually reactivate the original molecule. This resembles the piercing feedback noise created when a microphone is positioned too close to a speaker, causing sound to continuously amplify itself. As a result, a cellular change triggered by an outside signal can continue even after the original trigger disappears, because the cell’s internal molecules continue to reinforce each other. Until now, identifying which of these many feedback circuits actually drives a cell into a permanent state has remained a major challenge.
To address this challenge, the researchers created ROOT technology, an abbreviation for Revelation of the Original circuit of irreversible Transition. The system converts intracellular regulatory networks into computational logic models and examines them using systems biology approaches. With ROOT, the team was able to simulate how cells preserve signals even after external stimulation is removed, enabling them to pinpoint the essential circuits responsible for irreversible changes. They referred to this critical group of circuits as the “irreversibility kernel.”
After uncovering the underlying mechanism, the researchers introduced two innovative approaches for controlling these cellular states.
The first approach, called “resetting control,” brings a cell back to its original condition before the transformation while keeping its irreversible characteristics unchanged. In other words, it is like opening a locked door and returning inside without removing or altering the lock itself.
Beyond identifying the specific underlying cause, the team also developed two innovative control strategies.
The first approach, known as “resetting control,” returns a cell to the state it occupied before the change, while preserving the underlying irreversible mechanism. It is similar to keeping the lock intact but unlocking the door and restoring it to its original position.
The second approach, called “reversing control,” eliminates the mechanism responsible for making the change irreversible in the first place. This enables the cell to transition freely between different states. In other words, it is like disabling an automatic door-locking system so the door can be opened and closed repeatedly without locking itself.
