BIOCHEMICAL STUDIES OF SILICEOUS SKELETAL FORMATION: RO

硅质骨骼形成的生物化学研究：RO

• 批准号: 3267990
• 负责人: BENJAMIN E VOLCANI
• 金额: $ 14.64万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1975
• 资助国家: 美国
• 起止时间: 1975-05-01 至 1988-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3267990
• 关键词: DNA directed DNA polymerase; active transport; autoradiography; cell wall; chemical structure; chemical synthesis; complementary DNA; cyclic AMP; cyclic GMP; electron microscopy; gene expression; genetic manipulation; genetic transcription; germanium; ion transport; ionophores; marine biology; membrane structure; molecular cloning; nucleic acid sequence; plasmids; radiotracer; regulatory gene; silicates; sodium; yeasts

Silicon (Si) is essential for bone formation, and participates in several other metabolic processes in mammals; in diatoms it is essential for cellular metabolism including synthesis of cAMP and DNA; as asbestors and in dusts, Si is the causative agent in fibrotic lung diseases and cancer. Despite its importance, however, research on Si biochemistry is in its infancy, due in part to inherent methodological difficulties. Using the diatom as a paradigm has overcome many of the obstacles and yielded very consequential data on the regulatory role of Si in this organism. The proposed research will extend our studies on Si metabolism, regulation of gene expression, and mineralization in vivo: (i) Characterization of silicate ionophores will be completed and their relation to the silicate transport carrier and other intracellular processes will be determined. In addition, studies on their chemical structure and synthesis of compounds with ionophoretic activity will be carried out. This will not only greatly extend our knowledge of Si transport but could also provide a means of creating totally Si-free media, essential for biological Si- research. (ii) Recombinant DNA techniques will be used to isolate and characterize Si-responsive genes as to response pattern, presence and DNA sequence of regulatory regions, and function. In addition, these techniques will be applied to our studies of Si-regulation of DNA replication. (iii) In our continuing electron microscope studies, the morphological forms of silica in structurally complex cell walls will be examined; the occurrence of an organic matrix in the cell wall will be investigated; and distribution of intramembrane particles in the silicalemma during silica deposition will be determined. The presence of an organic matrix and its relation to silica deposition could radically change present concepts of the diatom cell wall, suggest morphological resemblance to bone matrix, and contribute to our knowledge of bone formation and its Si requirements. In view of Si's importance as both a metabolite and a pathogenic agent, any increases in our knowledge of its mode of action at the molecular level is valuable input to health-related research.

硅（SI）对于骨形成至关重要，参与了几个 哺乳动物的其他代谢过程；在硅藻中，这对于 细胞代谢，包括cAMP和DNA的合成；作为白菜和 在尘埃中，SI是纤维化肺部疾病和癌症中的病因。 但是，尽管它的重要性，但对SI生物化学的研究仍在 婴儿期，部分归因于固有的方法论上的困难。 使用 硅藻作为范式已经克服了许多障碍，并产生了非常非常 有关SI在该生物体中的调节作用的结果数据。 这 拟议的研究将扩展我们对SI代谢的研究，调节 基因表达和体内矿化：（i）表征 硅酸盐离子载体将完成，它们与硅酸盐的关系 将确定运输载体和其他细胞内过程。 在 此外，研究其化合物的化学结构和合成 将进行离子循环活性。 这不仅会很大 扩展我们对SI运输的了解，但也可以提供 创建完全无SI的媒体，对生物学研究至关重要。 （ii）重组DNA技术将用于隔离和表征 Si响应基因关于响应模式，存在和DNA序列 监管区域和功能。 此外，这些技术将是 应用于我们对DNA复制的SI调节研究。 （iii）在我们的 持续电子显微镜研究，二氧化硅的形态形式 将检查在结构复杂的细胞壁中；发生的 将研究细胞壁中的有机基质；和分布 二氧化硅沉积期间硅质中的膜内颗粒将是 决定。 有机基质的存在及其与二氧化硅的关系 沉积可以从根本上改变硅藻细胞壁的当前概念， 暗示形态相似与骨基质，并为我们的 了解骨形成及其SI要求。 鉴于SI的 重要性是代谢物和致病剂，任何增加 我们对其在分子层面的行动方式的了解很有价值 与健康相关研究的输入。