A non-invasive, fast on/off “Odourgenetic” Method to Manipulate Physiology

Summary Manipulating molecular processes governing physiological functions has significant potential for clinical therapeutics and is an important approach to elucidate the cellular basis of physiological functions. Here, we designed a Odourgenetic system co-expressed Drosophila odorant receptor system (DORs) consisting of OR35a and OR83b, which were exclusively activated by their odor ligand, 2-pentanone. Applying 2-pentanone to DOR-expressing cells or tissues induced calcium influx and membrane depolarization. By inhalation of 2-pentanone, we successfully applied DORs to manipulate behaviour, control insulin secretion and regulate blood glucose and manipulate muscle contraction and associated limb movement. Because 2-pentanone rapidly enters the blood upon inhalation and leaves the body by exhalation, this odorant can be used with DORs to manipulate cellular function, and the manipulation can be terminated at any time. Such feature approach significantly improves the safety and controllability of DORs used in the clinic. Thus, the present study developed a non-invasive, controllable, fast on/off method to manipulate cellular activity and behaviour on a time scale of minutes.