OVERALL ABSTRACT The long-term goal of this Center for Biomedical Research Excellence (COBRE) is to help grow the burgeoning biomedical research industry in Maine by positioning the University of Maine (UMaine) as a biomedical research and training hub that supports and recruits outstanding junior faculty while strengthening our unique statewide graduate program. This COBRE is focused on Regulation of Cellular Behavior in Response to Extracellular Cues. All cells interpret and respond to their environment, yet the mechanisms by which cells process signaling inputs and parse them into discrete cell behaviors are not fully understood. How does G protein coupled receptor signaling regulate polarity in different cell types? How does the extracellular environment regulate muscle cell behaviors such as migration and regeneration? How do viruses modify cells to cause disease? Five research projects led by early career investigators from UMaine and Mount Desert Island Biological Laboratory (MDIBL) will address cell-microenvironmental signaling across three contexts : mechanisms of viral infection in cultured cells and zebrafish; gradient tracking in yeast, and mechanisms of muscle homeostasis in zebrafish. The five research projects are: Cellular reprogramming in Persistent versus Lytic JC Viral Infections (Maginnis); Motility and Guidance Signals Control Migration of Muscle Precursors (Talbot); Mechanisms of GPCR-induced Autophagy (Kelley); Apelin Signaling in Muscle Regeneration (Madeleine), and Innate Immune Function in Influenza-Associated Myopathy (King). Each project leverages the unique expertise of research project leaders while advancing the theme of extracellular impacts on cell behavior. Projects exploit existing IDeA resources and the proposed new core facility in Microscopy and Image Analysis. This COBRE further enhances partnerships among biomedical research institutions in Maine. As director of a state-wide graduate program with 54 graduate students and >150 faculty, Dr. Henry has the leadership experience to guide this COBRE. This COBRE will accelerate the careers of our Junior Investigators by adding: external senior scientists as mentors, state-of-the art live imaging, image analytics, and an expanded zebrafish facility to strengthen the biomedical research infrastructure. UMaine is the only institution in the state that grants doctoral degrees in biomedical science and biomedical engineering. This COBRE, which will be UMaine’s first, will transform UMaine’s ability to serve as the academic leader for biomedical research in Maine and feed the growing biomedical research industry in Maine. This research will elucidate basic biological mechanisms underlying cell behavior, and also has the potential to inform future treatment of infectious diseases, neuromuscular disorders, and muscle aging and regeneration.