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

One of the biggest challenges of this century is to understand how the brain computes, transmits and stores information at single-cell resolution. Which neurons are active when a certain task is learned or at different stages of an organism's development? Is it possible to manipulate neurons to retrieve a particular memory? The lack of molecular technology currently hinders our understanding of the complex processes by which our brain moves from simple signals to complex tasks such as sleep or memory formation.

The main goals of this research proposal are to visualise, map and manipulate the active neural circuits underlying specific behaviours and to encrypt into DNA the neuronal firing history. These fundamental questions will be addressed through the development of: Ca2+-activated luciferases, light- and activity-driven transcription factors (engineered by artificial proteases and photocontractable proteins) coupled to transcriptional readout, and Ca2+-activated CRISPR-Cas9 systems. These new molecular tools are being developed through a synergy between synthetic chemistry and powerful synthetic biology techniques such as directed evolution to optimise the performance of the different systems.