Research Project
10177034
Project Summary The biology of multicellular organisms is coordinated across multiple size scales, from the sub-nanoscale of molecules to the macroscale, to tissue-wide interconnectivity of cell populations in complex tissues, organs, and organisms. Using new, state-of-the-art light-sheet fluorescence microscopy (LSFM) and optical clearing (CLARITY) of tissues, current animal models of development, dysfunction, and disease can be appreciated with innovative insights gained only when microscopic analyses (individual cells) are observed and analyzed over macroscopic distances (intact tissues, organs, organisms). This proposal represents a shared request from various NIH-funded researchers at the University of Nebraska Medical Center (UNMC) and surrounding research institutions (Creighton University, Boys Town National Research Hospital) to obtain funding for imaging, tissue processing, and data integration equipment, the Miltenyi UltraMicroscope II, X-Clarity Tissue Hydrogel Polymerization and Clearing System, and data integration workstation not currently available in Nebraska. This type of micro- to macro-scale imaging is of paramount importance for the diverse array of animal studies conducted by cancer biologists, neuroscientists, cell biologists, physiologists, and developmental biologists at UNMC and surrounding institutions. Of the many basic, translational and clinical research centers and programs at UNMC, this proposal will principally serve three focus areas, 1) Cancer (Fred and Pamela Buffett Cancer Center), 2) Neuroscience (Center for Integrative and Translational Neuroscience), and 3) Preclinical drug development and discovery (multiple basic, translational, and clinical researchers aligned with affiliated Nebraska Medicine Hospital and clinics). The proposed instrument cluster led by Dr. Jensen Smith (19 years of biomedical imaging experience) with oversight provided by an advisory committee consisting of Directors of affiliated imaging cores, will provide a robust opportunity to support the strong user base of 17 NIH-funded researchers. We have combined the foundational elements for developing a novel, holistic/multimodal imaging pipeline at UNMC merging structural/anatomical data (MRI, SPECT/CT, Ultrasound, LSFM) with functional and molecular data (intravital optical imaging, photo-acoustics, multiphoton and advanced microscopy) to expand and elevate the rigor of ongoing studies using animal models to understand human disease. In addition to strong user support and demand, the current proposal has strong institutional, inter- and intra-institutional support. As part of a multimodal continuum of animal imaging technologies, the UltraMicroscope II and associated equipment will provide powerful perspectives of various biological phenomena thereby accelerating translational studies aimed at prevention and treatment of human diseases including, neurological function/dysfunction, cancer, and drug development/discovery.
