Ascidian Transferrins and the Evolution of Metal Trafficking

该奖项由生命过程化学（CLP）项目与分子和细胞生物科学部（MCB）共同资助，支持耶鲁大学安·瓦伦丁教授对海鞘转铁蛋白进行基础研究。转铁蛋白管理铁，铁对大多数生命形式至关重要，但在许多情况下是有毒的。在含氧环境中，铁对生物体来说尤其难以控制，因为它往往会形成不溶性的氧化铁（例如铁锈）。海鞘从海水中吸收了大量的金属离子，因此可能为金属离子管理提供宝贵的经验。它们处于无脊椎动物和脊椎动物的进化边界上。海鞘有两种不同的转铁蛋白，与脊椎动物中的转铁蛋白相关（但又非常不同），它们可能共同作用来管理铁和其他金属离子。本研究将探讨这两种海鞘转铁蛋白的结构和功能，以及它们之间的相互作用。综上所述，这些研究将提供关于在有氧环境中如何进化出管理非常不溶性金属离子的能力的教训，并将为铁和其他金属的贩运提供线索。这一研究涉及无机化学和生物无机化学、生物地球化学（包括环境中的微量元素循环）、发育生物学、有机体和蛋白质进化等领域。研究活动将与化学拓展和持续发展的化学入门课程相结合，这些课程是为那些准备程度低于平均水平但可能对大学科学和工程专业感兴趣的大一新生开设的。

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.