Multiscale modeling in the framework of biological systems and its potential for spaceflight biology studies

A central tenet of systems biology is that biological systems are greater than the sum of their component parts. Spaceflight is associated with hazards including radiation exposure and microgravity which impact different echelons of biological organizations spanning molecular, cellular, organ, and organismal levels. These insults lead to physical damage, including muscle and bone loss, neurological damage, and impaired immunity. Mitochondrial dysfunction and biological alterations occurring during spaceflight have been reported. The health challenges presented by long-term space travel must be addressed and appropriate countermeasures developed to protect astronauts. Increasing quantity of multiomics data are being generated from cells and model organisms flown in space, with physiological data from astronauts. Systems biology approaches leveraging mathematical reasoning and computational modeling are required to characterize these components in a holistic fashion. In this review, we provide an historic perspective on multiscale biological systems modeling, followed by a discussion on its utility for spaceflight biology research.