Myelin sheaths are composed of spirally wrapped glial cell plasma membrane tightly compacted by a family of myelin-associated proteins that protect and insolate axonal fibers in neurons. They increase the transverse resistance of each fibre and lead to voltage-gated channel clustering at nodes of Ranvier supporting node-to-node saltatory conduction, which vastly accelerates conduction rates and limits repolarization energy requirements to the nodal domain. Each oligodendrocyte (OG) can unsheathe multiple fibers; the ability to do so is regulated by both calcium (Ca2+) signaling in these cells5 and by axonal activity6,7, allowing myelin to be adaptive. A rapidly growing evidence suggests that such plasticity plays a key role in both normal and abnormal nervous system function. This highlights that axon-myelin-OG relationships define a complex multivariable system in which large functional consequences would result from each variable. How these combine to elicit an integrated structural response to physiological stimuli in the nervous system during health and disease is poorly understood and have benefited enormously from an in-depth computational analysis. In this talk, I will provide an overview of our recent work modeling this system by focusing on only two aspects: myelin-sheath plasticity in vivo and calcium signaling in OG.

Bio: Dr. Khadra is an Associate Professor in the Department of Physiology, McGill University and Co-Director of the Centre for Applied Mathematics in Medicine & Bioscience (CAMBAM). The focus of his research program is to understand the interactions and mechanisms underlying the behaviour of various physiological systems using mathematical and computational approaches. He and his group use these approaches to (i) provide important insights into the cellular and molecular processes regulating these systems; (ii) test experimental hypotheses; (iii) identify targets to manipulate their dynamics; (iv) determine the causes of abnormalities exhibited by them; and (v) ultimately develop technological tools to decipher their kinetics. The mathematical models that emerge from these studies raise intriguing mathematical questions that are then analyzed either numerically, using computational tools, or theoretically, using methods of nonlinear and stochastic dynamics. This work is conducted in close collaboration with several renowned national and international experimental laboratories.