A human space flight is inherently complex. A successful mission involves the proper interaction of the “system-of-systems” of individual physiology and psychology, crew teamwork, vehicle and habitat design and function, ground-control communications, mission rules and goals, and many other factors. Research is needed to address these interdependencies. We approach this widespread integration in two ways. First, through a NASA project (https://www.nasa.gov/mission/cipher/) that will acquire biomedical data from a variety of body systems on several ISS missions; these data will be examined for correlations and synergies (Shelhamer is PI on this task). Second, through a larger modeling effort (in the planning stages) that will combine these disparate factors in the form of a network, to which mathematical tools related to system resilience can be applied. These efforts can draw on the large body of cross-disciplinary knowledge available in the different divisions of Johns Hopkins.