OVERALL PROJECT SUMMARY Limited regeneration of damaged organs and tissues in humans leads to chronic disease and degeneration, while in many invertebrates and lower vertebrates, cellular regeneration repairs and preserves tissue function throughout the lifespan. COBRE Phases I and II Comparative Biology of Tissue Repair, Regeneration and Aging, played a central role in establishing the Kathryn W. Davis Center for Regenerative Biology and Aging (Davis Center) at the MDI Biological Laboratory (MDIBL) as a leading institute in Comparative Biology. The Davis Center was founded on the principle that comparative studies of diverse animal models would lead to a mechanistic understanding of tissue and organ regeneration and identify key points of intervention to improve regeneration in human tissues. In addition, Davis Center research has focused on mechanisms of aging using multiple organisms to learn how cellular anabolic and catabolic pathways may be linked to extension of healthspan. Comparative studies such as these provide a screening platform and rational foundation for development of regenerative medicine therapies, including small molecule drug candidates capable of stimulating tissue regeneration and slowing or reversing aging-induced degenerative changes in patients. COBRE Phases I and II supported eight early-career Project Leaders and one mid-career Project Leader. Six Project Leaders graduated with major independent grant support and the most recent COBRE recruit, Prayag Murawala, has achieved significant professional success and is on a path to independent R01 support. Past and current COBRE Project Leaders have achieved multiple professional milestones in publications, grants, patents, new disease models and research tools, and formation of an IDeA program/Maine state government partnership that allowed MDIBL to obtain $3M in voter-approved state bond funding to expand research infrastructure. COBRE Phase III will continue to build the research infrastructure of the Davis Center by establishing self- sustaining core facilities and funding pilot programs in Aging and Regeneration research. Essential core services will be provided to COBRE graduates, MDIBL investigators, visiting scientists, pilot project awardees, MDIBL course participants from INBRE network institutions, and investigators in Northeast region (NER) IDeA states. Pilot project funding and imaging technology access grants will be made available to all investigators in NER IDeA states. COBRE Phase III will greatly enhance the development of the Davis Center and MDIBL, which in turn will ensure the continued enhancement of the biomedical research environment in Maine.

OVERALL PROJECT NARRATIVE Research in the Davis Center is uniquely focused on using diverse animal models to define the cellular and molecular mechanisms of tissue regeneration and aging, and on translating that information into new regenerative medicine therapies and improvements to healthspan. This Phase III COBRE proposal will transition state of the art core facilities at MDIBL in comparative animal models, bioinformatics and data science, and light microscopy to self-sustainability and support a pilot project program in aging and regenerative biology which will enable MDIBL investigators, visiting scientists, pilot project awardees, and MDIBL course participants to build highly competitive research programs. Core support will consolidate the progress made after hiring, promoting, and retaining successful COBRE investigators in the MDIBL Davis Center and building this Center into a leading research institute in Comparative Biology.