Developing new molecular tools for the mapping and manipulation of neuronal circuits

The brain’s electrical chatter during learning, sleep, or memory recall remains largely invisible to current molecular tools. This project aims to build a new set of protein-based sensors and switches that can record which neurons fire during specific behaviours, and then write that firing history directly into the cell’s DNA. Today, neuroscientists can watch brain activity with calcium imaging or manipulate it with optogenetics, but they cannot easily link a precise pattern of neural firing to a stored memory or a learned task. The gap is technological: no existing molecular system can both detect and permanently log neuronal activity at single-cell resolution across a whole circuit. The researchers are developing three tools: calcium-activated light-producing enzymes (luciferases), light- and activity-driven transcription factors built from engineered proteases and photocontrollable proteins, and a calcium-activated CRISPR-Cas9 system. Each tool couples a neuron’s firing to a genetic readout, effectively encrypting its activity history into DNA. If successful, these tools would let scientists map the neural circuits underlying specific behaviours—such as memory retrieval or sleep regulation—with unprecedented precision. This is fundamental science. There is no immediate clinical or commercial application. But similar fundamental work on light-sensitive proteins and CRISPR has already transformed neuroscience and gene editing, respectively. A deeper understanding of how the brain encodes and stores information could eventually inform treatments for memory disorders or brain injury.