IntBIO: Functional genomic dissection of biomineralization at multiple scales using a new marine model

生物体可以将生物矿物质转化为精致的形状和大小（例如，硅藻，贝壳，骨骼，牙齿，珊瑚礁），其材料特性无法在实验室中模仿。令人惊讶的是，人们对生物矿化的“规则”知之甚少。它在地球上已经进化了50多次，这表明不同的生物已经发现了自己产生这些分子的方法。所涉及的蛋白质独立进化，但彼此具有一些共同特征，从而为了解结构-功能特性提供了机会。本研究利用非生物矿化的海洋无脊椎动物（海葵Nematostella vectensis）的有利特性，利用物理、化学和生物学方法了解生物矿化的细胞和分子方面。一个由不同科学家组成的团队将测试生物矿化理论，并产生新的形状和化合物。这些知识将使工程师能够创造自然界中不存在的新化合物，并从中产生可用于从生物医学到环境工程等领域的结构，从而为生物经济做出贡献。生物矿化是所有年龄的学生感兴趣的一个迷人的主题。该项目的进展将被纳入盖恩斯维尔的惠特尼和北佛罗里达大学的教育活动中。生物矿化过程在许多分类群中是独立演化的。已知在调节矿化反应中起作用的“内在无序蛋白”（IDPs）存在于不同的分类群中，如珊瑚、棘皮动物、海绵和脊椎动物，但它们并不同源，因此为了解IDPs的关键结构和功能特征提供了独特的机会。总体目标是开发一个新的平台，用于在分子，细胞，组织和有机体水平上检查生物矿化的控制。该平台以软体海葵“Starlet”为基础，Nematostella vectensis（刺胞纲，珊瑚虫纲），通过基因编程将IDPs分泌到设计基质和室中，从而研究它们在促进生物矿化过程中的非经典矿化过程中的作用。我们的协作、跨学科和多机构团队提供的综合方法包括比较和功能基因组学、生物化学和蛋白质组学。细胞工程将确定IDPs的翻译后修饰如何影响它们与支架蛋白和矿物前体离子的相互作用。这一结果将有助于研究细胞-基质和细胞-细胞相互作用，这些相互作用涉及产生IDPs分泌到受控“反应空间”所需的极化，这些人工诱导的生物矿物IDPs的结构和功能能力将通过监测矿物前体产生的“矿物学特征”及其与设计基质的相互作用来研究。最后，利用基因组编辑技术，我们将尝试将一个软体生物改造成一个产生珊瑚样外骨骼组件的生物。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Living organisms can transform biominerals into exquisite shapes and sizes (e.g., diatoms, shells, bones, teeth, coral reefs) with material properties that cannot be mimicked in the lab. Surprisingly little is known about the “rules” of biomineralization. That it has evolved on Earth over 50 times indicates that different organisms have discovered their own ways to generate these molecules. The proteins involved evolved independently but share some common features with one another thereby providing an opportunity to understand structure-function properties. This work utilizes the favorable properties of a non-biomineralizing marine invertebrate (the starlet sea anemone Nematostella vectensis) to understand the cellular and molecular aspects of biomineralization utilizing physical, chemical and biological approaches. A diverse team of scientists will test theories of biomineralization, and generate novel shapes and compounds. This knowledge will enable engineers to create novel compounds not seen in nature and generate structures from that could be used in areas from biomedicines to environmental engineering, thereby contributing to the bioeconomy. Biomineralization is a fascinating subject of interest students of all ages. Progress on this project will be incorporated into educational activities at Whitney, in Gainesville, and at the University of North Florida.The process of biomineralization has evolved independently in numerous taxa. The “intrinsically disordered proteins” (IDPs) known to play a role in modulating the mineralization reaction are found in disparate taxa such as corals, echinoderms, sponges, and vertebrates, yet are not homologous thereby providing a unique opportunity to understand key structural and functional features of IDPs. The overarching goal is to develop a novel platform for examining biomineralization at the molecular, cellular, tissue, and organismal levels of control. This platform is based on the soft bodied "Starlet" sea anemone, Nematostella vectensis (Cnidaria, Anthozoa), which will be genetically programmed to secrete IDPs into designer matrices and compartments, enabling examination of their role in promoting non-classical mineralization processes involved in biomineralization. Integrated approaches enabled by our collaborative, interdisciplinary, and multi-institutional team include comparative and functional genomics, biochemistry and proteomics. Cellular engineering will identify how post translational modification of IDPs affect their interaction with scaffolding proteins and mineral precursor ions. This result will enable the study of cell-matrix and cell-cell interactions involved in creating the polarization needed for secretion of IDPs into controlled ‘reaction spaces’ and the structure and functional ability of these artificially-induced biomineral IDPs will be studied by monitoring the ‘mineralogical signatures’ created by mineral precursors and their interactions with the designer matrices. Finally, using genome editing techniques, we will attempt to engineer a soft bodied organism into one that produces components of a coral-like exoskeleton.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.