Ascidian Transferrins and the Evolution of Metal Trafficking

该奖项是与分子和细胞生物科学部(MCB)共同资助的生命过程化学(CLP)项目，支持耶鲁大学安·瓦伦丁教授开展海鞘转铁蛋白基础研究的工作。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。在含有氧气的环境中，铁对生物体来说尤其难以控制，因为它往往会形成不溶的氧化铁(例如，铁锈)。海鞘藻能从海水中隔离出显著浓度的金属离子，因此可能为金属离子管理提供有价值的经验。它们落在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，与脊椎动物中发现的转铁蛋白相似(但非常不同)，它们可能共同作用来管理铁和其他金属离子。这项工作将探索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。总之，这些研究将提供关于在有氧环境中如何进化能力来管理非常难溶的金属离子的经验教训，并将为铁和其他金属的运输提供线索。这项研究涉及无机和生物无机化学、生物地球化学(包括环境中的微量元素循环)、发育生物学以及生物和蛋白质进化。研究活动将与化学推广活动相结合，并将继续为准备程度低于平均水平、但仍可能对大学理工科专业感兴趣的大一新生开发一门化学入门课程。

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.