The Pilot and Feasibility grant program at the University of Chicago's NIDDK Digestive Diseases Research Core Center (DDRCC) is designed to provide a mechanism to promote new initiatives in digestive diseases (DD)-related research. The overall objectives of this program are to support investigations which would allow the development of preliminary data sufficient for funding of a research grant by conventional mechanisms (pilot studies) or testing of an innovative hypothesis which might have important implications or yield significant results for digestive diseases-related research (feasibility studies). Both of these broad aims have been pursued in the context of research focused on maintenance of homeostasis and an understanding of the pathobiology that accompanies intestinal inflammation. In the previous renewal (2005-10), 25 P & F projects were awarded, and in the current period (2010-14), 26 were awarded. The return on investment (ROI) over the past 10 years has exceeded 25:1, in comparison to the previous period from 1995-2004 where the ROI was 20:1. The P & F program remains an important vehicle for promoting multidisciplinary collaboration and a strong supportive scientific network for the young investigators funded by this program. Track I (new) investigators are given highest priority, followed by Tract II (non-DD) and Tract III (DD, new direction) investigators. We are requesting continuing support at the level of $110,000 per year. The funds will be combined with the $50,000 per year in supplemental funding committed by the GI section, bringing the total award amount to $160,000 or $30,000-37,500 for each award depending on the number of awards selected by the External Advisory Board. With the increased award size, the P & F awards are far more attractive to potential applicants and substantial enough to improve the odds that they will be successful in obtaining independent federal and extramural funding. A key feature of the program is the multi-disciplinary nature of the submitted proposals, coming from numerous departments, programs, and institutional affiliate within the University of Chicago network including the two of the University of Chicago affiliates, Argonne National Laboratory (ANL) and Marine Biological Laboratory (MBL). This large catchment of investigator talent reflects the overall scientific diversity of the research base of the DDRCC. The P & F program has therefore made a difference for many investigators, fostered collaboration and interaction, pushed the envelope of scholarship and discovery, and is one of the jewels of our DDRCC program.