Data-driven mathematical model of light- and melatonin-mediated effects on the human circadian clock

Abstract: The pineal secretion of the hormone melatonin demonstrates a circadian (~24 h) rhythm with the onset of melatonin production at night and offset each morning under tight circadian control. Melatonin exerts both acute sleep-promoting effects and chronobiotic effects on the circadian clock, and exogenous melatonin supplements are increasingly being used as a treatment for a variety of sleep and circadian diseases and disorders. Phase shifting of the circadian clock can also be accomplished through ocular exposure to light. However, the interacting effects of light and melatonin on the circadian clock are not well understood. To analyze the dynamic behavior of both endogenous and exogenous melatonin’s influence on the circadian clock, we extend a previously published mathematical model of the circadian clock to account for melatonin forcing and integrate it with a model of melatonin dynamics that describes both endogenous melatonin produced by the pineal gland and exogenous melatonin entering the system through ingested oral supplements. This modeling framework allows for the study of melatonin’s dynamic properties and interaction with the circadian clock and provides insight into optimal light exposure and exogenous melatonin administration schedules to induce desired phase shifting of the circadian clock.

Bio: Cecilia Diniz Behn is an associate professor in the Department of Applied Mathematics and Statistics at Colorado School of Mines, and an adjoint assistant professor in the Department of Paediatrics at the University of Colorado School of Medicine. She previously completed graduate training in the Department of Mathematics and the Center for BioDynamics at Boston University; and postdoctoral training in the Division of Sleep Medicine at Harvard Medical School and the Department of Mathematics at the University of Michigan. Her research applies multiscale mathematical modeling to investigate key questions in metabolism, sleep, and circadian rhythms. Specifically, she models key dynamics in whole-body metabolism, including changes in glucose, glycerol, and insulin; sleep and circadian (~24 h) neurophysiology; and the diverse interactions among these systems. Dysregulation of metabolism and/or sleep has dramatic implications for human health, and the complex ways in which these systems interact, both on a mechanistic and behavioral level, are just beginning to be understood.

Lab's webpage: https://people.mines.edu/cdinizbe/

Access to the meeting: Zoom Link