The characterization of botanical action on the regulation of the metabolic syndrome has been hampered by a lack of systematic approaches in understanding the full extent of affected phenotypes and in fully considering the effects of botanical-diet and botanical-genotype interactions. The Animal Research Core (ARC) will function as an in vivo phenotyping and research arm of the botanical research center using mouse models of metabolic syndrome as an experimental model for biomedical research. The goal of the ARC is to identify key signaling pathways in the development and treatment of the metabolic syndrome that are affected by botanical action, and to work closely with the Botanical Core to test and identify key phytochemical(s) that promote these changes. We will achieve this goal by following three specific aims. One, to work closely with the Center Grant investigators to help design, perform and help analyze data from the animal research phase of the specific projects, and to develop appropriate dosage and toxicological screening to facilitate downstream future clinical studies. Two, because the experimental paradigms differ between the projects, we will develop and utilize a systematic screening and phenotyping approach to facilitate the comparison of different botanicals on the development and treatment of the metabolic syndrome, and to screen for and characterize new and previously unknown new phenotypes affected by botanical action. This will include a characterization of botanical action in the context of defined and differing diets. Three, to take advantage of the classical and molecular genetic expertise of the ARC Project Leader, to design experiments to characterize botanical-genotype interactions in different inbred mouse strains. A major role for the ARC will be to functionally test hypotheses about botanical mechanism of action that emerge from the core investigators laboratories in animal models. We will use specific mutant and transgenic mouse strains that are specifically perturbs in the candidate signaling pathways to confirm or refute the stated hypotheses.
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