New ROOT method charts a path to reversing biological changes once thought irreversible

A KAIST research team has developed a new method called ROOT, which can potentially reverse irreversible biological changes in cells. This breakthrough could have significant implications for treating diseases like cancer and aging, where cells become locked in abnormal states. In many cases, once a cell changes its state, it cannot return to its original condition even after the external stimulus that caused the change is removed.

This "irreversibility" is crucial for normal biological processes such as cell differentiation, but it can also contribute to disease progression. The researchers identified the causal circuits responsible for irreversibility in intracellular molecular networks and created a control technology called ROOT. ROOT represents these complex processes as computational logic models and analyzes them using systems biology techniques.

By doing so, it allows scientists to pinpoint the core circuits that cause irreversibility, known as the "irreversibility kernel." Beyond identifying these circuits, ROOT also proposes two innovative control strategies. The first, called "resetting control," restores a cell to its pre-change state while preserving the cell's underlying irreversible property.

The second, "reversing control," eliminates the source of irreversibility itself, allowing the cell to transition freely between different states. The researchers tested the ROOT method on various biological models, including B-cell differentiation, epithelial-mesenchymal transition in lung cancer, and enterocyte and beta-cell differentiation models.

In all these cases, ROOT accurately identified causal circuits that matched known cell-fate determinants. The team believes that ROOT could be used to develop new treatment strategies that restore abnormally fixed cell states back to normal, moving beyond simply removing cells that have become fixed in an abnormal state.