New biologic knowledge will come from both sole investigators following their vision and from teams of scientists sharing their expertise. Some complex biomedical problems require a multidisciplinary vantage point to discover an innovative solution. This Funding Opportunity Announcement (FOA) invites grant applications for investigator-initiated Research Program Project Grant (P01) renewal (Type 2) applications. The P01 program project award supports research that has multiple distinct but synergistic projects built around a unifying central theme within the scientific mission of the NIDDK. The P01 is one of several grant mechanisms the NIDDK uses to foster multi-disciplinary, collaborative research projects. More information on and a comparison among these collaborative grant mechanisms supported by NIDDK can be found at: https://www.niddk.nih.gov/research-funding/process/apply/funding-mechanisms/collaborative-grants-comparison. A central theme or well-defined major objective is the foundation of a P01 program project. Compared to the narrower thrust of a traditional R01 research project, a program project is directed toward a range of scientific questions that elucidate various aspects of the central theme. The interrelationships of research projects and collaborations among investigators will yield synergy and results beyond those achievable if each research project were to be pursued independently. In addition, one or more shared research cores are required. The project leaders and core leaders should be established investigators with strong records of innovative research and independent funding support. The participation of experts in several disciplines or in several areas of one discipline will greatly enhance the goals of the program project. All investigators must contribute to, and share in, the responsibilities of fulfilling the program objectives.