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

IntBIO：使用新的海洋模型对多尺度生物矿化进行功能基因组解剖

• 批准号: 2314456
• 负责人: Mark Martindale
• 金额: $ 205.72万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2314456&HistoricalAwards=false
• 关键词: IntBIO; Functional; genomic; dissection; biomineralization

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.

活的生物体可以将生物矿物转变成精致的形状和大小（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，这表明不同的生物体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，但彼此共享一些共同特征，从而提供了了解结构-功能特性的机会。 这项工作利用非生物矿化海洋无脊椎动物（星海葵Nematostella vectensis）的有利特性，利用物理，化学和生物方法来了解生物矿化的细胞和分子方面。一个多元化的科学家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出自然界中未见的新型化合物，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段的学生感兴趣的一个迷人的主题。这个项目的进展将被纳入惠特尼、盖恩斯维尔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独立地进化。已知在调节矿化反应中起作用的“内在无序蛋白”（IDP）在不同的分类群如珊瑚、棘皮动物、海绵和脊椎动物中发现，但不是同源的，从而提供了理解IDP的关键结构和功能特征的独特机会。总体目标是开发一种新的平台，用于在分子，细胞，组织和生物体水平上检查生物矿化。该平台基于软体“Starlet”海葵，Nematostella vectensis（刺胞动物门，珊瑚虫门），其将被遗传编程以将IDP分泌到设计基质和隔室中，从而能够检查它们在促进生物矿化中涉及的非经典矿化过程中的作用。通过我们的协作，跨学科和多机构团队实现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IDP的翻译后修饰如何影响它们与支架蛋白和矿物质前体离子的相互作用。这一结果将使细胞-基质和细胞-细胞相互作用的研究，参与创造所需的极化分泌的IDPs到控制的“反应空间”和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的“矿物学签名”创建的矿物前体和它们与设计师矩阵的相互作用进行研究。最后，利用基因组编辑技术，我们将尝试将一种软体生物改造成一种能产生珊瑚状外骨骼组件的生物。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。