First-in-class RNA sensors for studying myelin dynamics and disease

The central nervous system (CNS) relies on complex processes for proper function. Such processes malfunction in disease, aging, and injury, and there is great need for therapies to restore proper function. Computers are complex machines; they can receive input from the user, compute the proper response, and create an output accordingly. Synthetic biologists attempt to emulate this in a therapeutic context, yet instead of coding in ones and zeroes, they code in ATGC, the programming language of cells that encodes all proteins in the body. In this project, we integrate novel RNA sensors in “smart” circuits in oligodendrocytes, non-neuronal cells required for proper brain function and learning. In demyelinating disease, such as Alzheimer’s disease, their regrowth and survival are crucial. We build two circuits; the first analyzes the cell environment to “sense” when these cells are at the best stage for regrowth and activate a growth program to promote their survival. The second circuit senses the formation of the disease-associated state, allowing us to understand and reverse their contribution to disease. A successful outcome will shed light on the function of oligodendrocytes in remyelination and disease and enable the development of these tools for other complex challenges in the CNS.