Biochemical and biophysical elucidation of lanthanide sorting by proteins of the lanthanome

Project Summary Recent efforts have established the first roles of lanthanide ions in biology. These ions, previously not understood to have a biological role, have been shown to serve essential catalytic and functional purposes. Particularly owing to increased use of lanthanide ions in health applications for imaging and therapeutics, the discovery of biological function comes with a need to understand criteria governing the selection, transport, and utilization of these ions. Unlike main-group and transition metal ions, whose selection and use in biology has been much more thoroughly explored, lanthanide ions have comparatively similar properties to one another. Therefore, understanding the mechanisms by which bacteria sort and transport lanthanides contributes to the growing field of lanthanobiology, but can also add a new perspective to the general study of cellular metal ion trafficking, an essential biological process. I plan to address gaps in understanding of lanthanide recognition and uptake in bacteria through studies aimed at the role of protein-lanthanide and protein-protein interactions in the trafficking of lanthanide ions. These studies will contribute to a strengthened foundational understanding of protein-lanthanide interactions and the contributions of these interactions to the selectivity of lanthanide ion transport in biological systems. The proposed research will take place in the laboratory of Prof. Joseph A. Cotruvo, Jr. at Pennsylvania State University (Penn State). The high level of collaborative research in bioinorganic chemistry at Penn State will afford access to both broad technical knowledge in the study of biological metals and career mentorship in the field. Additionally, I have found many opportunities for continued training in teaching and research mentorship in line with my goal of doing research at a primarily undergraduate institution. Along with Prof. Cotruvo’s expertise in the discovery and characterization of lanthanide-binding proteins, these resources and the proposed research will expand my knowledge of and prepare me for a career in bioinorganic chemistry in addition to advancing understanding of lanthanide ions’ role in biology.