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Projects in the life sciences continue to increase in complexity as they scale to answer deeper and more diverse questions. They employ technologies that generate increasingly large ‘omic’datasets and research teams regularly include experts ranging from animal care technicians, veterinarians, human health clinicians, geneticists, immunologists, and biochemists to computer scientists, mathematical modelers, and data scientists, often located at different institutions. Providing the cyberinfrastructure support framework (IT, data management, communication, documentation, and aspects of project management related to these areas) for these projects requires a diverse set of technical tools and soft skills. These skills must be able to meet both the broad needs of data generators and consumers within the project and the needs of the larger scientific community. Here we describe recommendations for cyberinfrastructure support teams responsible for systems biology research programs. Recommendations are based on lessons learned while establishing and leading a complex, transdisciplinary, host-pathogen malaria systems biology consortium involving many institutions, a variety of disciplines, animal infectious disease models, and clinical studies. While some technical suggestions are included, the primary foci are situational and sociological challenges and tips for handling them.