Engineering biosensors for drug profiling across systems

The overall aim of this proposal is to elucidate the causal link between norepinephrine (NE) and serotonin (5-HT) dynamics in major depressive disorder (MDD) and to establish new drugs for its treatment. To this end, we have decided to bring together experts in their respective fields: Olivia Masseck (expert in 5-HT and in vivo models of depression), Tommaso Patriarchi (pioneer in the development of DA and NE biosensors) and Harald Sitte (pharmacologist, expert in drug characterisation and new psychoactive substances). To this end, we will develop new, improved, high-affinity variants of NE sensors. Based on these new NE sensors and established 5-HT sensors (sDarken), an in vitro screening of new psychoactive substances for their potential as antidepressants will be performed. In parallel, we will use these biosensors to identify signatures of resilience in a mouse model of depression. In the final phase of the project, newly identified compounds will be evaluated for their antidepressant potential.