This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project aims to elucidate the molecular nature of the mechanisms involved in the metabolism, storage, accumulation and general biology of selenium in mammals, and its interactions with other metals, metalloids and halogens, to understand the link between these processes and conditions associated with selenium status. This will be achieved by application of a combination of well-established methods and innovative techniques including x-ray spectroscopic and fluorescence microprobe imaging, which are capable of providing chemical and structural information on intact biological samples. Due to the strong relationship that appears to exist between Se mechanism of action and other heavy elements, we will use XAS to gain precise chemical information for not only selenium but also for the copper, zinc and iron (and will investigate the feasibility of studying I) present in cultured cell pellets and tissue samples. The in vitro experiments previously performed by other groups will be repeated, proposed intermediates will be identified using EXAFS and then confirmed XANES spectra will be added to the library used to identify selenium species in vivo. This advance in knowledge will lead to the identification of potentially problematic relationships between selenium and other species (both in vitro chemical associations (e.g. Cu, Fe) and in vivo epidemiological associations e.g. I, Cu, SCN?), but will also aid the rational design of selenium supplements and drugs with improved efficacies.
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