09/26/14 Core C: Abstract The Radiobiological Standardization Core provides support for in vitro and in vivo assays for all four projects within the CMCR. In particular, the core will provide animal models for total body irradiation mitigators delivered both by intravenous route and by topical biodegradable microneedle arrays (MNAs). The core will provide male and female mice of the indicated strain, which is C57BL/6, obtained from the same vendor that has been used over the past 10 years (C57BL/6NHsd) as well as Taconic Farms mice (C57BL/6NTac). In addition, mouse strains will be provided for testing the effect of new radiation mitigators on vulnerable populations including: pregnant female mice with timed pregnancies, Fancd2-/- (Fanconi Anemia) mice, and mice for combined injury experiments including traumatic brain injury (control cortical impact) and total body irradiation, and a second model of unicortical bone wounding and total body irradiation. Mice will be held for 2 years for evaluation of long-term effects including carcinogenesis and cognitive behavioral defects. The core will provide for Project 1 all animals for in vivo experiments. For Project 2 (Valerian Kagan, Ph.D., P.I.), the core will provide animal models for fluorescent neutrophil migration into tissues, measured in collaboration with Core G (Watkins), and also will provide mice for evaluation of cardiolipin-lipid signaling pathways as targets for new radiation mitigators to be tested after total body irradiation in vivo. For Project 3 (Hulya Bayir, M.D., P.I.), the core will provide animals for testing anti-necroptosis factors and anti-ferroptosis factors developed through the drug discovery process in that project. For Project 4 (Jian Yu, Ph.D., P.I.), the core will provide assays for intestinal stem cell compared to stem cell niche/intestinal crypt interaction with stem cells using fluorochrome labeled and radiolabeled drugs, as well as cell specific uptake of radiation mitigators drugs detected by HPLC and other methodology in Core F (Yulia Tyurina, Ph.D., P.I.). In addition, the Radiobiological Standardization Core will provide numerous cell lines for measurement of in vitro radiation mitigation. These include human cell line, SHHMT, and murine cell line, 32D cl 3. The Radiobiological Standardization Core has a continuing and intense investigation into the methodology for minimizing the number of animals used to obtain statistical significance, and this collaboration includes frequent interactions with Core D Biostatistics (Hong Wang, Ph.D., P.I.).
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