Ascidian Transferrins and the Evolution of Metal Trafficking

生命过程化学（CLP）计划中的这一奖项，与分子和细胞生物科学（MCB）部门共同资助，支持耶鲁大学Ann Valentine教授的工作，对海鞘中的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，但在许多情况下有毒。 铁在含氧环境中对生物体特别难以控制，因为它倾向于形成不溶性氧化铁（例如，锈）。海鞘从海水中螯合显著浓度的金属离子，因此可以在金属离子管理方面提供有价值的经验。 它们属于无脊椎动物和脊椎动物之间的进化边界。 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有关（但非常不同），它们可能共同作用以管理铁和其他金属离子。 本工作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。总之，这些研究将提供有关如何在有氧环境中进化管理非常难溶的金属离子的能力的经验教训，并将提供铁和其他金属的运输线索。 该研究位于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），发育生物学以及有机体和蛋白质进化的交叉点。 研究活动将与化学外联活动相结合，并继续为准备低于平均水平但可能对科学和工程专业感兴趣的大一新生开发介绍性化学课程。

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.