Animals are complex systems operating at multiple spatial and temporal scales, facing the challenge of how to change in appropriate ways, degrees, and times, in response to the diverse internal and external influences to which they are exposed. Discovering the system-level attributes of organisms that make them resilient or robust-or sensitive or fragile-to change presents a grand challenge for biology. Knowledge of these attributes and the underlying mechanisms controlling them is crucially needed to predict how organisms will respond to short-and long-term changes in internal and external environments, including those driven by climate change. Organismal biologists require novel approaches that extend beyond traditional disciplinary boundaries, especially when they partner with mathematicians and engineers. Pursuing this research enterprise will not only give us a deeper understanding of how organisms will face future challenges, but it will also reveal nature-inspired solutions in complex engineered systems, both of which will benefit science and society.Keywords: organismal biology, grand challenges, integrative biology, systems engineering, predictive modeling Animals are inherently complex and are composed of multiple interconnected elements. They and their component elements must have the capacity to maintain stability and to simultaneously change in response to internal and external stimuli. For example, young animals must be able to process neurosensory inputs as they move through the environment while their brains and nervous systems continue to develop. As they grow and develop, structures used for locomotion may simultaneously change in their function and control because of changes in size and morphology (Hale 2014). Those same animals must maintain the internal physiological function of all of their systems throughout ontogeny and as they experience shifting internal 1 Dianna K. Padilla (padilla@stonybrook.edu) is a professor in the Department of Ecology and Evolution at Stony Brook University, in Stony Brook, New York. Thomas L. Daniel is a professor, in the Department of Biology, Billie J. Swalla is the director of and a professor in the the Friday Harbor Laboratories and in the Department of Biology, and Daniel Grünbaum is an associate professor in the School of Oceanography at the University of Washington, in Seattle. Patsy Dickinson is a professor in the Department of Biology and in the Neuroscience Program at Bowdoin College, in Brunswick, Maine. Cheryl Hayashi is a professor in the Department of Biology at the University of California, Riverside. Donal T. Manahan is a professor in the Department of Biological Sciences at the University of Southern California, in Los Angeles. James H. Marden is a professor in the Department of Biology at Pennsylvania State University, in State College. Brian Tsukimura is a professor in the Department of Biology at California State University, Fresno. 2 and external environments. In addition, animals and animal systems exhibit many nonlinear and time-dependent ...