Copper is an essential trace nutrient critical to human health. As a prominent cofactor in metalloproteins, it is required to support many fundamental biological functions, including respiration, superoxide detoxification, degradation of amines, and the mobilization and uptake of iron. Cellular copper levels are tightly controlled through a complex network of membrane transporters, chaperone proteins, ligands, and transcription factors. If placed in the wrong environment, copper may catalyze the production of hydroxyl radicals and other reactive oxygen species, a common deleterious mechanism that has profound implications in neurodegenerative diseases (ALS and Alzheimer?s disease) and diseases associated with copper mistrafficking (Menkes and Wilson?s disease). As the pathological conditions are often caused by the toxicity of mislocalized copper rather than the failure to deliver copper to cuproenzymes, detailed knowledge of the copper interactions within the cellular proteome is of fundamental importance. The goal of the parent grant application is to develop molecular tools that will allow researchers to dissect and discover new copper trafficking pathways, both under normal physiological conditions and their alterations in diseases associated with copper dyshomeostasis. In this equipment supplement application, the acquisition of an integrated LC-ICP-MS system is requested for the precise and rapid quantification of trace elements in a broad range of samples and specimens. The instrument will address current shortcomings of elemental quantification by TXRF, which hampers quantitative robustness and lacks high-throughput capabilities required for analyzing chromatographic separations. In a broader context, the research project is expected to be of critical importance for the long-term development of novel diagnostic and therapeutic methods to combat copper-related human diseases.
Copper is an essential trace nutrient critical to human health. A significant number of diseases, including Wilson disease, Menkes syndrome, or Alzheimer?s disease, are caused by impaired copper transport and regulation. The goal of this project is to create molecular tools that will enable the elucidation of copper trafficking pathways in these diseases, and thus support the development of novel diagnostic and therapeutic approaches that will aid in combating copper-related human diseases.
