The O’Halloran laboratory focuses on how the discovery of soluble metal receptor proteins, the pathways they participate in, and the mechanisms by which they regulate cellular events and the physiology of the organism. While calcium and phosphate-relay systems are prime examples of the way biology uses inorganic agents for crucial signaling pathways, several recent discoveries point to the existence of transition metal-based signaling pathways. Early results led the group to discard established doctrines, including the perception that zinc, copper and iron are so-called trace elements that are freely available in the cell. Using multiple cross-disciplinary approaches, this work demonstrated that copper, zinc and iron are abundant cellular players but are not free or readily available within the cell: in unstimulated cells, baseline levels of free zinc, like free calcium, are negligible. Thus, cellular physiology is poised for the stimulated or coordinated release of these metal ions. The O’Halloran research group adopts a highly interdisciplinary approach using the tools of chemistry, molecular biology, structural biology and fluorescence microscopy to elucidate the chemical mechanisms, protein structures, biochemistry and physiological roles of these metal receptors.