Ascidian Transferrins and the Evolution of Metal Trafficking

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This award in the Chemistry of Life Processes (CLP) program, co-funded with the Division of Molecular and Cellular Biosciences (MCB), supports work by Professor Ann Valentine at Yale University to carry out fundamental studies on transferrin proteins from the ascidian Ciona intestinalis. Transferrin proteins manage iron, which is vital for most life forms, yet is toxic under many conditions. Iron is particularly difficult for organisms to control in environments that contain oxygen because it tends to form insoluble iron oxides (e.g., rust). Ascidians sequester remarkable concentrations of metal ions from seawater, and thus may offer valuable lessons in metal ion management. They fall on the evolutionary boundary between invertebrates and vertebrates. Ascidians have two different transferrin proteins, related to (but very different from) the ones found in vertebrates, which may work together to manage iron and other metal ions. This work will probe the structure and function of these two ascidian transferrin proteins, as well as the interactions between them.Taken together, these studies will offer lessons about how the capacity evolved to manage very insoluble metal ions in an aerobic environment, and will provide clues to the trafficking of iron and other metals. This inquiry sits at the intersection of inorganic and bioinorganic chemistry, biogeochemistry (including trace element cycling in the environment), developmental biology, and organism and protein evolution. Research activities will be integrated with chemistry outreach and with the continued development of an introductory chemistry course for freshman with less-than-average preparation who may nonetheless be interested in university majors in the sciences and engineering.