Grant: Project Grant

Neurological and mental health disorders are one of the leading causes of disabilities threatening global health. Currently affecting 15% of the population worldwide and 10% of Canadians, the number of patients with neuropsychiatric conditions is expected to double in the next two decades. The expansion of the aging population, social inequalities, and current challenges of modern society are some of the many factors contributing to the envisioned increase of health care expenditure. Natural products are a huge resource of medicines inspiring more than 70% of drugs currently in clinical use. Recent studies have shown that psychedelics are promising pharmaceutical targets for various neurological, mental and mood disorders. Still, only few compounds have been extensively researched due the limited amounts available. In this project, we will apply an interdisciplinary approach to discover novel psychedelics for neurological and mental health disorders. Using AI tools, we will identify the chemical structure of novel molecules that are either not yet found or not produced in nature and predict their bioactivities against human GPCR receptors. We will reconstruct the AI- designed pathways in an engineered microbial chassis, such as baker's yeast. This strategy will allow sustainable production of promising candidates through precision fermentation resulting in enough amounts of compounds of interest for further studies. Finally, we will validate the biological activities of drug lead candidates through in vitro and in vivo measures of cellular signaling, to show how the compounds modulate GPCR function. Key compounds will then be tested for analgesic, mood-altering or addiction-suppressing effects, depending on their pharmacological properties. This project will generate new pharmaceuticals for anxiety, depression, or post-traumatic stress disorder, to address the economic and personal burdens these disorders represent.