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Biological systems have sophisticated protective mechanisms against a wide array of toxins and xenobiotics. In multicellular organisms, various protective mechanisms form an integrated, homeostatic control system that guides chemoprotection at levels of intra and intercellular transport, metabolism, and behavior. While these mechanisms protect organisms against toxins, they also limit therapeutic drug delivery. Our lab studies the chemical protection processes manifest by cellular systems like the blood brain barrier in the context of intact animals. Using genetic and chemical screens in flies and worms we are dissecting the complex physiology of chemoprotection and devising strategies for improved drug transport to protected spaces.